asthma. self study materials for medical students. (in collaboration with zhuravka n.v.)

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AsthmaSelf study materials for students

6th year, Internal Medicine, Pulmonology circleTopic 3-4. Management of patients with asthma

Dr. Natalia ZhuravkaDr. Anton Litvin

Assistant professorsof Internal Medicine

V. N. Karazin Kharkiv National University

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Definition Asthma is a chronic inflammatory disease of the airways which develops under the allergens influence, associates with bronchial hyperresponsiveness and reversible obstruction and manifests with attacks of dyspnea, breathlessness, cough, wheezing, chest tightness and sibilant crackles more expressed at expiration.

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Definition (GINA, 2011)Asthma is a common and potentially

serious chronic disease that can be controlled but not cured

Asthma causes symptoms such as wheezing, shortness of breath, chest tightness and cough that vary over time in their occurrence, frequency and intensity

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Definition (GINA, 2011)Symptoms are associated with variable

expiratory airflow, i.e. difficulty breathing air out of the lungs due to: Bronchoconstriction (airway narrowing) Airway wall thickening Increased mucus

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Definition (GINA, 2011)Symptoms may be triggered or worsened

by factors such as viral infections, allergens, tobacco smoke, exercise and stress

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Epidemiology• About 300 million people worldwide are affected

(1 - 18% of total population)• 250,000 people die per year• Low and middle income countries make up

more than 80% of the mortality • It is more common in developed countries.• Asthma is twice as common in boys as girls• Asthma is more common in the young than the

old

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Epidemiology

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Etiology

• Genes

• Atopy

• Bronchial hyperresponsiveness

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Atopy• Atopy is a predisposition toward developing certain allergic hypersensitivity reactions by excessive production of allergen-specific antibodies (Ig E).• It is genetic origin.• Atopy is the cause of eczema(atopic

dermatitis), allergic rhinitis (hay fever), asthma, allergic conjunctivitis, eosinophilic esophagitis, anaphylaxis.

http://www.biofronttech.com/images/ige.gif

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Bronchial hyperresponsiveness• Bronchial hyperresponsiveness (or other

combinations with airway or hyperreactivity) is a state characterised by easily triggered bronchospasm.

• Bronchial hyperresponsiveness can be assessed with a bronchial challenge test (post bronchodilator test).

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Triggers The most common triggers are:• Allergens• Air pollutants• Smoking• Viral respiratory infection• Hyperventilation• Physical exertion• Emotional stress• Adverse weather conditions

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Allergens The allergens are divided into:• communal• industrial • occupational• natural • pharmacological• alimentary

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Communal allergens Communal allergens are presented by:• house-dust mites which live in carpets,

mattresses and upholstered furniture;• spittle, excrements, desquamated epidermis,

hair and fur of domestic animals;• vital products of domestic insects (e.g.,

cockroach);• mycelial yeast-like fungi (molds);• tobacco smoke during active or passive

smoking;• various communal aerosols and synthetic

detergents.

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Industrial allergens Main industrial allergen is industrial and photochemical smog, which consists of:• Nitric, carbonic, sulfuric oxides• Formaldehyde• Ozone• Emissions of biotechnological industry

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Occupational allergens The most important occupational allergen is the dust of:• Constructed buildings• Mills, weaving-mills• Book depositories• Etc.

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face.jpg

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Natural allergens• Plant pollen (especially ambrosia,

wormwood and goose-foot pollen) • Respiratory (viral) infections

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Pharmacological allergens

• Enzymes• Antibiotics• Vaccines• Serums• Aspyrin• Β-blockers

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Alimentary allergens• Milk• Eggs• Wheat flour• Fish• Meat• Stabilizers• Nuts• Genetically modified products

http://www.datamonitorconsumer.com/files/2014/01/Food1.jpg

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Pathogenesis• Asthma pathogenesis is quite difficult and

insufficiently studied.• In most cases the disease is based on 1 type

hypersensitivity reaction.

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Type 1 hypersensitivity reaction

• Type I hypersensitivity (or immediate hypersensitivity) is an allergic reaction provoked by reexposure to a specific type of antigen referred to as an allergen.

• Exposure may be by ingestion, inhalation, injection, or direct contact.

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Type 1 hypersensitivity reaction• Macrophage meets and absorbs the antigen.• Presentation of antigen to CD4+ T-

helpers cells specific to the antigen that stimulate B-cell production of IgE antibodies also specific to the antigen.

