secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
2
BRONCHIAL ASTHMAPHARMACOLOGY AND RECENT ADVANCES
Dr Pranesh PawaskarFYR
Dept Of Pharmacology
LTMMC SION MUMBAI - 400022
DATE -13082016
3
4
DEFINITION
Bronchial asthma is a chronic inflammatory airway disease in which
inflammatory agents causing reversible and periodic airway constriction
leading to symptoms like wheeze cough breathlessness chest tightness
etc
5
HISTORY Bronchial asthma was recognized in ancient
Egypt and was treated by drinking an incense mixture
known as Kyphi
Bronchial asthma was officially named as specific
respiratory disorder by Hippocrates in 450 BC
Epinephrine was first referred to in the treatment of
asthma in 1905
Oral corticosteroids began to be used for this
condition in the 1950s while inhaled corticosteroids
and selective Short Acting Beta Agonist came into
wide use in the 1960s
6
EPIDEMIOLOGY
7
EPIDEMIOLOGY
bull The most recent revised global estimate of asthma suggests that as
many as 334 million people have asthma and that the burden of
disability is high
bull Approximately 250000 people die per year from the disease
bull Recognized as a major public health problem since the 1970s
8
RISK FACTORS
9
10
11
STATUS ASTHMATICUS
12
13
14
HISTOPATHOLOGY
bull Bronchi filled with mucus bull Normal vs asthmatic bronchiole
15
SPIROMETRYbull Spirometry is the single best test for asthma
bull If the FEV1 measured by this technique improves more than
12 following administration of a bronchodilator such
as salbutamol this is supportive of the diagnosis
bull Single-breath diffusing capacity can help differentiate asthma
from COPD
16
OTHER TESTS
bull METHACHOLINE CHALLENGE TEST Involves the inhalation of increasing
concentrations of a substance that causes airway narrowing in those
predisposed
bull If negative it means that a person does not have asthma if positive however
it is not specific for the disease
bull PEAK EXPIRATORY FLOW RATE Is variable than spirometry hence not
recommended for diagnosis
17
TYPES OF BRONCHIAL ASTHMA
Intrinsic Asthma
bull It tends to be perennial
bull Status asthmaticus is more
common
Extrinsic Asthma
bull It is mostly episodic
bull Less prone to status asthmaticus
18
DIFFERENTIAL DIAGNOSIS
19
CLASSIFICATION
bull The National Asthma Education And Prevention (NAEP) program has
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
3
4
DEFINITION
Bronchial asthma is a chronic inflammatory airway disease in which
inflammatory agents causing reversible and periodic airway constriction
leading to symptoms like wheeze cough breathlessness chest tightness
etc
5
HISTORY Bronchial asthma was recognized in ancient
Egypt and was treated by drinking an incense mixture
known as Kyphi
Bronchial asthma was officially named as specific
respiratory disorder by Hippocrates in 450 BC
Epinephrine was first referred to in the treatment of
asthma in 1905
Oral corticosteroids began to be used for this
condition in the 1950s while inhaled corticosteroids
and selective Short Acting Beta Agonist came into
wide use in the 1960s
6
EPIDEMIOLOGY
7
EPIDEMIOLOGY
bull The most recent revised global estimate of asthma suggests that as
many as 334 million people have asthma and that the burden of
disability is high
bull Approximately 250000 people die per year from the disease
bull Recognized as a major public health problem since the 1970s
8
RISK FACTORS
9
10
11
STATUS ASTHMATICUS
12
13
14
HISTOPATHOLOGY
bull Bronchi filled with mucus bull Normal vs asthmatic bronchiole
15
SPIROMETRYbull Spirometry is the single best test for asthma
bull If the FEV1 measured by this technique improves more than
12 following administration of a bronchodilator such
as salbutamol this is supportive of the diagnosis
bull Single-breath diffusing capacity can help differentiate asthma
from COPD
16
OTHER TESTS
bull METHACHOLINE CHALLENGE TEST Involves the inhalation of increasing
concentrations of a substance that causes airway narrowing in those
predisposed
bull If negative it means that a person does not have asthma if positive however
it is not specific for the disease
bull PEAK EXPIRATORY FLOW RATE Is variable than spirometry hence not
recommended for diagnosis
17
TYPES OF BRONCHIAL ASTHMA
Intrinsic Asthma
bull It tends to be perennial
bull Status asthmaticus is more
common
Extrinsic Asthma
bull It is mostly episodic
bull Less prone to status asthmaticus
18
DIFFERENTIAL DIAGNOSIS
19
CLASSIFICATION
bull The National Asthma Education And Prevention (NAEP) program has
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
4
DEFINITION
Bronchial asthma is a chronic inflammatory airway disease in which
inflammatory agents causing reversible and periodic airway constriction
leading to symptoms like wheeze cough breathlessness chest tightness
etc
5
HISTORY Bronchial asthma was recognized in ancient
Egypt and was treated by drinking an incense mixture
known as Kyphi
Bronchial asthma was officially named as specific
respiratory disorder by Hippocrates in 450 BC
Epinephrine was first referred to in the treatment of
asthma in 1905
Oral corticosteroids began to be used for this
condition in the 1950s while inhaled corticosteroids
and selective Short Acting Beta Agonist came into
wide use in the 1960s
6
EPIDEMIOLOGY
7
EPIDEMIOLOGY
bull The most recent revised global estimate of asthma suggests that as
many as 334 million people have asthma and that the burden of
disability is high
bull Approximately 250000 people die per year from the disease
bull Recognized as a major public health problem since the 1970s
8
RISK FACTORS
9
10
11
STATUS ASTHMATICUS
12
13
14
HISTOPATHOLOGY
bull Bronchi filled with mucus bull Normal vs asthmatic bronchiole
15
SPIROMETRYbull Spirometry is the single best test for asthma
bull If the FEV1 measured by this technique improves more than
12 following administration of a bronchodilator such
as salbutamol this is supportive of the diagnosis
bull Single-breath diffusing capacity can help differentiate asthma
from COPD
16
OTHER TESTS
bull METHACHOLINE CHALLENGE TEST Involves the inhalation of increasing
concentrations of a substance that causes airway narrowing in those
predisposed
bull If negative it means that a person does not have asthma if positive however
it is not specific for the disease
bull PEAK EXPIRATORY FLOW RATE Is variable than spirometry hence not
recommended for diagnosis
17
TYPES OF BRONCHIAL ASTHMA
Intrinsic Asthma
bull It tends to be perennial
bull Status asthmaticus is more
common
Extrinsic Asthma
bull It is mostly episodic
bull Less prone to status asthmaticus
18
DIFFERENTIAL DIAGNOSIS
19
CLASSIFICATION
bull The National Asthma Education And Prevention (NAEP) program has
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
5
HISTORY Bronchial asthma was recognized in ancient
Egypt and was treated by drinking an incense mixture
known as Kyphi
Bronchial asthma was officially named as specific
respiratory disorder by Hippocrates in 450 BC
Epinephrine was first referred to in the treatment of
asthma in 1905
Oral corticosteroids began to be used for this
condition in the 1950s while inhaled corticosteroids
and selective Short Acting Beta Agonist came into
wide use in the 1960s
6
EPIDEMIOLOGY
7
EPIDEMIOLOGY
bull The most recent revised global estimate of asthma suggests that as
many as 334 million people have asthma and that the burden of
disability is high
bull Approximately 250000 people die per year from the disease
bull Recognized as a major public health problem since the 1970s
8
RISK FACTORS
9
10
11
STATUS ASTHMATICUS
12
13
14
HISTOPATHOLOGY
bull Bronchi filled with mucus bull Normal vs asthmatic bronchiole
15
SPIROMETRYbull Spirometry is the single best test for asthma
bull If the FEV1 measured by this technique improves more than
12 following administration of a bronchodilator such
as salbutamol this is supportive of the diagnosis
bull Single-breath diffusing capacity can help differentiate asthma
from COPD
16
OTHER TESTS
bull METHACHOLINE CHALLENGE TEST Involves the inhalation of increasing
concentrations of a substance that causes airway narrowing in those
predisposed
bull If negative it means that a person does not have asthma if positive however
it is not specific for the disease
bull PEAK EXPIRATORY FLOW RATE Is variable than spirometry hence not
recommended for diagnosis
17
TYPES OF BRONCHIAL ASTHMA
Intrinsic Asthma
bull It tends to be perennial
bull Status asthmaticus is more
common
Extrinsic Asthma
bull It is mostly episodic
bull Less prone to status asthmaticus
18
DIFFERENTIAL DIAGNOSIS
19
CLASSIFICATION
bull The National Asthma Education And Prevention (NAEP) program has
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
6
EPIDEMIOLOGY
7
EPIDEMIOLOGY
bull The most recent revised global estimate of asthma suggests that as
many as 334 million people have asthma and that the burden of
disability is high
bull Approximately 250000 people die per year from the disease
bull Recognized as a major public health problem since the 1970s
8
RISK FACTORS
9
10
11
STATUS ASTHMATICUS
12
13
14
HISTOPATHOLOGY
bull Bronchi filled with mucus bull Normal vs asthmatic bronchiole
15
SPIROMETRYbull Spirometry is the single best test for asthma
bull If the FEV1 measured by this technique improves more than
12 following administration of a bronchodilator such
as salbutamol this is supportive of the diagnosis
bull Single-breath diffusing capacity can help differentiate asthma
from COPD
16
OTHER TESTS
bull METHACHOLINE CHALLENGE TEST Involves the inhalation of increasing
concentrations of a substance that causes airway narrowing in those
predisposed
bull If negative it means that a person does not have asthma if positive however
it is not specific for the disease
bull PEAK EXPIRATORY FLOW RATE Is variable than spirometry hence not
recommended for diagnosis
17
TYPES OF BRONCHIAL ASTHMA
Intrinsic Asthma
bull It tends to be perennial
bull Status asthmaticus is more
common
Extrinsic Asthma
bull It is mostly episodic
bull Less prone to status asthmaticus
18
DIFFERENTIAL DIAGNOSIS
19
CLASSIFICATION
bull The National Asthma Education And Prevention (NAEP) program has
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
7
EPIDEMIOLOGY
bull The most recent revised global estimate of asthma suggests that as
many as 334 million people have asthma and that the burden of
disability is high
