1. Chronic Obstructive Airways Disease Gerard Flaherty B.Sc.(Hons.), M.B., B.Ch., B.A.O., M.R.C.P.I. Specialist Registrar in General Medicine/Endocrinology

2. Lecture Outline Definition of COAD Diagnostic criteria Classification of severity Epidemiology Chronic bronchitis Emphysema Bronchiectasis Bronchial asthma

3. Definition of COAD COAD is a disease state characterised by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases.

4. Epidemiology of COAD Prevalence and morbidity data greatly underestimate the total burden of COAD. Prevalence of 9.34/1,000 in men and 7.33/1,000 in women (Global Burden of Disease Study, 1990). Morbidity increases with age and is greater in men than in women. Currently the 4 th leading cause of death in the world. Economic burden: per capita cost of COAD in UK of US$65 (1996).

5. Risk Factors for COAD Host factors Alpha-1-antitrypsin deficiency Asthma and airway hyperresponsiveness Disordered lung development Environmental factors Tobacco smoke Occupational dusts/chemicals Air pollution Childhood infections Lower socioeconomic status

6. Diagnosis of COAD Considered in patients with cough, sputum production, or dyspnoea +/- risk factors. Confirmed by spirometry. FEV 1 /FVC <70% + postbronchodilator FEV 1 <80% of predicted value. A low peak expiratory flow has poor specificity for the diagnosis of COAD.

7. Spirometry Normal flow-volume loop Flow-volume loop in severe COAD

8. Classification of Severity StageCharacteristics 0: At Risk Normal spirometry Cough, Sputum I: Mild COAD FEV 1 /FVC <70% FEV 1 ≥ 80% II: Moderate COAD FEV 1 /FVC <70% FEV 1 50-80% III: Severe COAD FEV 1 /FVC <70% FEV 1 30-50% IV: Very Severe COAD FEV 1 /FVC <70% FEV 1 <30%

9. Respiratory Failure Results when gas exchange is inadequate, resulting in hypoxia with PaO 2 <8kPa. Type I: Hypoxia with normal/low PaCO 2. Caused by ventilation/perfusion mismatch, e.g., Life- threatening asthma, Emphysema. Type II: Hypoxia with hypercapnia (PaCO 2 >6.5kPa). Caused by alveolar hypoventilation, e.g., Chronic bronchitis. Oxygen therapy must be controlled in type II respiratory failure due to the risk of further hypercapnia if the hypoxic drive to ventilation is abrogated by excessive oxygen.

11. Chronic Bronchitis Persistent cough with sputum production for at least 3 months in ≥ consecutive years Simple / Chronic asthmatic / Obstructive Most frequent in middle-aged men Higher incidence in urban dwellers May coexist with emphysema Presents with exertional dyspnoea and frequent respiratory tract infections

12. Chronic Bronchitis Pathogenesis Chronic irritation by inhaled substances Respiratory infections 4-10 times more common in heavy smokers Hypersecretion of mucus in large airways Submucosal gland hypertrophy Increase in goblet cells in small airways Excessive mucus → airway obstruction Cigarette smoke predisposes to infection

13. Chronic Bronchitis Morphology Gross Hyperaemia and oedema of mucous membranes Excessive secretions +/- casts Histology Hypertrophy of submucosal smooth muscle Hyperplasia of submucosal glands of trachea/bronchi Increased Reid index (>0.4) Squamous metaplasia and dysplasia of epithelium Loss of ciliary activity Narrowing of bronchioles +/- bronchiolitis obliterans

14. Chronic Bronchitis Histology

15. Chronic Bronchitis Complications ↓PaO 2 ↑PaCO 2 ….Respiratory failure Respiratory tract infections (H. influenzae, Strep. Pneumoniae) Pulmonary hypertension → Cor pulmonale Atypical metaplasia / dysplasia of respiratory epithelium….Bronchogenic carcinoma

17. Emphysema Abnormal permanent enlargement of the airspaces distal to the terminal bronchiole, accompanied by destruction of their walls Types: (1) centrilobular (2) panlobular (3) paraseptal (4) irregular Associated with heavy cigarette smoking