• Normally  IgA, IgG, or IgM being produced.• IgE antibodies bind to receptors on the

surface of tissue mast cells and blood basophils (sensibilisation).

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Type 1 hypersensitivity reaction

• Later exposure to the same allergen cross-links the bound IgE on sensitised cells, resulting in degranulation and the secretion of pharmacologically active mediators such as  histamine, serotonin, chemotaxis factors, heparin, proteases, thromboxane, leukotrienes, prostaglandins that act on the surrounding tissues.

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Type 1 hypersensitivity reaction

The principal effects of these products are:•  vasodilation• smooth-muscle contraction• hyperergic inflammation• mucous edema• glands hypersecretion• viscous exudate formation

http://graphics8.nytimes.com/images/2007/08/01/health/adam/19346.jpg

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Type 1 hypersensitivity reaction

https://www.youtube.com/watch?v=gafekFEbUg4

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Pathogenesis

https://upload.wikimedia.org/wikipedia/commons/4/4a/Asthma_attack-illustration_NIH.jpg

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Microscopic changes• Bronchial wall infiltration with mast

cells, eosinophils, basophils and T-lymphocytes

• Edema of mucous and submucous tunics

• Destruction of bronchial epithelium• Hypertrophy of bronchial smooth

muscles,• Hyperplasy of submucous glands • Microvessels dilation

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Classification• Etiology: ▪ exogenous (atopic) ▪ endogenous (non-atopic)• Clinical course: ▪ intermittent (beginning, early) ▪ persistent (chronic, late)• Phase: ▪ remission ▪ exacerebration

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Classification• Severity:

Clinical course, severity

Daytime asthma symptoms

Nighttime awakenings

FEV1, PEF

Intermittent< 1 /week 2 and < /month >80% predicted.

Daily variability < 20%

Mild persistent 1 /week but

not daily > 2 /month>80% predicted. Daily variability – 20-30%

Moderate persistent

Daily > 1 /week> 60 but < 80% predicted. Variability>30%.

Severe persistent

Persistent, limits normal

activityDaily

<60% predicted. Variability > 30%.

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GINA classification Asthma is classified by GINA on the base of control assessment and divided into:• well-controlled• partially controlled• uncontrolled

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GINA classificationAsthma control is considered as:• daytime symptoms 2 /week;• ability to engage in normal daily activity;• the absence of night-time awakenings as a

result of asthma symptoms;• need in bronchodilators administration

2 /week;• the absence of asthma exacerbations;• normal or near normal lung function

parameters.

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SymptomsClassic sighns of asthma are:• Attacks of expiratory dyspnea• Shortness of breath• Cough• Chest tightness • Wheezing (high-pitched whistling

sounds at expiration) • Sibilant crackles

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Exacerbration It has 3 periods:• Prodromal period• Peak period• Period of reverse changes.

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Prodromal period• Vasomotoric nasal reaction with

profuse watery discharge• Sneezing, dryness in nasopharynx • Paroxysmal cough with viscous

sputum • Emotional lability • Excessive sweating• Skin itch• Other symptoms

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Peak period• Expiratory dyspnea • Forced position with arms support• Poorly productive cough• Cyanotic skin and mucous layers• Hyperexpansion of thorax with use of all accessory

muscles at breathing• Percussion: tympanitis, shifted downward lung borders• Auscultation: diminished breath sounds, sibilant

crackles, prolonged expiration, tachycardia. • Severe exacerbations: the signs of right-sided heart

failure (swollen neck veins, hepatomegalia), overload of right heart chambers on ECG.

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Period of reverse changes• Comes spontaneously or under

pharmacologic therapy• Dyspnea and breathlessness relieve and

disappear • Sputum becomes more liquid• Productive cough• Patient breathes easier• Last from several minutes to hours

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Status asthmaticus• Acute severe asthma (status

asthmaticus) is an acute exacerbation of asthma that lasts for several hours and does not respond to standard treatments of bronchodilators (inhalers) and steroids.

•  It is a life-threatening episode of airway obstruction and is considered a medical emergency.

• Complications include cardiac and/or respiratory arrest.