bull Approximately 250000 people die per year from the disease
bull Recognized as a major public health problem since the 1970s
8
RISK FACTORS
9
10
11
STATUS ASTHMATICUS
12
13
14
HISTOPATHOLOGY
bull Bronchi filled with mucus bull Normal vs asthmatic bronchiole
15
SPIROMETRYbull Spirometry is the single best test for asthma
bull If the FEV1 measured by this technique improves more than
12 following administration of a bronchodilator such
as salbutamol this is supportive of the diagnosis
bull Single-breath diffusing capacity can help differentiate asthma
from COPD
16
OTHER TESTS
bull METHACHOLINE CHALLENGE TEST Involves the inhalation of increasing
concentrations of a substance that causes airway narrowing in those
predisposed
bull If negative it means that a person does not have asthma if positive however
it is not specific for the disease
bull PEAK EXPIRATORY FLOW RATE Is variable than spirometry hence not
recommended for diagnosis
17
TYPES OF BRONCHIAL ASTHMA
Intrinsic Asthma
bull It tends to be perennial
bull Status asthmaticus is more
common
Extrinsic Asthma
bull It is mostly episodic
bull Less prone to status asthmaticus
18
DIFFERENTIAL DIAGNOSIS
19
CLASSIFICATION
bull The National Asthma Education And Prevention (NAEP) program has
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
8
RISK FACTORS
9
10
11
STATUS ASTHMATICUS
12
13
14
HISTOPATHOLOGY
bull Bronchi filled with mucus bull Normal vs asthmatic bronchiole
15
SPIROMETRYbull Spirometry is the single best test for asthma
bull If the FEV1 measured by this technique improves more than
12 following administration of a bronchodilator such
as salbutamol this is supportive of the diagnosis
bull Single-breath diffusing capacity can help differentiate asthma
from COPD
16
OTHER TESTS
bull METHACHOLINE CHALLENGE TEST Involves the inhalation of increasing
concentrations of a substance that causes airway narrowing in those
predisposed
bull If negative it means that a person does not have asthma if positive however
it is not specific for the disease
bull PEAK EXPIRATORY FLOW RATE Is variable than spirometry hence not
recommended for diagnosis
17
TYPES OF BRONCHIAL ASTHMA
Intrinsic Asthma
bull It tends to be perennial
bull Status asthmaticus is more
common
Extrinsic Asthma
bull It is mostly episodic
bull Less prone to status asthmaticus
18
DIFFERENTIAL DIAGNOSIS
19
CLASSIFICATION
bull The National Asthma Education And Prevention (NAEP) program has
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
9
10
11
STATUS ASTHMATICUS
12
13
14
HISTOPATHOLOGY
bull Bronchi filled with mucus bull Normal vs asthmatic bronchiole
15
SPIROMETRYbull Spirometry is the single best test for asthma
bull If the FEV1 measured by this technique improves more than
12 following administration of a bronchodilator such
as salbutamol this is supportive of the diagnosis
bull Single-breath diffusing capacity can help differentiate asthma
from COPD
16
OTHER TESTS
bull METHACHOLINE CHALLENGE TEST Involves the inhalation of increasing
concentrations of a substance that causes airway narrowing in those
predisposed
bull If negative it means that a person does not have asthma if positive however
it is not specific for the disease
bull PEAK EXPIRATORY FLOW RATE Is variable than spirometry hence not
recommended for diagnosis
17
TYPES OF BRONCHIAL ASTHMA
Intrinsic Asthma
bull It tends to be perennial
bull Status asthmaticus is more
common
Extrinsic Asthma
bull It is mostly episodic
bull Less prone to status asthmaticus
18
DIFFERENTIAL DIAGNOSIS
19
CLASSIFICATION
bull The National Asthma Education And Prevention (NAEP) program has
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
10
11
STATUS ASTHMATICUS
12
13
14
HISTOPATHOLOGY
bull Bronchi filled with mucus bull Normal vs asthmatic bronchiole
15
SPIROMETRYbull Spirometry is the single best test for asthma
bull If the FEV1 measured by this technique improves more than
12 following administration of a bronchodilator such
as salbutamol this is supportive of the diagnosis
bull Single-breath diffusing capacity can help differentiate asthma
from COPD
16
OTHER TESTS
bull METHACHOLINE CHALLENGE TEST Involves the inhalation of increasing
concentrations of a substance that causes airway narrowing in those
predisposed
bull If negative it means that a person does not have asthma if positive however
it is not specific for the disease
bull PEAK EXPIRATORY FLOW RATE Is variable than spirometry hence not
recommended for diagnosis
17
TYPES OF BRONCHIAL ASTHMA
Intrinsic Asthma
bull It tends to be perennial
bull Status asthmaticus is more
common
Extrinsic Asthma
bull It is mostly episodic
bull Less prone to status asthmaticus
18
DIFFERENTIAL DIAGNOSIS
19
CLASSIFICATION
bull The National Asthma Education And Prevention (NAEP) program has
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
11
STATUS ASTHMATICUS
12
13
14
HISTOPATHOLOGY
bull Bronchi filled with mucus bull Normal vs asthmatic bronchiole
15
SPIROMETRYbull Spirometry is the single best test for asthma
bull If the FEV1 measured by this technique improves more than
12 following administration of a bronchodilator such
as salbutamol this is supportive of the diagnosis
bull Single-breath diffusing capacity can help differentiate asthma
from COPD
16
OTHER TESTS
bull METHACHOLINE CHALLENGE TEST Involves the inhalation of increasing
concentrations of a substance that causes airway narrowing in those
predisposed
bull If negative it means that a person does not have asthma if positive however
it is not specific for the disease
bull PEAK EXPIRATORY FLOW RATE Is variable than spirometry hence not
recommended for diagnosis
17
TYPES OF BRONCHIAL ASTHMA
Intrinsic Asthma
bull It tends to be perennial
bull Status asthmaticus is more
common
Extrinsic Asthma
bull It is mostly episodic
bull Less prone to status asthmaticus
18
DIFFERENTIAL DIAGNOSIS
19
CLASSIFICATION
bull The National Asthma Education And Prevention (NAEP) program has
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
12
13
14
HISTOPATHOLOGY
bull Bronchi filled with mucus bull Normal vs asthmatic bronchiole
15
SPIROMETRYbull Spirometry is the single best test for asthma
bull If the FEV1 measured by this technique improves more than
12 following administration of a bronchodilator such
as salbutamol this is supportive of the diagnosis
bull Single-breath diffusing capacity can help differentiate asthma
from COPD
16
OTHER TESTS
bull METHACHOLINE CHALLENGE TEST Involves the inhalation of increasing
concentrations of a substance that causes airway narrowing in those
predisposed
bull If negative it means that a person does not have asthma if positive however
it is not specific for the disease
bull PEAK EXPIRATORY FLOW RATE Is variable than spirometry hence not
recommended for diagnosis
17
TYPES OF BRONCHIAL ASTHMA
Intrinsic Asthma
bull It tends to be perennial
bull Status asthmaticus is more
common
Extrinsic Asthma
bull It is mostly episodic
bull Less prone to status asthmaticus
18
DIFFERENTIAL DIAGNOSIS
19
CLASSIFICATION
bull The National Asthma Education And Prevention (NAEP) program has
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
13
14
HISTOPATHOLOGY
bull Bronchi filled with mucus bull Normal vs asthmatic bronchiole
15
SPIROMETRYbull Spirometry is the single best test for asthma
bull If the FEV1 measured by this technique improves more than
12 following administration of a bronchodilator such
as salbutamol this is supportive of the diagnosis
bull Single-breath diffusing capacity can help differentiate asthma
from COPD
16
OTHER TESTS
bull METHACHOLINE CHALLENGE TEST Involves the inhalation of increasing
concentrations of a substance that causes airway narrowing in those
predisposed
bull If negative it means that a person does not have asthma if positive however
it is not specific for the disease
bull PEAK EXPIRATORY FLOW RATE Is variable than spirometry hence not
recommended for diagnosis
17
TYPES OF BRONCHIAL ASTHMA
Intrinsic Asthma
bull It tends to be perennial
bull Status asthmaticus is more
common
Extrinsic Asthma
bull It is mostly episodic
bull Less prone to status asthmaticus
18
DIFFERENTIAL DIAGNOSIS
19
CLASSIFICATION
bull The National Asthma Education And Prevention (NAEP) program has
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
14
HISTOPATHOLOGY
bull Bronchi filled with mucus bull Normal vs asthmatic bronchiole
15
SPIROMETRYbull Spirometry is the single best test for asthma
bull If the FEV1 measured by this technique improves more than
12 following administration of a bronchodilator such
as salbutamol this is supportive of the diagnosis
bull Single-breath diffusing capacity can help differentiate asthma
from COPD
16
OTHER TESTS
bull METHACHOLINE CHALLENGE TEST Involves the inhalation of increasing
concentrations of a substance that causes airway narrowing in those
predisposed
bull If negative it means that a person does not have asthma if positive however
it is not specific for the disease
bull PEAK EXPIRATORY FLOW RATE Is variable than spirometry hence not
recommended for diagnosis
17
TYPES OF BRONCHIAL ASTHMA
Intrinsic Asthma
bull It tends to be perennial
bull Status asthmaticus is more
common
Extrinsic Asthma
bull It is mostly episodic
bull Less prone to status asthmaticus
18
DIFFERENTIAL DIAGNOSIS
19
CLASSIFICATION
bull The National Asthma Education And Prevention (NAEP) program has
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
15
SPIROMETRYbull Spirometry is the single best test for asthma
bull If the FEV1 measured by this technique improves more than
12 following administration of a bronchodilator such
as salbutamol this is supportive of the diagnosis
bull Single-breath diffusing capacity can help differentiate asthma
from COPD
16
OTHER TESTS
bull METHACHOLINE CHALLENGE TEST Involves the inhalation of increasing
concentrations of a substance that causes airway narrowing in those
predisposed
bull If negative it means that a person does not have asthma if positive however
it is not specific for the disease
bull PEAK EXPIRATORY FLOW RATE Is variable than spirometry hence not
recommended for diagnosis
17
TYPES OF BRONCHIAL ASTHMA
Intrinsic Asthma
bull It tends to be perennial
bull Status asthmaticus is more
common
Extrinsic Asthma
bull It is mostly episodic
bull Less prone to status asthmaticus
18
DIFFERENTIAL DIAGNOSIS
19
CLASSIFICATION
bull The National Asthma Education And Prevention (NAEP) program has
