Bronchial Athma

1. Bronchial Athma Yoon Jung Oh, M.D. The Departments of Pulmonary and Critical care Medicine Ajou University School of Medicine

2. Definition • Variable and reversible airway obstruction • Airway inflammation • Bronchial hyperresponsiveness

3. Characteristics of asthma in 10 points • 1. Episodic paroxysms of wheezy dyspnea • 2. Symptom-free periods • 3. Bronchial hyperresponsiveness • 4. Significant reversibility with beta2 agonists (≥ 20%) • 5. Significant reversibility with steroids (≥ 20%) • 6. Eosinophil inflammation • 7. Airway obstruction or narrowing: • Increased resistance to airflow • Reduced ventilatory capacity of obstructive type • 8. Rapid and considerable changes in lung function • (peak flow variation ≥ 20%) • 9. Frequent nocturnal episodes and low morning peak flow values • 10.Frequent occurrence of allergy

4. Prevalence and Classification • 4~5% of the population • Before age 10 (50%), Before age 30 (30%) • Childhood M : F = 2:1, Age 30 M : F = 1:1 Age Personal or family history of allergic diseases Skin test IgE level Idiosyncratic asthma < age 3 or > age 35 absent Negative normal Allergic asthma Age 3 ~ 35 Present Positive increased

5. Pathogenesis of Asthma (1) • Inflammatory changes in the bronchi • The bronchial wall, its basement membrane and muscle layer are • thickened. • There is accumulation and activation of eosinophils. • There is shedding of ciliated epithelium. • clusters of epithelial cells(Creola bodies). • The mucociliary clearance is grossly impaired. • Extensive mucus plugging occludes the lumen. • The lungs are hyperinflated with small atelectatic areas.

6. Normal adult Smooth muscle Mucous membrane mucus Muscular spasm Sticky mucus Mucosal edema Expiratory pressure

7. Pathogenesis of asthma (2) • Airway inflammation • : bronchoconstriction, vascular congestion, edema formation • Macrophages(antigen presenting cell) • Mast cells • Primary mediator : histamine, serotonine, ECF-A • Secondary mediator : LT(B,C,D,E), PGs(E2,F2,D2),bradykinin, PAF • Eosinophils (major basic protein, eosinophilic cationic protein) • Lymphocytes • TH1 : IL-2 & IFN-  growth and differentiation of B cell, • activation of macrophages • TH2 : IL-4 & IL-5  stimulate immunoglobulin secretion, • eosinophil proliferation, differentiation, activation • Neutrophils • Chemotactic factor : LTB4, ECF-A, NCF-A

8. Initial allergen exposure : allergic sensitization Allergen

9. Subsequent allergen exposure : allergic symptoms Allergen Hyperresponsiveness Late response Early response

10. Cell membrane phospholipid Arachidonic acid Leukotriene A4 Leukotriene B4 Prostaglandin G2 Leukotriene C4 Prostaglandin H2 Leukotriene D4 Thromboxane A2 Prostacycline Leukotriene E4 Prostaglandin D2,E,F2

11. Etiology 1. Allergens : dependent on IgE response House dust mite(most common) Pollen(tree, grass, weed) 2. Pharmacologic stimuli aspirin, tartrazine beta-adrenergic antagonists sulfiting agents 3. Environment and air pollution ozone, nitrogen dioxide, sulfur dioxide 4. Occupational factors toluene diisocyanate(TDI), nickel 5. Infections : most common stimuli of acute exacerbation 6. Exercise running, inhalation of cold air !! Swimming is good for asthma 7. Emotional stress

12. Aspirin sensitive asthma • Primarily affects adults • Preferential generation of leukotrienes • Begins with perennial vasomotor rhinitis •  hyperplastic rhinosinusitis with nasal polyps • Cross reactivity between aspirin and other NSAIDs • Indomethacin, fenoprofen, naproxen, zomepirac sodium, • ibuprofen, mefenamic acid, phenylbutazone • !! Well tolerated drugs • acetaminophen, sodium salicylate, choine salicylate, • salicylamide, propoxyphene • Desensitized by daily administration of the drug •  Cross tolerance also develops to other NSAIDs

13. Pathology • Hypertrophy of the bronchial smooth muscle • Hyperplasia of mucosal and submocosal vessels • Mucosal edema • Denudation of the surface epithelium • Pronounced thickening of the basement membrane • Eosinophilic infiltrates in the bronchial wall

14. Normal Lungs Asthmatic Lungs Normal alveoli Collapsed alveoli Hyperinflated alveoli

15. Pathophysiology (1) Contraction of smooth muscle,Vascular congestion Edema of the bronchial wall Reduction of airway diameter Increase in airway resistance Decrease in forced expiratory volumes and flow rates Alterations in respiratory muscle function Changes in elastic recoil Abnormal distrubution of both ventilation and pulmonary blood flow with mismatched ratios Altered arterial blood gas concentrations

16. Elastic recoil of lung Expiratory muscles Ordinary and accessory inspiratory muscles Asthmatic expiration with airway closure

17. Pathophysiology (2) RVH, pulmonary hypertension FVC ≤ 50% of normal FEV1 ≤ 30% of predicted Maximum/minimum midexpiratory flow rates ≤ 20% Residual volume(RV) ≈ 400% of normal Hypoxia is a universal finding but frank ventilatory failure is relatively uncommon(10-15%) Hypocapnia and respiratory alkalosis Normal PaCO2 tends to be associated with quite severe levels of obstruction(impending respiratory failure)