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Status asthmaticus• Progressive respiratory failure• Hypoxemia• Hypercapnia• Respiratory acidosis• Increased blood viscosity• Blockade of bronchial β2-receptors

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Atypical forms• Episodic appearance of wheezing• Cough, heavy breathing occurring at night• Cough, hoarseness after physical activity• “Seasonal” cough, wheezing, chest tightness

(e.g., during pollen period of ambrosia)• The same symptoms occurring during contact

with allergens, irritants• Lingering course of acute respiratory

infections

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Complications Persistent asthma:• Fibrosing bronchitis • Small bronchi deformation and obliteration • Emphysema • Pneumosclerosis • Chronic respiratory failure • Chronic cor pulmonale.

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Complications Asthma exacerbations:• Pneumothorax• Lung atelectasis• Pneumonia• Acute or subacute cor pulmonale• Asthmatic status.

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Lab diagnostics• TBC - eosinophilia, moderate leucocytosis,

increased ESR.• Immunological tests - increased serum

level of Ig E.• Sputum microscopy - inflammatory cells,

Curschmann's spirals (viscous mucus which copies small bronchi) and Charcot-Leyden crystals (crystallized enzymes of eosinophils and mast cells)

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X-ray• Hyperlucency of lung

fields• Low standing and

limited mobility of diaphragm

• Eexpanded intercostal spaces

• Horizontal rib position

• => Emphysema

http://www.mypacs.net/repos/mpv3_repo/viz/full/0/59/3/61869396.jpg

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Spirometry & Peakflowmetry

• Forced vital capacity (FVC) is the volume of air that can forcibly be blown out after full inspiration, measured in liters. FVC is the most basic maneuver in spirometry tests.

• Forced expiratory volume in 1 second (FEV1) is the volume of air that can forcibly be blown out in one second, after full inspiration.

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Spirometry & Peakflowmetry• FEV1/FVC (FEV1%, Tiffeneau index) is

the ratio of FEV1 to FVC. In healthy adults this should be approximately 75–80%.

• Peak expiratory flow (PEF) is the maximal flow (or speed) achieved during the maximally forced expiration initiated at full inspiration, measured in liters per minute or in liters per second.

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Spirometry & Peakflowmetry

https://www.youtube.com/watch?v=M4C8EInOMOI

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Peakflow meters

https://www.nlm.nih.gov/medlineplus/ency/images/ency/fullsize/19367.jpghttp://www.woodleyequipment.com/images/clinical-trials/big/bg41275650293Peak%20Flow%20Meter.jpg.jpg

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Post bronchodilator test

• Post bronchodilator test – is a performing of peakflowmetry for 2 times: before and after inhaling bronchodilator.

• If the forced vital capacity after inhaling (FVC2) is15% > than FVC1

before inhaling => Ds: Asthma

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Differential diagnosis• In COPD there is permanent damage to the

airways. The narrowed airways are fixed, and so symptoms are chronic (persistent). Treatment to open up the airways, is therefore limited.

• In asthma there is inflammation in the airways which makes the muscles in the airways constrict. This causes the airways to narrow. The symptoms tend to come and go, and vary in severity from time to time. Treatment to reduce inflammation and to open up the airways usually works well.

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Differential diagnosis

• COPD is more likely than asthma to cause a chronic (ongoing) cough with sputum.

• Night time waking with breathlessness or wheeze is common in asthma and uncommon in COPD.

• COPD is rare before the age of 35 while asthma is common in under-35.

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Key to diagnosis• History• Physical exam (resp. tract, skin,

chest)• Spirometry to demonstrate

reversibility• Additional studies

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Acute exacerbation

https://www.youtube.com/watch?v=EK8nzKzdnIM

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Management1. Avoiding the contact with allergen. If it is

impossible, the specific hyposensitization with standard allergens should be performed. It is rather effective in case of monoallergy, in intermittent and mild persistent asthma, in remission phase.

2. Elimination of trigger factors (rational job placement, changing the residence, psychological and physical adaptation, careful drug using) is the second condition for successful asthma treatment.

3. Optimally selected medical care is the base of asthma management.

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Drug therapyAntiinflammatory drugs

(basic) Bronchodilators

Hormone-containing(corticosteroids)

Nonhormone-containing(cromones, leukotriene receptor antagonists)

Anticholinergic drugs

β2-agonists

Methylxanthines

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Drug therapy

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Drug therapy

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CorticosteroidsThe mechanism of action lays in:

• cell membrane stabilization • inhibition of inflammatory mediators• restoring the sensivity of β2-receptors.

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Corticosteroids• Inhaled corticosteroids are the most effective

and safe and considered to be the first line drugs for asthma treatment.