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
16
OTHER TESTS
bull METHACHOLINE CHALLENGE TEST Involves the inhalation of increasing
concentrations of a substance that causes airway narrowing in those
predisposed
bull If negative it means that a person does not have asthma if positive however
it is not specific for the disease
bull PEAK EXPIRATORY FLOW RATE Is variable than spirometry hence not
recommended for diagnosis
17
TYPES OF BRONCHIAL ASTHMA
Intrinsic Asthma
bull It tends to be perennial
bull Status asthmaticus is more
common
Extrinsic Asthma
bull It is mostly episodic
bull Less prone to status asthmaticus
18
DIFFERENTIAL DIAGNOSIS
19
CLASSIFICATION
bull The National Asthma Education And Prevention (NAEP) program has
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
17
TYPES OF BRONCHIAL ASTHMA
Intrinsic Asthma
bull It tends to be perennial
bull Status asthmaticus is more
common
Extrinsic Asthma
bull It is mostly episodic
bull Less prone to status asthmaticus
18
DIFFERENTIAL DIAGNOSIS
19
CLASSIFICATION
bull The National Asthma Education And Prevention (NAEP) program has
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
18
DIFFERENTIAL DIAGNOSIS
19
CLASSIFICATION
bull The National Asthma Education And Prevention (NAEP) program has
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
19
CLASSIFICATION
bull The National Asthma Education And Prevention (NAEP) program has
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
21
TREATMENT
22
APPROACHES TO TREATMENTbull 1 Prevention of AGAB reaction
bull 2 Neutralisation of IgE
bull 3 Suppression of inflammation
bull 4 Prevention of release of mediators
bull 5 Antagonism of released mediators
bull 6 Blockade of constrictor neurotransmitter
bull 7 Mimicking dilator neurotransmitter
bull 8 Directly acting bronchodilators
23
DRUGS USED FOR ASTHMAbull 1 Bronchodilators
- Beta 2 sympathomimetics
- Methylxanthines
- Anticholinergics
bull 2 Leukotriene antgonists
bull 3 Mast cell stabilizers
bull 4 Corticosteroids
- Systemic
- Inhalational
bull 5 Anti-IgE antibody
24
CLASSIFICATIONSHORT ACTING
bull Short-acting Beta2-adrenoceptor
Agonists (SABA) such as Salbutamol are the first line treatment
bull Anticholinergic Medications such as Ipratropium bromide
bull Older less selective Adrenergic Agonists such as inhaled Epinephrine
LONG ACTING
bull Corticosteroids are most effective treatment available for long-term control
bull Long-acting beta-adrenoceptor agonists (LABA) such as salmeterol and formoterol
bull Leukotriene receptor antagonists (such as montelukast and zafirlukast
bull Mast cell stabilizers such as cromolyn sodium
25
BRONCHODILATORSBETA SYMPATHOMIMETIC -
bull Cause Broncho-dilatation through βeta2 receptor stimulation rarr increased
CAMP formation in bronchial muscle cell rarr relaxation
bull Increased CAMP in mast cells and other inflammatory cells decreases
mediator release
bull Since β2 receptors on inflammatory cells desensitize quickly the contribution
of this action is of short duration(SABA)
bull Mainstay of treatment of reversible airway obstruction
26
bull They are the most effective and fastest acting bronchodilators when
inhaled
bull Selective β2 agonists that are now used in asthma to minimize cardiac
side effects
bull Should be used cautiously in hypertensives ischaemic heart disease
patients and in those receiving digitalis
27
28
>
29
BRONCHODILATORS
30
SALBUTAMOL (ALBUTEROL)-
bull Highly selective BETA-2 agonist ( inhaled is best )
bull Action starts in 5 min And lasts for 2-4 hours
bull Used to abort or terminate asthmatic attacks
bull Dose related side effect muscle tremors
bull Palpitation nervousness throat irritation can also occur
bull Bioavailability 50
bull Oral administration increases risk of side effects
31
OTHER SYMPATHOMIMETICS-
bull Terbutaline similar to salbutamol in properties and use
bull Bambuterol prodrug of terbutaline Release active drug for 24 hours
indicated in nocturnal and chronic bronchial asthma
bull Salmeterol first long acting selective b2 agonist more b2 selective
superior action for COPD patients
bull Formeterol faster action than salmeterol but active for 12 hrs
32
BRONCHODILATORSMETHYLXANTHINES bull Theophylline and compounds extensively used in asthma but
are not first line drugs any more
bull On CNS it acts as stimulant Primarily affect higher centers
bull On CVS it acts as a direct stimulant of heart Increases force of myocardial contractions tachycardia Effect on blood pressure is unpredictable
33
bull On smooth muscles it acts as relaxant primarily on bronchial muscles
bull On kidney they act as mild diuretics
bull They enhance power of skeletal muscles enhance pepsin secretion in stomach
bull They increase BMR slightly also decreases release of histamines from mast cells
34
35
36
THEOPHYLLINE
bull Well absorbed orally
bull Metabolised in liver by demethylation and oxidation by CYP1A2
bull Crosses placenta and is secreted in breast milk
bull Factors needed for dose reduction age (06) CHF (06) pneumonia (04) liver failure(02-04)
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
22
APPROACHES TO TREATMENTbull 1 Prevention of AGAB reaction
bull 2 Neutralisation of IgE
bull 3 Suppression of inflammation
bull 4 Prevention of release of mediators
bull 5 Antagonism of released mediators
bull 6 Blockade of constrictor neurotransmitter
bull 7 Mimicking dilator neurotransmitter
bull 8 Directly acting bronchodilators
23
DRUGS USED FOR ASTHMAbull 1 Bronchodilators
- Beta 2 sympathomimetics
- Methylxanthines
- Anticholinergics
bull 2 Leukotriene antgonists
bull 3 Mast cell stabilizers
bull 4 Corticosteroids
- Systemic
- Inhalational
bull 5 Anti-IgE antibody
24
CLASSIFICATIONSHORT ACTING
bull Short-acting Beta2-adrenoceptor
Agonists (SABA) such as Salbutamol are the first line treatment
bull Anticholinergic Medications such as Ipratropium bromide
bull Older less selective Adrenergic Agonists such as inhaled Epinephrine
LONG ACTING
bull Corticosteroids are most effective treatment available for long-term control
bull Long-acting beta-adrenoceptor agonists (LABA) such as salmeterol and formoterol
bull Leukotriene receptor antagonists (such as montelukast and zafirlukast
bull Mast cell stabilizers such as cromolyn sodium
25
BRONCHODILATORSBETA SYMPATHOMIMETIC -
bull Cause Broncho-dilatation through βeta2 receptor stimulation rarr increased
CAMP formation in bronchial muscle cell rarr relaxation
bull Increased CAMP in mast cells and other inflammatory cells decreases
mediator release
bull Since β2 receptors on inflammatory cells desensitize quickly the contribution
of this action is of short duration(SABA)
bull Mainstay of treatment of reversible airway obstruction
26
bull They are the most effective and fastest acting bronchodilators when
inhaled
bull Selective β2 agonists that are now used in asthma to minimize cardiac
side effects
bull Should be used cautiously in hypertensives ischaemic heart disease
patients and in those receiving digitalis
27
28
>
29
BRONCHODILATORS
30
SALBUTAMOL (ALBUTEROL)-
bull Highly selective BETA-2 agonist ( inhaled is best )
bull Action starts in 5 min And lasts for 2-4 hours
bull Used to abort or terminate asthmatic attacks
bull Dose related side effect muscle tremors
bull Palpitation nervousness throat irritation can also occur
bull Bioavailability 50
bull Oral administration increases risk of side effects
31
OTHER SYMPATHOMIMETICS-
bull Terbutaline similar to salbutamol in properties and use
bull Bambuterol prodrug of terbutaline Release active drug for 24 hours
indicated in nocturnal and chronic bronchial asthma
bull Salmeterol first long acting selective b2 agonist more b2 selective
superior action for COPD patients
bull Formeterol faster action than salmeterol but active for 12 hrs
32
BRONCHODILATORSMETHYLXANTHINES bull Theophylline and compounds extensively used in asthma but
are not first line drugs any more
bull On CNS it acts as stimulant Primarily affect higher centers
bull On CVS it acts as a direct stimulant of heart Increases force of myocardial contractions tachycardia Effect on blood pressure is unpredictable
33
bull On smooth muscles it acts as relaxant primarily on bronchial muscles
bull On kidney they act as mild diuretics
bull They enhance power of skeletal muscles enhance pepsin secretion in stomach
bull They increase BMR slightly also decreases release of histamines from mast cells
34
35
36
THEOPHYLLINE
bull Well absorbed orally
bull Metabolised in liver by demethylation and oxidation by CYP1A2
bull Crosses placenta and is secreted in breast milk
bull Factors needed for dose reduction age (06) CHF (06) pneumonia (04) liver failure(02-04)
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
23
DRUGS USED FOR ASTHMAbull 1 Bronchodilators
- Beta 2 sympathomimetics
- Methylxanthines
- Anticholinergics
bull 2 Leukotriene antgonists
bull 3 Mast cell stabilizers
bull 4 Corticosteroids
- Systemic
- Inhalational
bull 5 Anti-IgE antibody
24
CLASSIFICATIONSHORT ACTING
bull Short-acting Beta2-adrenoceptor
Agonists (SABA) such as Salbutamol are the first line treatment
bull Anticholinergic Medications such as Ipratropium bromide
bull Older less selective Adrenergic Agonists such as inhaled Epinephrine
LONG ACTING
bull Corticosteroids are most effective treatment available for long-term control
bull Long-acting beta-adrenoceptor agonists (LABA) such as salmeterol and formoterol
bull Leukotriene receptor antagonists (such as montelukast and zafirlukast
bull Mast cell stabilizers such as cromolyn sodium
25
BRONCHODILATORSBETA SYMPATHOMIMETIC -
bull Cause Broncho-dilatation through βeta2 receptor stimulation rarr increased
CAMP formation in bronchial muscle cell rarr relaxation
bull Increased CAMP in mast cells and other inflammatory cells decreases
mediator release
bull Since β2 receptors on inflammatory cells desensitize quickly the contribution
of this action is of short duration(SABA)
bull Mainstay of treatment of reversible airway obstruction
26
bull They are the most effective and fastest acting bronchodilators when
inhaled
bull Selective β2 agonists that are now used in asthma to minimize cardiac
side effects
bull Should be used cautiously in hypertensives ischaemic heart disease
patients and in those receiving digitalis
27
28
>
29
BRONCHODILATORS
30
SALBUTAMOL (ALBUTEROL)-
bull Highly selective BETA-2 agonist ( inhaled is best )
