bronchial asthma
TRANSCRIPT
Bronchial asthmaBronchial asthmaBy Dr:Ahmad ElmadanaBy Dr:Ahmad Elmadana
DefinitionDefinition
It is a chronic recurrent obstructive disorder of bronchi, characterized by attacks of shortness of breath (muscle spasm, mucosa edema, hypersecretion) and based on genetically determined bronchi hyperreactivity.
EpidemiologyEpidemiology
Asthma is a problem worldwide, with an estimated 300 million affected individuals.
10 million lost school days each year and costing more than $12 billion per year
About 10% school-age children are affected in urban areas
Most frequent respiratory pathology (≈30%)
Morbidity is growing every year
EpidemiologyEpidemiology
African-American children have been affected more frequently than Caucasian children (2:1).
Hospitalization rates also were markedly higher for African-American children (4:1).
Predisposing factorsPredisposing factors
HOST FACTORSGenetic, e.g.,• Genes pre-disposing to atopy• Genes pre-disposing to airway
hyperresponsivenessObesitySex
Predisposing factorsPredisposing factors
ENVIRONMENTAL FACTORSAllergens• Indoor: Domestic mites, furred animals
(dogs, cats, mice), cockroach allergen, fungi, molds, yeasts
• Outdoor: Pollens, fungi, molds, yeasts
Predisposing factorsPredisposing factors
ENVIRONMENTAL FACTORS
Infections (predominantly viral) Occupational sensitizersTobacco smoke• Passive smoking• Active smokingOutdoor/Indoor Air PollutionDiet
Genetic predispositionGenetic predisposition
On chromosomes 5q23–31, 11q and 12q. Classical positional cloning approaches have led to identification of new genes of potential importance on chromosome 14q24 and chromosome 20p13 (ADAM33).
Genetic predispositionGenetic predisposition
Multiple gene predisposition instead of one-gene coding
ENVIRONMENTAL FACTORSENVIRONMENTAL FACTORS
Allergic sensitisation to Dermatophagoides pteronyssinus
Passive smokingAir pollutionCow milk feedingFood allergens during 1st year of life
ENVIRONMENTAL FACTORSENVIRONMENTAL FACTORS
Mycoplasma pneumoniaeChlamydia species Respiratory syncytial virus
Treatment with antibiotics appropriate for these organisms improves the clinical signs and symptoms of asthma.
Periods of developmentPeriods of development
1st - inherited predisposition2nd – allergic sensitization3rd – allergic reactions
Examples of Agents Causing Asthma inSelected Occupations
Occupation/occupational field Agent
Animal and Plant Proteins
Bakers Flour, amylase
Fish food manufacturing Midges, parasites
Food processing Coffee bean dust, meat tenderizer, tea, shellfish,amylase, egg proteins, pancreatic enzymes,papain
Organic chemicals
Hospital workers Disinfectants (sulfathiazole, chloramines,formaldehyde, glutaraldehyde), latex
Manufacturing Antibiotics, piperazine, methyldopa, salbutamol,cimetidine
Automobile painting Ethanolamine, dissocyanates
MECHANISMS OF ASTHMAMECHANISMS OF ASTHMA
Mast cells:
activated mucosal mast cells release bronchoconstrictor mediators (histamine,
cysteinyl leukotrienes, prostaglandin D2). These cells are activated by allergens through high-affinity IgE receptors, as well as by osmotic stimuli (accounting for exercise-induced bronchoconstriction). Increased
mast cell numbers in airway smooth muscle may be linked to airway hyperresponsiveness.
MECHANISMS OF ASTHMAMECHANISMS OF ASTHMA
Eosinophils
present in increased numbers in the airways, release basic proteins that may damage airway epithelial cells.They may also have a role in the release of growth factors and airway remodeling.
MECHANISMS OF ASTHMAMECHANISMS OF ASTHMA
T-lymphocytes
present in increased numbers in the airways,release specific cytokines, including IL-4, IL-5,
IL-9, and IL-13, that orchestrate eosinophilic inflammation and IgE production by B lymphocytes. An increase in Th2 cell activity may be due in part to a reduction in regulatory T cells that normally inhibit Th2 cells. There may also be an increase in inKT cells, which release large amounts of T helper 1 (Th1) and Th2 cytokines.
MECHANISMS OF ASTHMAMECHANISMS OF ASTHMA
Dendritic cells
sample allergens from the airway surface and migrate to regional lymph nodes, where they interact with regulatory T cells and ultimately stimulate production of Th2
cells from naive T cells.
MECHANISMS OF ASTHMAMECHANISMS OF ASTHMA
Macrophages
increase in number in the airways and may be activated by allergens through low-affinity IgE receptors to release inflammatory mediators and cytokines that amplify the inflammatory response.