• Systemic are used during short courses, mainly in case of severe persistent asthma or asthmatic status.

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Inhaled steroidsRepresentatives:

• Fluticasone – Flovent, Diskus• Budesonide - Pulmicort• Mometasone – Asmanex, Twisthaler• Beclomethasone - Qvar• Ciclesonide - Alvesco

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• stabilize cell membranes• used mainly in pediatric practice (in childhood) • in case of intermittent or mild persistent asthma

Representatives:• Cromolyn sodium – Intal• Nedocromil – Tilade

Cromones

http://4nrx.ru/tilade-inhaler-nedocromil-sodium.jpghttp://kakzdravie.com/wp-content/uploads/2014/08/intal1.jpg

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Leukotriene receptor antagonists• have the moderate intiinflammatory activity• used in case of aspirin-induced asthma and

asthma of physical exertion.

Representatives:• Montelukast - Singulair• Zafirlukast – Accolate• Zileuton - Zyflo

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• β2-agonists - stimulate β2-adrenergic receptors of bronchi

• Anticholinergic drugs - reduce tonus of vagus

• Methylxanthines - inhibit phosphodiesterase

Bronchodilators

Smooth muscle relaxation

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They are the basic drug group among bronchodilators.

• Short-acting (duration of action 5-6 h) β2-agonists (SABAs) – Salbutamol, Fenoterol - are used for quick relief of asthma symptoms.

• Long-acting (> 12 h) β2-agonists (LABAs) - Salmoterol, Farmoterol - for prevention of asthma symptoms occurring.

Inhaled b2-agonists

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They are used predominantly in nighttime asthma and in elderly patients because of the least cardiotoxic effect.Representatives:

• Ipratropium bromide• Atrovent• Troventol

Anticholinergic drugs

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Combined inhaled drugs (corticosteroids with b2-agonists) with use of delivery devices (nebulasers, turbuhalers, spasers, spinhalers, sinchroners) enhance the effectiveness of asthma therapy.

Representatives:• Seretide• Simbicort

Combined drugs

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Management of asthmatic status• Oxygen• Systemic corticosteroids (Hydrocortisone 200mg or

Methylprednisolone 125mg every 6h or Prednisolone 50 mg/day per os)

• Inhalations of short-acting β2-agonists - Salbutamol 5mg or Fenoterol 2mg through nebulaser – 3 times at 1st hour, then once an hour till distinct improvement of patient’s condition is achieved; then 3-4 times a day.

• Inhaled anticholinergic drugs or Aminophylline IV. • If ineffective - artificial lung ventilation.

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Types of inhalers

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How to use inhaler?

https://www.youtube.com/watch?v=Rdb3p9RZoR4

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Spacer• Spacer is an add-on device used to increase the

ease of administering aerosolized medication from a metered-dose inhaler (MDI).

• The spacer adds space in the form of a tube or “chamber” between the canister of medication and the patient’s mouth, allowing the patient to inhale the medication by breathing in slowly and deeply for five to 10 breaths.

http://www.asthma.ca/images/adults/treatment/spacer.gif

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How to use spacer?

https://www.youtube.com/watch?v=uJy97bTdGzI

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Nebulizer• Nebulizer is a drug delivery device used to administer

medication in the form of a mist inhaled into the lungs.• Nebulizers are commonly used for the treatment

of cystic fibrosis, asthma, COPD and other respiratory diseases.

• Nebulizers use oxygen, compressed air or ultrasonic power to break up medical solutions and suspensions into small aerosol droplets (mist) that can be directly inhaled from the mouthpiece of the device.

http://img.medicalexpo.com/images_me/photo-g/electro-pneumatic-nebulizer-mask-compressor-69408-139473.jpg

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How to use nebulizer?

https://www.youtube.com/watch?v=HGZSCe98CWU

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Prognosis• In case of early detection and adequate

treatment the prognosis for the disease is favourable.

• It becomes serious in severe persistent and poorly controlled (insensitive for corticosteroids)asthma.

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The examination of working capacity• The patients with unfavorable for

the disease conditions of work need the job replacement.

• Physical labours with severe asthma are disable to work.

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Prophylaxis• Preservation of the environment,

healthy life-style (smoking cessation, physical training) – are the basis of primary prophylaxis.

• These measures in combination with adequate drug therapy are effective for secondary prophylaxis.

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Thank you