bull Action starts in 5 min And lasts for 2-4 hours
bull Used to abort or terminate asthmatic attacks
bull Dose related side effect muscle tremors
bull Palpitation nervousness throat irritation can also occur
bull Bioavailability 50
bull Oral administration increases risk of side effects
31
OTHER SYMPATHOMIMETICS-
bull Terbutaline similar to salbutamol in properties and use
bull Bambuterol prodrug of terbutaline Release active drug for 24 hours
indicated in nocturnal and chronic bronchial asthma
bull Salmeterol first long acting selective b2 agonist more b2 selective
superior action for COPD patients
bull Formeterol faster action than salmeterol but active for 12 hrs
32
BRONCHODILATORSMETHYLXANTHINES bull Theophylline and compounds extensively used in asthma but
are not first line drugs any more
bull On CNS it acts as stimulant Primarily affect higher centers
bull On CVS it acts as a direct stimulant of heart Increases force of myocardial contractions tachycardia Effect on blood pressure is unpredictable
33
bull On smooth muscles it acts as relaxant primarily on bronchial muscles
bull On kidney they act as mild diuretics
bull They enhance power of skeletal muscles enhance pepsin secretion in stomach
bull They increase BMR slightly also decreases release of histamines from mast cells
34
35
36
THEOPHYLLINE
bull Well absorbed orally
bull Metabolised in liver by demethylation and oxidation by CYP1A2
bull Crosses placenta and is secreted in breast milk
bull Factors needed for dose reduction age (06) CHF (06) pneumonia (04) liver failure(02-04)
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
24
CLASSIFICATIONSHORT ACTING
bull Short-acting Beta2-adrenoceptor
Agonists (SABA) such as Salbutamol are the first line treatment
bull Anticholinergic Medications such as Ipratropium bromide
bull Older less selective Adrenergic Agonists such as inhaled Epinephrine
LONG ACTING
bull Corticosteroids are most effective treatment available for long-term control
bull Long-acting beta-adrenoceptor agonists (LABA) such as salmeterol and formoterol
bull Leukotriene receptor antagonists (such as montelukast and zafirlukast
bull Mast cell stabilizers such as cromolyn sodium
25
BRONCHODILATORSBETA SYMPATHOMIMETIC -
bull Cause Broncho-dilatation through βeta2 receptor stimulation rarr increased
CAMP formation in bronchial muscle cell rarr relaxation
bull Increased CAMP in mast cells and other inflammatory cells decreases
mediator release
bull Since β2 receptors on inflammatory cells desensitize quickly the contribution
of this action is of short duration(SABA)
bull Mainstay of treatment of reversible airway obstruction
26
bull They are the most effective and fastest acting bronchodilators when
inhaled
bull Selective β2 agonists that are now used in asthma to minimize cardiac
side effects
bull Should be used cautiously in hypertensives ischaemic heart disease
patients and in those receiving digitalis
27
28
>
29
BRONCHODILATORS
30
SALBUTAMOL (ALBUTEROL)-
bull Highly selective BETA-2 agonist ( inhaled is best )
bull Action starts in 5 min And lasts for 2-4 hours
bull Used to abort or terminate asthmatic attacks
bull Dose related side effect muscle tremors
bull Palpitation nervousness throat irritation can also occur
bull Bioavailability 50
bull Oral administration increases risk of side effects
31
OTHER SYMPATHOMIMETICS-
bull Terbutaline similar to salbutamol in properties and use
bull Bambuterol prodrug of terbutaline Release active drug for 24 hours
indicated in nocturnal and chronic bronchial asthma
bull Salmeterol first long acting selective b2 agonist more b2 selective
superior action for COPD patients
bull Formeterol faster action than salmeterol but active for 12 hrs
32
BRONCHODILATORSMETHYLXANTHINES bull Theophylline and compounds extensively used in asthma but
are not first line drugs any more
bull On CNS it acts as stimulant Primarily affect higher centers
bull On CVS it acts as a direct stimulant of heart Increases force of myocardial contractions tachycardia Effect on blood pressure is unpredictable
33
bull On smooth muscles it acts as relaxant primarily on bronchial muscles
bull On kidney they act as mild diuretics
bull They enhance power of skeletal muscles enhance pepsin secretion in stomach
bull They increase BMR slightly also decreases release of histamines from mast cells
34
35
36
THEOPHYLLINE
bull Well absorbed orally
bull Metabolised in liver by demethylation and oxidation by CYP1A2
bull Crosses placenta and is secreted in breast milk
bull Factors needed for dose reduction age (06) CHF (06) pneumonia (04) liver failure(02-04)
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
25
BRONCHODILATORSBETA SYMPATHOMIMETIC -
bull Cause Broncho-dilatation through βeta2 receptor stimulation rarr increased
CAMP formation in bronchial muscle cell rarr relaxation
bull Increased CAMP in mast cells and other inflammatory cells decreases
mediator release
bull Since β2 receptors on inflammatory cells desensitize quickly the contribution
of this action is of short duration(SABA)
bull Mainstay of treatment of reversible airway obstruction
26
bull They are the most effective and fastest acting bronchodilators when
inhaled
bull Selective β2 agonists that are now used in asthma to minimize cardiac
side effects
bull Should be used cautiously in hypertensives ischaemic heart disease
patients and in those receiving digitalis
27
28
>
29
BRONCHODILATORS
30
SALBUTAMOL (ALBUTEROL)-
bull Highly selective BETA-2 agonist ( inhaled is best )
bull Action starts in 5 min And lasts for 2-4 hours
bull Used to abort or terminate asthmatic attacks
bull Dose related side effect muscle tremors
bull Palpitation nervousness throat irritation can also occur
bull Bioavailability 50
bull Oral administration increases risk of side effects
31
OTHER SYMPATHOMIMETICS-
bull Terbutaline similar to salbutamol in properties and use
bull Bambuterol prodrug of terbutaline Release active drug for 24 hours
indicated in nocturnal and chronic bronchial asthma
bull Salmeterol first long acting selective b2 agonist more b2 selective
superior action for COPD patients
bull Formeterol faster action than salmeterol but active for 12 hrs
32
BRONCHODILATORSMETHYLXANTHINES bull Theophylline and compounds extensively used in asthma but
are not first line drugs any more
bull On CNS it acts as stimulant Primarily affect higher centers
bull On CVS it acts as a direct stimulant of heart Increases force of myocardial contractions tachycardia Effect on blood pressure is unpredictable
33
bull On smooth muscles it acts as relaxant primarily on bronchial muscles
bull On kidney they act as mild diuretics
bull They enhance power of skeletal muscles enhance pepsin secretion in stomach
bull They increase BMR slightly also decreases release of histamines from mast cells
34
35
36
THEOPHYLLINE
bull Well absorbed orally
bull Metabolised in liver by demethylation and oxidation by CYP1A2
bull Crosses placenta and is secreted in breast milk
bull Factors needed for dose reduction age (06) CHF (06) pneumonia (04) liver failure(02-04)
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
26
bull They are the most effective and fastest acting bronchodilators when
inhaled
bull Selective β2 agonists that are now used in asthma to minimize cardiac
side effects
bull Should be used cautiously in hypertensives ischaemic heart disease
patients and in those receiving digitalis
27
28
>
29
BRONCHODILATORS
30
SALBUTAMOL (ALBUTEROL)-
bull Highly selective BETA-2 agonist ( inhaled is best )
bull Action starts in 5 min And lasts for 2-4 hours
bull Used to abort or terminate asthmatic attacks
bull Dose related side effect muscle tremors
bull Palpitation nervousness throat irritation can also occur
bull Bioavailability 50
bull Oral administration increases risk of side effects
31
OTHER SYMPATHOMIMETICS-
bull Terbutaline similar to salbutamol in properties and use
bull Bambuterol prodrug of terbutaline Release active drug for 24 hours
indicated in nocturnal and chronic bronchial asthma
bull Salmeterol first long acting selective b2 agonist more b2 selective
superior action for COPD patients
bull Formeterol faster action than salmeterol but active for 12 hrs
32
BRONCHODILATORSMETHYLXANTHINES bull Theophylline and compounds extensively used in asthma but
are not first line drugs any more
bull On CNS it acts as stimulant Primarily affect higher centers
bull On CVS it acts as a direct stimulant of heart Increases force of myocardial contractions tachycardia Effect on blood pressure is unpredictable
33
bull On smooth muscles it acts as relaxant primarily on bronchial muscles
bull On kidney they act as mild diuretics
bull They enhance power of skeletal muscles enhance pepsin secretion in stomach
bull They increase BMR slightly also decreases release of histamines from mast cells
34
35
36
THEOPHYLLINE
bull Well absorbed orally
bull Metabolised in liver by demethylation and oxidation by CYP1A2
bull Crosses placenta and is secreted in breast milk
bull Factors needed for dose reduction age (06) CHF (06) pneumonia (04) liver failure(02-04)
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
27
28
>
29
BRONCHODILATORS
30
SALBUTAMOL (ALBUTEROL)-
bull Highly selective BETA-2 agonist ( inhaled is best )
bull Action starts in 5 min And lasts for 2-4 hours
bull Used to abort or terminate asthmatic attacks
bull Dose related side effect muscle tremors
bull Palpitation nervousness throat irritation can also occur
bull Bioavailability 50
bull Oral administration increases risk of side effects
31
OTHER SYMPATHOMIMETICS-
bull Terbutaline similar to salbutamol in properties and use
bull Bambuterol prodrug of terbutaline Release active drug for 24 hours
indicated in nocturnal and chronic bronchial asthma
bull Salmeterol first long acting selective b2 agonist more b2 selective
superior action for COPD patients
bull Formeterol faster action than salmeterol but active for 12 hrs
32
BRONCHODILATORSMETHYLXANTHINES bull Theophylline and compounds extensively used in asthma but
are not first line drugs any more
bull On CNS it acts as stimulant Primarily affect higher centers
bull On CVS it acts as a direct stimulant of heart Increases force of myocardial contractions tachycardia Effect on blood pressure is unpredictable
33
bull On smooth muscles it acts as relaxant primarily on bronchial muscles