MECHANISMS OF ASTHMAMECHANISMS OF ASTHMA
Neutrophil numbers
are increased in the airways and sputum of
patients with severe asthma and in smoking asthmatics, but the pathophysiological role of these cells is uncertain and their increase may even be due to glucocorticosteroid therapy.
Airway Structural Cells Involved in Airway Structural Cells Involved in thethe Pathogenesis of AsthmaPathogenesis of Asthma
Airway epithelial cells sense their mechanical environment,
express multiple inflammatory proteins in asthma, and release
cytokines, chemokines, and lipid mediators. Viruses and air
pollutants interact with epithelial cells.
Airway Structural Cells Involved in Airway Structural Cells Involved in thethe Pathogenesis of AsthmaPathogenesis of Asthma
Airway smooth muscle cells express similar inflammatory
proteins to epithelial cells101.
Airway Structural Cells Involved in Airway Structural Cells Involved in thethe Pathogenesis of AsthmaPathogenesis of Asthma
Endothelial cells of the bronchial circulation play a role in
recruiting inflammatory cells from the circulation into the airway.
Airway Structural Cells Involved in Airway Structural Cells Involved in thethe Pathogenesis of AsthmaPathogenesis of Asthma
Fibroblasts and myofibroblasts produce connective tissue
components, such as collagens and proteoglycans, that are
involved in airway remodeling.
Airway Structural Cells Involved in Airway Structural Cells Involved in thethe Pathogenesis of AsthmaPathogenesis of Asthma
Airway nerves are also involved. Cholinergic nerves may be activated by reflex triggers in the airways and cause
bronchoconstriction and mucus secretion. Sensory nerves, which may be sensitized by inflammatory stimuli including
neurotrophins, cause reflex changes and symptoms such as cough and chest tightness, and may release inflammatory
neuropeptides.
PATHOPHYSIOLOGYPATHOPHYSIOLOGY
PATHOPHYSIOLOGYPATHOPHYSIOLOGY
PATHOPHYSIOLOGYPATHOPHYSIOLOGY
Sun Ying и соавт., 2006
PATHOPHYSIOLOGYPATHOPHYSIOLOGY
PATHOPHYSIOLOGYPATHOPHYSIOLOGY
3. Allergic reactions3. Allergic reactions
3 phases: ImmunologicPathochemicalPathophysiological
ImmunologicImmunologic
Antibody + Antigen formationComplement involvementAuto-Ab and auto-Ags
PathochemicalPathochemical
Active substances release in “shock” organs (mucous and muscles of bronchi and bronchioli)
PathophysiologicalPathophysiological
Muscle spasmMucous edemaHypersecretion (thick exudate)
Pathogenesis – Pathogenesis – acute asthmaacute asthma
Bronchial smooth muscle contractionMucous gland hypersecretionSubmucosal, peribronchial, and interstitial
edemaCellular infiltrative changes involving
plasma cells, lymphocytes, macrophages, and leukocytes.
Pathogenesis – Pathogenesis – cchronic asthma hronic asthma
Smooth muscle hyperplasiaPostinflammatory thickening of the
bronchial basement membranesMucous gland hypertrophy
PATHOPHYSIOLOGYPATHOPHYSIOLOGY
Symptoms Symptoms of bronchial asthmaof bronchial asthma
Breathlessness Anxiety Cough Chest tightness Diaphoresis Exacerbation with exercise
Signs of bronchial asthmaSigns of bronchial asthma
Barrel chest Global or focal wheezes Pallor Pulsus paradoxus Use of accessory muscles Exercise limitation
BronchodilatorsBronchodilators
Beta-adrenergicMethylxanthineAnticholinergic medications
BBetaeta-2-2-adrenergic-adrenergic
Short-acting:SalbutamolTerbutalinBerotek Long-acting:SelmeterolFormoterol
Nonselective adrenergicNonselective adrenergic
Beta-nonselective:AstmopentAlupentIsadrin NovodrinAlfa-,beta-adrenergic:Adrenalin
MMethylxanthineethylxanthine
EuphillinTeophilllin
AAnticholinergic medicationsnticholinergic medications
AtroventOxyvent
AntiallergicAntiallergic
Cromoglycates and nedocromils:IntalZaditenKetotifen
Other drugsOther drugs
Antibiotics Expectorants
Newer choisesNewer choises
Leukotrien inhibitors:Montelucast, zafirlucast – very low
efficacy Were tested for aspirin-dependent
asthma, asthma of physical stress
Survived? Survived? Any questions? Any questions?