18. Emphysema Presents with progressive dyspnoea, reduced exercise tolerance, wheeze and weight loss Signs of hyperinflation Loss of elastic support → Airways collapse on expiration → Obstructive pattern on spirometry Respiratory acidosis Cor pulmonale (rarely) Pneumothorax

19. Emphysema

20. Emphysema Pathogenesis Protease-antiprotease hypothesis Homozygous alpha-1-antitrypsin deficiency is associated with panlobular emphysema, especially in smokers Emphysema results from the destructive effect of high protease (elastase) activity in patients with low antiprotease activity Smoking stimulates release of elastase from neutrophils

21. Emphysema Pathogenesis

22. Emphysema Morphology Gross Panlobular: resp. bronchiole → terminal alveoli. Lower > Upper lobes Centrilobular → respiratory bronchioles. Upper > Lower Paraseptal → distal acinus. Upper > Lower Irregular → associated with scarring, e.g., Tuberculosis Histology Destruction of septal walls Fusion of adjacent alveoli Blebs / bullae Compressed blood vessels +/- Bronchitis

23. Emphysema Subtypes

24. Emphysema Gross

25. Emphysema Histology

27. Bronchiectasis A chronic necrotising infection of the bronchi and bronchioles associated with abnormal permanent dilation of these airways Presents with cough, productive of large amounts of foul-smelling, purulent sputum, hamoptysis and digital clubbing Pooled secretions in lower lobes → respiratory tract infections

28. Bronchiectasis Aetiology Bronchial obstruction Tumour, foreign bodies, mucous impaction Asthma / Chronic bronchitis Infection Tuberculosis, Staphylococcus aureus, ABPA, Measles, Pertussis Congenital Congenital bronchiectasis, Cystic fibrosis, Intralobar sequestration, Immunodeficiency, Kartagener’s syndrome, Yellow nail syndrome

29. Cystic Fibrosis Genetic defect

30. Bronchiectasis Pathogenesis Bronchial obstruction → Atelectasis Dilatation of walls of patent airways Infection → Bronchial wall inflammation → weakened walls → further dilation Cystic fibrosis: squamous metaplasia with impaired mucociliary action, infection, necrosis of bronchial and bronchiolar walls Kartagener’s syndrome: absent dynein arms in cilia → lack of ciliary activity

31. Bronchiectasis Morphology Gross Usually both lower lobes May be localised Dilated airways Cylindroid Fusiform Saccular Cystic pattern on cut surface of lungs Histology Acute and chronic inflammation Desquamation of epithelium Necrotising ulceration Squamous metaplasia Necrosis → lung abscess Fibrosis

32. Bronchiectasis Computed Tomography

33. Bronchiectasis Gross

34. Bronchiectasis Histology

35. Bronchiectasis Complications Pneumonia Lung abscess Empyema Septicaemia Cor pulmonale Metastatic cerebral abscesses Secondary Amyloidosis

37. Bronchial Asthma Hyper-reactive bronchioles, leading to episodic, reversible bronchoconstriction Bronchospasm → cough, dyspnoea, wheeze Status asthmaticus may be fatal Types: (1) Extrinsic (eg, atopic, occupational, ABPA*) – type 1 reaction (2) Intrinsic (eg, respiratory infections, aspirin, exercise)

38. Bronchial Asthma Pathogenesis Atopic Asthma Exposure of presensitised IgE- coated mast cells to antigen causes acute immediate response Chemical mediators (histamine, cytokines, PAF, leukotrienes) Late-phase reaction Nonatopic Asthma Virus-induced inflammation of respiratory mucosa lowers threshold of vagal receptors to irritants Aspirin-sensitive asthma a/w rhinitis/nasal polyps Occupational asthma

39. Bronchial Asthma

40. Dermatophagoides pteronyssinus (House dust mite)

41. Bronchial Asthma Morphology Gross Overdistended lungs Mucous plugs occlude bronchioles Histology Thickened basement membrane Oedema Inflammatory infiltrate Numerous eosinophils Hyperplasia of submucosal glands Bronchial wall muscle hypertrophy Curschmann’s spirals Charcot-Leyden crystals (eosinophil membrane protein)

42. Bronchial Asthma Histology

43. Bronchial Asthma Complications Status asthmaticus Pneumothorax Bronchiectasis Cor pulmonale