bull On kidney they act as mild diuretics
bull They enhance power of skeletal muscles enhance pepsin secretion in stomach
bull They increase BMR slightly also decreases release of histamines from mast cells
34
35
36
THEOPHYLLINE
bull Well absorbed orally
bull Metabolised in liver by demethylation and oxidation by CYP1A2
bull Crosses placenta and is secreted in breast milk
bull Factors needed for dose reduction age (06) CHF (06) pneumonia (04) liver failure(02-04)
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
28
>
29
BRONCHODILATORS
30
SALBUTAMOL (ALBUTEROL)-
bull Highly selective BETA-2 agonist ( inhaled is best )
bull Action starts in 5 min And lasts for 2-4 hours
bull Used to abort or terminate asthmatic attacks
bull Dose related side effect muscle tremors
bull Palpitation nervousness throat irritation can also occur
bull Bioavailability 50
bull Oral administration increases risk of side effects
31
OTHER SYMPATHOMIMETICS-
bull Terbutaline similar to salbutamol in properties and use
bull Bambuterol prodrug of terbutaline Release active drug for 24 hours
indicated in nocturnal and chronic bronchial asthma
bull Salmeterol first long acting selective b2 agonist more b2 selective
superior action for COPD patients
bull Formeterol faster action than salmeterol but active for 12 hrs
32
BRONCHODILATORSMETHYLXANTHINES bull Theophylline and compounds extensively used in asthma but
are not first line drugs any more
bull On CNS it acts as stimulant Primarily affect higher centers
bull On CVS it acts as a direct stimulant of heart Increases force of myocardial contractions tachycardia Effect on blood pressure is unpredictable
33
bull On smooth muscles it acts as relaxant primarily on bronchial muscles
bull On kidney they act as mild diuretics
bull They enhance power of skeletal muscles enhance pepsin secretion in stomach
bull They increase BMR slightly also decreases release of histamines from mast cells
34
35
36
THEOPHYLLINE
bull Well absorbed orally
bull Metabolised in liver by demethylation and oxidation by CYP1A2
bull Crosses placenta and is secreted in breast milk
bull Factors needed for dose reduction age (06) CHF (06) pneumonia (04) liver failure(02-04)
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
29
BRONCHODILATORS
30
SALBUTAMOL (ALBUTEROL)-
bull Highly selective BETA-2 agonist ( inhaled is best )
bull Action starts in 5 min And lasts for 2-4 hours
bull Used to abort or terminate asthmatic attacks
bull Dose related side effect muscle tremors
bull Palpitation nervousness throat irritation can also occur
bull Bioavailability 50
bull Oral administration increases risk of side effects
31
OTHER SYMPATHOMIMETICS-
bull Terbutaline similar to salbutamol in properties and use
bull Bambuterol prodrug of terbutaline Release active drug for 24 hours
indicated in nocturnal and chronic bronchial asthma
bull Salmeterol first long acting selective b2 agonist more b2 selective
superior action for COPD patients
bull Formeterol faster action than salmeterol but active for 12 hrs
32
BRONCHODILATORSMETHYLXANTHINES bull Theophylline and compounds extensively used in asthma but
are not first line drugs any more
bull On CNS it acts as stimulant Primarily affect higher centers
bull On CVS it acts as a direct stimulant of heart Increases force of myocardial contractions tachycardia Effect on blood pressure is unpredictable
33
bull On smooth muscles it acts as relaxant primarily on bronchial muscles
bull On kidney they act as mild diuretics
bull They enhance power of skeletal muscles enhance pepsin secretion in stomach
bull They increase BMR slightly also decreases release of histamines from mast cells
34
35
36
THEOPHYLLINE
bull Well absorbed orally
bull Metabolised in liver by demethylation and oxidation by CYP1A2
bull Crosses placenta and is secreted in breast milk
bull Factors needed for dose reduction age (06) CHF (06) pneumonia (04) liver failure(02-04)
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
30
SALBUTAMOL (ALBUTEROL)-
bull Highly selective BETA-2 agonist ( inhaled is best )
bull Action starts in 5 min And lasts for 2-4 hours
bull Used to abort or terminate asthmatic attacks
bull Dose related side effect muscle tremors
bull Palpitation nervousness throat irritation can also occur
bull Bioavailability 50
bull Oral administration increases risk of side effects
31
OTHER SYMPATHOMIMETICS-
bull Terbutaline similar to salbutamol in properties and use
bull Bambuterol prodrug of terbutaline Release active drug for 24 hours
indicated in nocturnal and chronic bronchial asthma
bull Salmeterol first long acting selective b2 agonist more b2 selective
superior action for COPD patients
bull Formeterol faster action than salmeterol but active for 12 hrs
32
BRONCHODILATORSMETHYLXANTHINES bull Theophylline and compounds extensively used in asthma but
are not first line drugs any more
bull On CNS it acts as stimulant Primarily affect higher centers
bull On CVS it acts as a direct stimulant of heart Increases force of myocardial contractions tachycardia Effect on blood pressure is unpredictable
33
bull On smooth muscles it acts as relaxant primarily on bronchial muscles
bull On kidney they act as mild diuretics
bull They enhance power of skeletal muscles enhance pepsin secretion in stomach
bull They increase BMR slightly also decreases release of histamines from mast cells
34
35
36
THEOPHYLLINE
bull Well absorbed orally
bull Metabolised in liver by demethylation and oxidation by CYP1A2
bull Crosses placenta and is secreted in breast milk
bull Factors needed for dose reduction age (06) CHF (06) pneumonia (04) liver failure(02-04)
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
31
OTHER SYMPATHOMIMETICS-
bull Terbutaline similar to salbutamol in properties and use
bull Bambuterol prodrug of terbutaline Release active drug for 24 hours
indicated in nocturnal and chronic bronchial asthma
bull Salmeterol first long acting selective b2 agonist more b2 selective
superior action for COPD patients
bull Formeterol faster action than salmeterol but active for 12 hrs
32
BRONCHODILATORSMETHYLXANTHINES bull Theophylline and compounds extensively used in asthma but
are not first line drugs any more
bull On CNS it acts as stimulant Primarily affect higher centers
bull On CVS it acts as a direct stimulant of heart Increases force of myocardial contractions tachycardia Effect on blood pressure is unpredictable
33
bull On smooth muscles it acts as relaxant primarily on bronchial muscles
bull On kidney they act as mild diuretics
bull They enhance power of skeletal muscles enhance pepsin secretion in stomach
bull They increase BMR slightly also decreases release of histamines from mast cells
34
35
36
THEOPHYLLINE
bull Well absorbed orally
bull Metabolised in liver by demethylation and oxidation by CYP1A2
bull Crosses placenta and is secreted in breast milk
bull Factors needed for dose reduction age (06) CHF (06) pneumonia (04) liver failure(02-04)
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
32
BRONCHODILATORSMETHYLXANTHINES bull Theophylline and compounds extensively used in asthma but
are not first line drugs any more
bull On CNS it acts as stimulant Primarily affect higher centers
bull On CVS it acts as a direct stimulant of heart Increases force of myocardial contractions tachycardia Effect on blood pressure is unpredictable
33
bull On smooth muscles it acts as relaxant primarily on bronchial muscles
bull On kidney they act as mild diuretics
bull They enhance power of skeletal muscles enhance pepsin secretion in stomach
bull They increase BMR slightly also decreases release of histamines from mast cells
34
35
36
THEOPHYLLINE
bull Well absorbed orally
bull Metabolised in liver by demethylation and oxidation by CYP1A2
bull Crosses placenta and is secreted in breast milk
bull Factors needed for dose reduction age (06) CHF (06) pneumonia (04) liver failure(02-04)
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
33
bull On smooth muscles it acts as relaxant primarily on bronchial muscles
bull On kidney they act as mild diuretics
bull They enhance power of skeletal muscles enhance pepsin secretion in stomach
bull They increase BMR slightly also decreases release of histamines from mast cells
34
35
36
THEOPHYLLINE
bull Well absorbed orally
bull Metabolised in liver by demethylation and oxidation by CYP1A2
bull Crosses placenta and is secreted in breast milk
bull Factors needed for dose reduction age (06) CHF (06) pneumonia (04) liver failure(02-04)
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
34
35
36
THEOPHYLLINE
bull Well absorbed orally
bull Metabolised in liver by demethylation and oxidation by CYP1A2
bull Crosses placenta and is secreted in breast milk
bull Factors needed for dose reduction age (06) CHF (06) pneumonia (04) liver failure(02-04)
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
35
36
THEOPHYLLINE
bull Well absorbed orally
bull Metabolised in liver by demethylation and oxidation by CYP1A2
bull Crosses placenta and is secreted in breast milk
bull Factors needed for dose reduction age (06) CHF (06) pneumonia (04) liver failure(02-04)
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
36
THEOPHYLLINE
bull Well absorbed orally
bull Metabolised in liver by demethylation and oxidation by CYP1A2
bull Crosses placenta and is secreted in breast milk
bull Factors needed for dose reduction age (06) CHF (06) pneumonia (04) liver failure(02-04)
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
38
BRONCHODILATORSANTICHOLINERGICS-
bull Cause Broncho dilatation by blocking M3 receptors mediated constricted
tone
bull Act primarily on larger airways which receive vagal innervation
bull Less effective than sympathomimetic
bull When inhaled they are drug of choice for COPD
39
MECHANISM OF ACTION OF ANTICHOLINERGICS
40
IPRATROPIUM BROMIDE-
bull Short acting
bull Patients with COPD (reflex cholinergic tone) and psychogenic asthma responds to these better
bull Combination with sympathomimetics produce marked and longer lasting action
bull Dry mouth respiratory discomfort are the ADRs
TIOTROPIUM BROMIDE-
bull Its longer acting
bull More effective than ipratropium
41
LEUKOTRIENE ANTAGONISTbull Two drugs available
bull Both have similar actions and clinical utility
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
39
MECHANISM OF ACTION OF ANTICHOLINERGICS
40
IPRATROPIUM BROMIDE-