18. Normal Acute asthma

19. Pathophysiology (2) RVH, pulmonary hypertension FVC ≤ 50% of normal FEV1 ≤ 30% of predicted Maximum/minimum midexpiratory flow rates ≤ 20% Residual volume(RV) ≈ 400% of normal Hypoxia is a universal finding but frank ventilatory failure is relatively uncommon(10-15%) Hypocapnia and respiratory alkalosis Normal PaCO2 tends to be associated with quite severe levels of obstruction(impending respiratory failure)

20. Normal ventilation and perfusion Ventilation/perfusion mismatch in asthma

21. Clinical Features Triad : dyspnea, cough, wheezing Nocturnal awakening with dyspnea and/or wheezing Prolonged expiration Tachypnea, tachycardia, mild systolic hypertension Overinflated lungs Use of accessory muscles , Paradoxical pulse Extremely valuable in indicating the severity of the obstruction Cough/sputum Curschmann’s spirals, eosinophils, Charcot-Leyden crystals Atelectasis Spontaneous pneumothorax/pneumomediastinum

22. Clincal signs and severity of asthma Confusion, loss of consciousness D E A T H Cyanosis Pulsus paradoxus Use of accessory muscles Speech Sentences Words None Breathless at rest Audible wheeziness Stethosco-pic rhonchi Mild asthma Moderate Severe Very severe

23. Pulsus paradoxus

24. Differential Diagnosis 1. Upper airway obstruction by tumor or laryngeal edema stridor, harsh respiratory sounds localized to tracheal area absent of diffuse wheezing throughout both lung fields indirect laryngoscopy or bronchoscopy 2. Glottic dysfunction narrow glottis during inspiration and expiration occasional PaCO2 retention but preserved PaO2 3. Endobronchial disease(tumor, bronchial stenosis, foreign body) persistent localized wheezing 4. Acute left ventricular failure 5. Chronic bronchitis no true symptom-free periods, chronic cough,sputum 6. Recurrent pulmonary emboli lung scan, pulmonary angiography 7. Carcinoid tumor 8. Eosinophilic pneumonias 9. Systemic vasculitis

25. Diagnosis History : personal or family history of allergic diseases (eczema, rhinitis, urticaria), occupation, contact with animals Reversible airway obstruction ≥ 15% in FEV1 following beta-adrenergic agonist Provocation test (methacholine, histamine, cold air) ≥ 20% in FEV1 Skin tests Sputum and blood eosinophilia Serum IgE levels Chest X-ray : hyperinflation

26. Questions to an asthma patient • Do any of your patents, siblings or children have childhood eczema, asthma or hay fever? • Have you ever had eczema or hay fever? • Do you smoke/have you smoked? • What is your occupation? • Are you in contact with animals? • Can you tolerate acetylsalicylic acid? • How old were you when the disease strarted? • Did the disease first strart with :episodes of wheezing(asthma) daily productive cough(bronchitis), breathlessness on effort(emphysema)? • Is there any difference between asthma : indoors/outdoors, at home/at place of work, in spring/summer/autumn/winter? • What factors start or worsen your asthma? • Are you ever completely free from chest symptoms? • Have you ever been treated with steroid tablets for asthma? • How often do you use your bronchodilator spray? • How many days/times per month: do you have asthma symptoms? Do you wake with asthma? Do you stay home from school/work?

27. Atopic dermatitis : Eczema

28. Keratoconjunctivits Papillary hypertrophy in upper tarsal conjunctiva

29. Atopic kerato-conjunctivitis Thickened lid margins Eczematous skin

30. Allergic rhinitis

31. Diagnosis History : personal or family history of allergic diseases eczema, rhinitis, urticaria, atopy Reversible airway obstruction ≥ 15% in FEV1 following beta-adrenergic agonist Provocation test (methacholine, histamine, cold air) ≥ 20% in FEV1 Skin tests Sputum and blood eosinophilia Serum IgE levels Chest X-ray : hyperinflation

32. Dyspnea, cough Beta 2 inhaler PEF increases ≥ 15% No No Yes Reduced PEF Normal PEF Diary with PEF for 14days Diary with PEF for 14days The diagnosis is Asthma Yes Yes PEF varies ≥ 20% PEF varies ≥ 20% No No Normal lung function reduced lung function Yes Yes Bronchoprovocation Corticosteroid in 14days PEF increases ≥ 20% PEF falls ≥ 20% Not asthma No No

33. Diagnosis History : personal or family history of allergic diseases eczema, rhinitis, urticaria, atopy Reversible airway obstruction ≥ 15% in FEV1 following beta-adrenergic agonist Provocation test (methacholine, histamine, cold air) ≥ 20% in FEV1 Skin tests Sputum and blood eosinophilia Serum IgE levels Chest X-ray : hyperinflation

34. Treatment • Elimination of the causative agents from the environment of an allergic asthmatics • Desensitization or immunotherapy with extracts of the suspected allergens • Drug treatment • ⑴ Adrenergic stimulants (epinephrine, beta2 agonist) • ⑵ Methylxanthines (theophylline) • ⑶ Anticholinergics (ipratropium bromide) • ⑷ Glucocorticoids • ⑸ Mast cell-stabilizing agents (cromolyn sodium, nedocromil) • ⑹ Leukotriene antagonist

35. Prognosis and clinical course Mortality rate from asthma is small. Good prognosis for 50-80% of all patients, particularly whose disease is mild and develops in childhood. 26-78% still have asthma 7-10 years after initial Diagnosis. 6-19% continue to have severe disease 20% spontaneous remission Asthma is not progressive unlike other airway diseases such as chronic bronchitis. Asthma developing irreversible changes in lung function : comorbid stimuli such as cigarette smoking