bull Short acting
bull Patients with COPD (reflex cholinergic tone) and psychogenic asthma responds to these better
bull Combination with sympathomimetics produce marked and longer lasting action
bull Dry mouth respiratory discomfort are the ADRs
TIOTROPIUM BROMIDE-
bull Its longer acting
bull More effective than ipratropium
41
LEUKOTRIENE ANTAGONISTbull Two drugs available
bull Both have similar actions and clinical utility
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
40
IPRATROPIUM BROMIDE-
bull Short acting
bull Patients with COPD (reflex cholinergic tone) and psychogenic asthma responds to these better
bull Combination with sympathomimetics produce marked and longer lasting action
bull Dry mouth respiratory discomfort are the ADRs
TIOTROPIUM BROMIDE-
bull Its longer acting
bull More effective than ipratropium
41
LEUKOTRIENE ANTAGONISTbull Two drugs available
bull Both have similar actions and clinical utility
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
41
LEUKOTRIENE ANTAGONISTbull Two drugs available
bull Both have similar actions and clinical utility
secretion vascular permeability and recruitment of eosinophils
bull Given for chronic bronchial asthma
bull Rapid oral absorption liver metabolism and excretion into feces
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
42
bull Side effect like headach and rashes
bull Few case of Chrug-strauss Syndrome have been noted
bull Metabolism occurs by CYP2C9
bull Use cautiously in case of pregnancy lactation and hepatic
impairment
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
43
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
44
MECHANISM OF ACTION
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
45
ZILEUTON-
bull Newer drug
bull It is a 5-LOX inhibitor
bull Blocks LTC4D4 as well as LTB4 synthesis
bull So prevents all LTB induced responses
bull Efficacy is similar to montelukast
bull Hepatotoxic
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
46
MAST CELL STABILIZERSODIUM CROMOGLYCATE-
bull Synthetic chromone derivative
bull Inhibits mast cell degranulation
bull Chemotaxis of inflammatory cells is inhibited
bull It is not a bronchodilator hence cant be used in acute asthma attack
bull Used in bronchial asthma allergic rhinitis allergic conjunctivitis
bull Bronchospasm throat irritation and cough occurs if taken as dry powder
inhalation
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
47
KETOTIFEN-
bull An antihistaminic
bull Blocks H1 and blocks stimulation of immunogenic and inflammatory cells
bull Thus mediator release is reduced
bull Produces sedation
bull Dry mouth dizziness nausea weight gain are side effects
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
48
NEDOCROMIL
bull Nedocromil sodium is a medication considered as mast cell stabilizer which act to prevent wheezing shortness of breath and other breathing problems caused by asthma
bull Nedocromil inhibits the degranulation of mast cells prevents release of histamine and tryptase
bull Prevents the synthesis of prostaglandins and leukotrienes
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
49
>
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
50
MECHANISM OF ACTION
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
51
CORTICOSTEROIDSbull Benefit by reducing bronchial hyperactivity by suppressing inflammation and
mucosal edema
bull They are not bronchodilators
bull Afford more complete and sustained symptomatic relief than bronchodilator Improve airflow reduce exacerbation Influence airway remodelling
bull Increases responsiveness of airway muscles to beta agonists
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
52
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
53
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
54
>
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
55
SYSTEMIC STEROID THERAPY
bull In case of severe chronic asthma not controlled by bronchodilators and inhalational steroids
bull Status asthmaticus acute exacerbation ndash start a high dose of rapidly acting corticosteroids shift to oral therapy 5-7 days after
bull COPD- a short course of 1-3 week
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
56
INHALED STEROIDS
bull High topical and low systemic activity High first pass metabolism
bull Beclomethasone budesonide fluticasone are the examples
bull Indicated in all cases of persistent asthma when inhaled beta agonist are
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
58
bull Drugs used-
bull Beclomethasone dipropionate
bull Budesonide ndash non halogenated steroid
bull Fluticccasone propionate- high potencylonger duration
bull Flunisolide- seasonal and perennial rhinitis
59
ANTI IGE ANTIBODY
OMALIZUMAB-
bull Humanised monoclonal antibody
bull Administered subcutaneously
bull Neutralises free IgE without mast cell activation
bull It is found to reduce exacerbations
bull Resistant bronchial asthma
bull Expensive
bull Reserved for resistant asthma patients
60
61
>
62
PHARMACOTHERAPY
63
64
GINA MANAGEMENT OF BRONCHIAL ASTHMA
65
66
67
68
69
BRONCHIAL ASTHMA IN PREGNANCY
RECENT DRUGS
70
71
72
ARFORMOTEROL
bull Long-acting β2 adrenoreceptor agonist (LABA)
bull Generally indicated for the treatment of chronic obstructive pulmonary disease (COPD)
bull It is the active (rr)-(minus)-enantiomer of formoterol and was approved by the united states food and drug administration (FDA) on october 6 2006
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
59
ANTI IGE ANTIBODY
OMALIZUMAB-
bull Humanised monoclonal antibody
bull Administered subcutaneously
bull Neutralises free IgE without mast cell activation
bull It is found to reduce exacerbations
bull Resistant bronchial asthma
bull Expensive
bull Reserved for resistant asthma patients
60
61
>
62
PHARMACOTHERAPY
63
64
GINA MANAGEMENT OF BRONCHIAL ASTHMA
65
66
67
68
69
BRONCHIAL ASTHMA IN PREGNANCY
RECENT DRUGS
70
71
72
ARFORMOTEROL
bull Long-acting β2 adrenoreceptor agonist (LABA)
bull Generally indicated for the treatment of chronic obstructive pulmonary disease (COPD)
bull It is the active (rr)-(minus)-enantiomer of formoterol and was approved by the united states food and drug administration (FDA) on october 6 2006
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
60
61
>
62
PHARMACOTHERAPY
63
64
GINA MANAGEMENT OF BRONCHIAL ASTHMA
65
66
67
68
69
BRONCHIAL ASTHMA IN PREGNANCY
RECENT DRUGS
70
71
72
ARFORMOTEROL
bull Long-acting β2 adrenoreceptor agonist (LABA)
bull Generally indicated for the treatment of chronic obstructive pulmonary disease (COPD)
bull It is the active (rr)-(minus)-enantiomer of formoterol and was approved by the united states food and drug administration (FDA) on october 6 2006
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
61
>
62
PHARMACOTHERAPY
63
64
GINA MANAGEMENT OF BRONCHIAL ASTHMA
65
66
67
68
69
BRONCHIAL ASTHMA IN PREGNANCY
RECENT DRUGS
70
71
72
ARFORMOTEROL
bull Long-acting β2 adrenoreceptor agonist (LABA)
bull Generally indicated for the treatment of chronic obstructive pulmonary disease (COPD)
bull It is the active (rr)-(minus)-enantiomer of formoterol and was approved by the united states food and drug administration (FDA) on october 6 2006
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
62
PHARMACOTHERAPY
63
64
GINA MANAGEMENT OF BRONCHIAL ASTHMA
65
66
67
68
69
BRONCHIAL ASTHMA IN PREGNANCY
RECENT DRUGS
70
71
72
ARFORMOTEROL
bull Long-acting β2 adrenoreceptor agonist (LABA)
bull Generally indicated for the treatment of chronic obstructive pulmonary disease (COPD)
bull It is the active (rr)-(minus)-enantiomer of formoterol and was approved by the united states food and drug administration (FDA) on october 6 2006
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
63
64
GINA MANAGEMENT OF BRONCHIAL ASTHMA
65
66
67
68
69
BRONCHIAL ASTHMA IN PREGNANCY
RECENT DRUGS
70
71
72
ARFORMOTEROL
bull Long-acting β2 adrenoreceptor agonist (LABA)
bull Generally indicated for the treatment of chronic obstructive pulmonary disease (COPD)
bull It is the active (rr)-(minus)-enantiomer of formoterol and was approved by the united states food and drug administration (FDA) on october 6 2006
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
64
GINA MANAGEMENT OF BRONCHIAL ASTHMA
65
66
67
68
69
BRONCHIAL ASTHMA IN PREGNANCY
RECENT DRUGS
70
71
72
ARFORMOTEROL
bull Long-acting β2 adrenoreceptor agonist (LABA)
bull Generally indicated for the treatment of chronic obstructive pulmonary disease (COPD)
bull It is the active (rr)-(minus)-enantiomer of formoterol and was approved by the united states food and drug administration (FDA) on october 6 2006
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
65
66
67
68
69
BRONCHIAL ASTHMA IN PREGNANCY
RECENT DRUGS
70
71
72
ARFORMOTEROL
bull Long-acting β2 adrenoreceptor agonist (LABA)
bull Generally indicated for the treatment of chronic obstructive pulmonary disease (COPD)
bull It is the active (rr)-(minus)-enantiomer of formoterol and was approved by the united states food and drug administration (FDA) on october 6 2006
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
66
67
68
69
BRONCHIAL ASTHMA IN PREGNANCY
RECENT DRUGS
70
71
72
ARFORMOTEROL
bull Long-acting β2 adrenoreceptor agonist (LABA)
bull Generally indicated for the treatment of chronic obstructive pulmonary disease (COPD)
bull It is the active (rr)-(minus)-enantiomer of formoterol and was approved by the united states food and drug administration (FDA) on october 6 2006
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
67
68
69
BRONCHIAL ASTHMA IN PREGNANCY
RECENT DRUGS
70
71
72
ARFORMOTEROL
bull Long-acting β2 adrenoreceptor agonist (LABA)
bull Generally indicated for the treatment of chronic obstructive pulmonary disease (COPD)
bull It is the active (rr)-(minus)-enantiomer of formoterol and was approved by the united states food and drug administration (FDA) on october 6 2006
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
68
69
BRONCHIAL ASTHMA IN PREGNANCY
RECENT DRUGS
70
71
72
ARFORMOTEROL
bull Long-acting β2 adrenoreceptor agonist (LABA)
bull Generally indicated for the treatment of chronic obstructive pulmonary disease (COPD)
bull It is the active (rr)-(minus)-enantiomer of formoterol and was approved by the united states food and drug administration (FDA) on october 6 2006
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
69
BRONCHIAL ASTHMA IN PREGNANCY
RECENT DRUGS
70
71
72
ARFORMOTEROL
bull Long-acting β2 adrenoreceptor agonist (LABA)
bull Generally indicated for the treatment of chronic obstructive pulmonary disease (COPD)
bull It is the active (rr)-(minus)-enantiomer of formoterol and was approved by the united states food and drug administration (FDA) on october 6 2006
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
RECENT DRUGS
70
71
72
ARFORMOTEROL
bull Long-acting β2 adrenoreceptor agonist (LABA)
bull Generally indicated for the treatment of chronic obstructive pulmonary disease (COPD)
bull It is the active (rr)-(minus)-enantiomer of formoterol and was approved by the united states food and drug administration (FDA) on october 6 2006
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
71
72
ARFORMOTEROL
bull Long-acting β2 adrenoreceptor agonist (LABA)
bull Generally indicated for the treatment of chronic obstructive pulmonary disease (COPD)
bull It is the active (rr)-(minus)-enantiomer of formoterol and was approved by the united states food and drug administration (FDA) on october 6 2006
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
72
ARFORMOTEROL
bull Long-acting β2 adrenoreceptor agonist (LABA)
bull Generally indicated for the treatment of chronic obstructive pulmonary disease (COPD)
bull It is the active (rr)-(minus)-enantiomer of formoterol and was approved by the united states food and drug administration (FDA) on october 6 2006
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
bull It is over 100 times more selective for bronchial muscle than myocardial tissue
bull Was in clinical trials before 2010 when it has been withdrawn from further development based on evidence that the compound does not possess a competitive profile
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
74
INDACATEROL-bull Ultra-long-acting beta-adrenoceptor agonist developed by novartis
bull It needs to be taken only once a day
bull It is delivered as an aerosol formulation through a dry powder inhaler
bull It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD)
bull Long-term data in patients with asthma are thus far lacking
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
bull Olodaterol mimics the effect of epinephrine at β2 receptors in the lung
which causes the bronchi to relax and reduces their resistance to airflow
bull Olodaterol is substantially metabolized by glucuronidation
bull 88 intrinsic activity compared to the gold standard isoprenaline
bull Olodaterol monotherapy was previously evaluated in four phase II studies in
asthma patients Not yet approved for asthma treatment
bull Phase III studies planned for Olodaterol monotherapy in patients with
asthma
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
77
LONG ACTING MUSCARINIC AGONIST- (LAMA)
bull There are emerging data from key clinical trials to show that LAMA may
confer bronchodilator effects and improved control when used in addition
to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-
adrenoceptor agonists (LABA)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
78
NVA237 (GYCOPYRRONIUM)
bull Once-daily dry-powder formulation of the long-acting muscarinic antagonist Glycopyrronium Bromide
bull Glycopyrronium bromide in COPD Airways Clinical Study 1 (GLOW1) evaluated the efficacy safety and tolerability
bull Provided rapid sustained improvements in lung function improvements in dyspnoea and health-related quality of life and reduced the risk of exacerbations and the use of rescue medication
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
79
CILOMILAST-
bull It is orally active and acts as a selective phosphodiesterase-4 inhibitor
bull Four clinical trials were identified evaluating the efficacy of Cilomilast the usual randomized double-blind and placebo-controlled protocols were used
bull Cilomilast is a second-generation PDE4 inhibitor with anti-inflammatory effects that target bronchoconstriction mucus hypersecretion and airway remodelling associated with COPD And bronchial asthma
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
80
bull ROFLUMILAST-
bull Is a drug that acts as a selective long-acting inhibitor of the enzyme
phosphodiesterase-4 (PDE-4)
bull It has anti-inflammatory effects and is used as an orally administered drug for
the treatment of inflammatory conditions of the lungs
bull Its primary clinical use is in the prevention of exacerbations (lung attacks) in
severe COPD
bull Has an inhibitory effect on allergen-induced responses in asthma
bull Side effects - diarrhoea weight decreased nausea headache insomnia
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
81
bull Prostaglandin (PG)D2 is released from mast cells Th2 cells and dendritic
cells and activates DP2-receptors also known as chemoattractant homologous receptor expressed on Th2 cells (CRTh2) which mediate chemotaxis of Th2 cells and eosinophils
bull Many CRTh2 antagonists are now in clinical development for asthma including amg-853 oc000459 and mk-2746 which have shown early clinical efficacy as oral treatments for asthma and rhinitis
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
82
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
83
bull SETIPIPRANT-
bull Is a drug originally developed by Actelion which acts as a selective orally available antagonist of the Prostaglandin D2 receptor 2 (DP2)
bull Initially researched as a treatment for allergies and inflammatory disorders particularly asthma
bull It failed to show sufficient advantages over existing drugs and was discontinued from further development in this application
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
84
bull FEVIPIPRANT-
bull Code name QAW039
bull Drug being developed by novartis which acts as a selective orally available antagonist of the prostaglandin d2 receptor 2 (DP2 or CRTh2)
bull As of 2016 it is in phase II clinical trials for the treatment of asthma
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
85
bull CICLESONIDE-
bull A new ICS that is locally activated in the lower airway epithelium
bull Consequently with very low systemic bioavailability
bull Negligible risk of local or systemic side effects even for long-term high-
dose treatment
bull Cleaved by Esterases in bronchial epithelium
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
86
bull RAMATROBAN
bull Is a thromboxane receptor antagonist
bull It is also a DP2 receptor antagonist
bull It has also been used for the treatment of asthma
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
87
bull MAPRACORAT
bull Anti-inflammatory drug belonging to the experimental class of selective glucocorticoid receptor agonists (SEGRAs)
bull In clinical trials for the topical treatment of atopic dermatitis inflammation following cataract surgery and allergic conjunctivitis
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
88
bull The enzyme 5-lipoxygenase (5-LO) works through 5lo-activating protein (FLAP)
bull Several novel 5-LO and FLAP inhibitors are currently in clinical development
bull Drugs like Meclofenamate Sodium and Zileuton
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
89
CYTOKINE BLOCKADE
bull Inhibition of another th2 cytokine interleukin (IL)-4 by using inhaled soluble receptors proved to be disappointing but there is continued interest in blocking IL-13 a related cytokine that regulates immunoglobulin E (IgE) formation particularly in severe asthma
bull IL-4 and IL-13 signal through stat6 (signal transduction-activated transcription factor) and small molecule inhibitors such as as1517499 have been developed that are active in a murine model of asthma
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
90
PITRAKINRA-
bull A mutated form of IL-4 that blocks IL-4Rα
bull IL -4Rα The common receptor for IL-4 and IL-13 significantly reduces the late response to inhaled allergen in mild asthmatics when given by nebulization
bull Clinical trials are currently in progress
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
91
bull An antibody against the IL-5 receptor (IL-5Rα) is also being studied in clinical trials
bull Inhaled antisense oligonucleotides that block the common β chain of IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors together with the chemokine receptor CCR3 (TPI ASM8) has a small effect in reducing allergen responses and airway inflammation
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
92
bull Several uncontrolled or small studies suggested that anti-TNF therapies (TNF blocking antibody Infliximab or soluble receptor Etanercept) may be useful in reducing symptoms exacerbations and airway hyperresponsiveness in patients with severe asthma
bull a recent large multicentre trial with an antibody Golimumab showed no beneficial effect on lung function symptoms or exacerbations and there were increased reports of pneumonia and cancer
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
93
bull Recently agonists of Bitter taste receptors (TAS2R) including Quinine
Chloroquine And Saccharine have been identified as a novel class of
Bronchodilator
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
94
bull Corticosteroids switch off inflammatory genes by recruiting the nuclear
enzyme histone deacetylase-2 (HDAC2) to the activated inflammatory
gene initiation site
bull So that activators of this enzyme may also have anti-inflammatory effects
or may enhance the anti-inflammatory effects of corticosteroids
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
95
RECENT ADVANCESbull PPARγ AGONISTS
bull Peroxisome proliferator-activated receptor gamma agonists have a wide spectrum of anti-inflammatory effects including inhibitory effects on macrophages T cells and neutrophilic inflammation and polymorphisms of the PPARγ gene have been linked to increased risk of asthma
bull A PPARγ agonist Rosiglitazone gave a small improvement in lung function in smoking asthmatic patients in whom inhaled corticosteroids were ineffective[67] and a modest (15) reduction in late response to inhaled allergen in mild asthmatics
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
96
LUMILIXIMAB -
bull A monoclonal antibody that targets CD23
bull Is well tolerated and reduces IgE concentrations in patients with mild asthma
bull Clinical efficacy has not been reported
bull It is being investigated in phase I and II clinical trials for the treatment of Chronic Lymphocytic Leukemia
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
97
bull Stem cell factor (SCF) is a key regulator of mast cell survival in the airways
bull acts via the receptor c-kit on mast cells
bull blockade of SCF or c-kit is very effective in animal models of asthma
bull suggesting that this pathway may be a good target for new asthma therapies
bull Masitinib is a potent tyrosine kinase inhibitor that blocks c-kit (as well as platelet-derived growth factor receptors) and provides some symptomatic benefit in patients with severe asthma
bull more selective c-kit inhibitors are in development
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
98
bull SPLEEN TYROSINE KINASE (SYK) that is involved in activation of mast cells and other immune cells and several small molecule SYK kinase inhibitors are in development
bull An antisense inhibitor of SYK kinase is effective in an animal model of asthma
bull And the small molecule inhibitor R112 given nasally reduces nasal symptoms in hay fever patients
bull More potent inhibitors such as R343 and Bay 61ndash3606 are in development for inhalation in asthma
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
99
bull New technology for delivering inhaled drugs by metered dose inhaler
bull Using the new hydrofluoroalkane propellant instead of the old
chlorofluorocarbon propellant
bull The modulate technology combines the use of hydrofluoroalkane propellant
(maintaining the drug in a solution that may be better nebulised in ultrafine
particles) and some improvement in the device (with slow plume speed and
better lung penetration)
bull This new formulation has the potential for more effectively reaching the
smaller airways an important target of treatment especially in more severe
asthmatics
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
100
bull The Single-inhaler Maintenance And Reliever Therapy has been
developed
bull A rapid-onset bronchodilator (eg Formoterol) and an ICS (eg
Budesonide) at the time of the occurrence of asthma symptoms allows
the delivery of higher doses of ICS at very beginning stages of
exacerbations
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
101
SOME HOME REMEDIES
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
102
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
103
SOME AYURVEDIC MEDICATIONS
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
104
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
105
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
106
BRONCHIAL THERMOPLASTYbull Bronchial thermoplasty delivered by the ALAIR system
bull Is a treatment for severe asthma approved by the FDA in 2010
bull Involving the delivery of controlled therapeutic radiofrequency energy to the airway wall thus
heating the tissue and reducing the amount of smooth muscle present in the airway wall
bull This treatment has been shown to result in acute epithelial destruction with regeneration
observed in the epithelium blood vessels mucosa and nerves
bull However airway smooth muscle has demonstrated almost no capacity for regeneration
instead being replaced by connective tissue
bull The treatment has been shown to be safe and effective over at least five years
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
107
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
108
Benefits
bull 32 reduction in asthma attacks
bull 84 reduction in emergency room visits for respiratory symptoms
bull 66 reduction in days lost from work school or other daily activities due
to asthma symptoms
bull 73 reduction in hospitalizations for respiratory symptoms
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
109
FINALLYbull Educational activities going around world about Bronchial asthma
bull Development of some implementation plans at the regional or country level have been done
bull New research is on going always Newer medicines are showing good results
bull This all has obtained consistent results in terms of a reduction of the socioeconomic burden of the disease with a high share from the patients associated with improvement in HRQOL and reduction in disability due to asthma
bull Still there is a much longer path to make world asthma free forever
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
110
FAMOUS FACES WITH ASTHMA
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
111
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
112
REFERENCESbull GINA 2011 P 18
bull ASTHMA FACT SHEET Ndeg307 WHO NOVEMBER 2013 ARCHIVED FROM THE ORIGINAL ON JUNE 29 2011 RETRIEVED 3 MARCH2016
bull YAWN BP (SEPTEMBER 2008) FACTORS ACCOUNTING FOR ASTHMA VARIABILITY ACHIEVING OPTIMAL SYMPTOM CONTROL FOR INDIVIDUAL PATIENTSPRIMARY CARE RESPIRATORY JOURNAL 17 (3) 138ndash147 DOI103132PCRJ200800004 PMID 18264646 ARCHIVED FROM THE ORIGINAL (PDF)ON 2010-03-04
bull SCOTT JP PETERS-GOLDEN M (SEPTEMBER 2013) ANTILEUKOTRIENE AGENTS FOR THE TREATMENT OF LUNG DISEASE AM J RESPIR CRIT CARE MED 188 (5) 538ndash544 DOI101164RCCM201301-0023PP
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA
DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67
bull EDITORS ANDREW HARVER HARRY KOTSES (2010) ASTHMA HEALTH AND SOCIETY A PUBLIC HEALTH PERSPECTIVE NEW YORK SPRINGER P 315ISBN 978-0-387-78285-0
bull ENVIRONMENTAL EPIGENETICS AND ASTHMA CURRENT CONCEPTS AND CALL FOR STUDIES AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
bull HENDERSON AJ SHAHEEN SO (MAR 2013) ACETAMINOPHEN AND ASTHMA PAEDIATRIC RESPIRATORY REVIEWS 14 (1) 9ndash15 QUIZ 16DOI101016JPRRV201204004
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
113
REFERENCESbull TAN DJ WALTERS EH PERRET JL LODGE CJ LOWE AJ MATHESON MC DHARMAGE SC (FEBRUARY 2015)
AGE-OF-ASTHMA ONSET AS A DETERMINANT OF DIFFERENT ASTHMA PHENOTYPES IN ADULTS A SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE EXPERT REVIEW OF RESPIRATORY MEDICINE 9 (1) 109ndash23 DOI1015861747634820151000311
bull CUSTOVIC A SIMPSON A (2012) THE ROLE OF INHALANT ALLERGENS IN ALLERGIC AIRWAYS DISEASE JOURNAL OF INVESTIGATIONAL ALLERGOLOGY amp CLINICAL IMMUNOLOGY OFFICIAL ORGAN OF THE INTERNATIONAL ASSOCIATION OF ASTHMOLOGY (INTERASMA) AND SOCIEDAD LATINOAMERICANA DE ALERGIA E INMUNOLOGIA 22 (6) 393ndash401 QIUZ FOLLOW 401 PMID 23101182
bull RAMSEY CD CELEDOacuteN JC (JANUARY 2005) THE HYGIENE HYPOTHESIS AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 11 (1) 14ndash20DOI10109701MCP000014579113714AE
bull OBER C HOFFJAN S (2006) ASTHMA GENETICS 2006 THE LONG AND WINDING ROAD TO GENE DISCOVERY GENES IMMUN 7 (2) 95ndash100DOI101038SJGENE6364284
bull BEUTHER DA (JANUARY 2010) RECENT INSIGHT INTO OBESITY AND ASTHMA CURRENT OPINION IN PULMONARY MEDICINE 16 (1) 64ndash70DOI101097MCP0B013E3283338FA7
bull SALPETER S ORMISTON T SALPETER E (2002) CARDIOSELECTIVE BETA-BLOCKERS FOR REVERSIBLE AIRWAY DISEASE THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS (4) CD002992 DOI10100214651858CD00299
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
114
REFERENCESbull CHEN E MILLER GE (2007) STRESS AND INFLAMMATION IN EXACERBATIONS OF ASTHMA BRAIN
BEHAV IMMUN 21 (8) 993ndash9DOI101016JBBI20070300
bull BERKART JB (JUNE 1880) THE TREATMENT OF ASTHMA BRITISH MEDICAL JOURNAL 1 (1016) 917ndash8 DOI101136BMJ11016917PMC 2240555
bull BOUSQUET J BOUSQUET PJ GODARD P DAURES JP (JULY 2005) THE PUBLIC HEALTH IMPLICATIONS OF ASTHMA BULLETIN OF THE WORLD HEALTH ORGANIZATION 83 (7) 548ndash54 PMC 2626301
bull WORLD HEALTH ORGANIZATION WHO ASTHMA ARCHIVED FROM THE ORIGINAL ON 15 DECEMBER 2007 RETRIEVED 2007-12-29
bull THE GLOBAL ASTHMA REPORT 2014 RETRIEVED 10 MAY 2016
bull HONDRAS MA LINDE K JONES AP (2005) HONDRAS MA ED MANUAL THERAPY FOR ASTHMA COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2) CD001002 DOI10100214651858CD001002PUB2 PMID 15846609
bull BLANC PD TRUPIN L EARNEST G KATZ PP YELIN EH EISNER MD (2001) ALTERNATIVE THERAPIES AMONG ADULTS WITH A REPORTED DIAGNOSIS OF ASTHMA OR RHINOSINUSITIS DATA FROM A POPULATION-BASED SURVEY CHEST 120 (5) 1461ndash7 DOI101378CHEST12051461PMID 1171312
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
Slide 1
Bronchial asthma pharmacology and recent advances
Slide 3
definition
history
epidemiology
epidemiology (2)
Risk factors
Slide 9
Slide 10
Status asthmaticus
Slide 12
Slide 13
histopathology
spirometry
Other tests
Types of bronchial asthma
Differential diagnosis
classification
Clinical classification
Treatment
Approaches to treatment
Drugs used for asthma
classification (2)
bronchodilators
Slide 26
Slide 27
Slide 28
bronchodilators (2)
Slide 30
Slide 31
bronchodilators (3)
Slide 33
Slide 34
Slide 35
Slide 36
Slide 37
bronchodilators (4)
Mechanism of action of anticholinergics
Slide 40
Leukotriene antagonist
Slide 42
Slide 43
Mechanism of action
Slide 45
Mast cell stabilizer
Slide 47
Slide 48
Slide 49
Mechanism of action (2)
corticosteroids
Slide 52
Slide 53
Slide 54
Systemic steroid therapy
Slide 56
Slide 57
Slide 58
Anti ige antibody
Slide 60
Slide 61
pharmacotherapy
Slide 63
Gina Management of bronchial asthma
Slide 65
Slide 66
Slide 67
Slide 68
Bronchial Asthma in pregnancy
Recent drugs
Slide 71
Slide 72
Slide 73
Slide 74
Slide 75
Slide 76
Slide 77
Slide 78
Slide 79
Slide 80
Slide 81
Slide 82
Slide 83
Slide 84
Slide 85
Slide 86
Slide 87
Slide 88
Slide 89
Slide 90
Slide 91
Slide 92
Slide 93
Slide 94
Recent advances
Slide 96
Slide 97
Slide 98
Slide 99
Slide 100
Some home remedies
Slide 102
Some ayurvedic medications
Slide 104
Slide 105
Bronchial thermoplasty
Slide 107
Slide 108
finally
Famous faces with asthma
Slide 111
references
references (2)
references (3)
references (4)
115
REFERENCES
bull BOULET LP LAVIOLETTE M (MAYndashJUN 2012) IS THERE A ROLE FOR BRONCHIAL THERMOPLASTY IN THE TREATMENT OF ASTHMA CANADIAN RESPIRATORY JOURNAL 19 (3) 191ndash2 DOI1011552012853731 PMC 3418092
bull CATES CJ CATES MJ (APR 18 2012) CATES CHRISTOPHER J ED REGULAR TREATMENT WITH FORMOTEROL FOR CHRONIC ASTHMA SERIOUS ADVERSE EVENTS COCHRANE DATABASE OF SYSTEMATIC REVIEWS 4 CD006923 DOI10100214651858CD006923PUB3
bull FANTA CH (MARCH 2009) ASTHMA NEW ENGLAND JOURNAL OF MEDICINE 360 (10) 1002ndash14 DOI101056NEJMRA0804579PMID 19264689
bull ANANDAN C NURMATOV U VAN SCHAYCK OC SHEIKH A (FEBRUARY 2010) IS THE PREVALENCE OF ASTHMA DECLINING SYSTEMATIC REVIEW OF EPIDEMIOLOGICAL STUDIES ALLERGY 65 (2) 152ndash67 DOI101111J1398-9995200902244X
