Pulmonary Fibrosis & Bronchiectasis Omer Alamoudi, MD, FRCP, FCCP, FACP

1. Pulmonary Fibrosis &Bronchiectasis Omer Alamoudi, MD, FRCP, FCCP, FACP Professor, consultant Pulmonologist Department of Medicine, KAUH Email: dramoudi@yahoo.com

2. Pulmonary fibrosis, Idiopathic (IPF) • Definition • Causes • Clinical presentation • pathology • Diagnosis • Management

3. Chronic progressive disease of unknown etiology Characterized by inflammation and fibrosis of the lung parenchyma Lung interstitium and alveoli Idiopathic Pulmonary fibrosis (IPF)Definition

4. Pulmonary fibrosis, Idiopathic (IPF) • Definition • Causes • Clinical presentation • Pathology • Diagnosis • Management

5. Unknown (90%) Familial (AD) Viral (Epstein Barr virus) Collagen vascular disorder (RA, scleroderma, SLE, dermatomyositis) Asbestosis Drugs (Amiodarone, Busulphan, Bleomycin) PCP Radiation pneumonitis Recurrent Intraalveolar hemorrhages Chronic aspiration pneumonia Smoking, wood, metal dust exposure Granulomatosis (Sarcoidosis, histoplasmosis) IPFCauses

6. Pulmonary fibrosis, Idiopathic (IPF) • Definition • Causes • Clinical presentation • pathology • Diagnosis • Management

7. Pulmonary fibrosis, Idiopathic (IPF)Clinical presentation • Onset: Usually between 50 and 70 yr • Clinical presentation • Progressive dyspnea on exertion • Paroxysmal cough, usually nonproductive • Clubbing of the fingers (50%) • Fine inspiratory basal crackles chest auscultation • Abnormal chest x-ray or HRCT • Restrictive pulmonary physiology with reduced lung volumes and DLCO and widened AaPO2

8. Pulmonary fibrosis, Idiopathic (IPF)Clinical presentation • Signs of pulmonary hypertension • Loud P 2 • Right ventricular heave • RBBB • Signs of Corpulmonale and Rt heart failure • Raised JVP • Hepatomegaly, ascitis • Lower limb edema • Signs of underlying causes (RA, scleroderma)

9. Pulmonary fibrosis, Idiopathic (IPF) • Definition • Classification • pathogenesis • Causes • Clinical presentation • Pathology • Diagnosis • Management

10. IPF: Pathology • UIP is essential to diagnosis of IPF • Idiopathic, progressive, diffuse fibrosing inflammatory process • Involves lung parenchyma • Surgical lung biopsy • suspected IPF • Atypical clinical or radiographic features • Major purpose of histologic examination is to distinguish UIP from other histologic subsets of IIP

11. HISTOPATHOLOGIC ELEMENTS OF UIP

12. CHRONIC INTERSTITIAL INFLAMMATION IN UIP

13. Pulmonary fibrosis, Idiopathic (IPF) • Definition • Causes • Clinical presentation • Pathology • Diagnosis • Management

14. IPFDiagnosis • Major criteria • Exclusion of other known causes of ILD • Restrictive pulmonary function studies • Bibasilar reticular abnormalities on HRCT scan • No histologic or cytologic features on transbronchial lung biopsy or BAL analysis supporting another diagnosis • Minor criteria • Age >50 yr • Insidious onset of otherwise unexplained exertional dyspnea • Duration of illness 3 mo • Bibasilar, dry (“Velcro”) inspiratory crackles

15. Chest radiograph Early: ground glass appearance Late: reticular, reticulonodular, honeycombing at the periphery Deviation of trachea to the right Diagnosis IPF Bilateral lower lobe opacities and possible mild decrease in lung volumes.

17. Chest radiograph Reduction of the lung volume Pleural involvement, adenopathy, localized parenchymal densities (very rare) Diagnosis IPF

18. Diagnosis IPFHigh Resolution CT (HRCT) • HRCT • Useful to differentiate IPF from other ILD • Determine the severity and extent of the disease • Select the place for biopsy • Findings • Patchy, ground glass attenuation, thickened interlobular septae • Traction bronchiectasis • Reticular pattern, honeycombing

19. Diagnosis IPFHRCT • Distortion of the pulmonary architecture • Thickening of pulmonary interstitium • Ground-glass attenuation. • No obvious honeycombing is present

20. Diagnosis IPFHRCT • Advanced stage of pulmonary fibrosis • Reticular opacities • Honeycombing, predominantly subpleural distribution.

21. HRCT FINDINGS IN IPF

22. Restrictive pattern ↓ FVC ↓ FEV1 ↑FEV1/FVC Diagnosis IPFPulmonary function tests

23. Diagnosis IPFPulmonary function tests • Restrictive pattern • Lung volumes ( TLC, RV, FRC ↓), DLCO ↓

24. Diagnosis IPF • ABG • PO2 Reduced (V/Q mismatch) • PCO2 Normal or Reduced Increased (End stage)

25. Diagnosis IPF • Bronchoscopy & Bronchoalveolar lavage (BAL) • Assess progression of disease • Assess response to therapy • Assess prognosis of disease • Lymphocyte Good prognosis/ respond to therapy • Eosinophil & • neutrophils Poor prognosis/ no response to steroid

26. Diagnosis IPF • Other tests • Lung biopsy (open vs TBBB) most important • Gallium-67 increased (not useful) • PET (position emission tomography) • Glucose uptake increased • ESR, ANA, RF

27. Pulmonary fibrosis, Idiopathic (IPF) • Definition • Causes • Clinical presentation • Pathology • Diagnosis • Management

28. Corticosteroids Other immunosuppressives Azathioprine Cyclophosphamide Antifibrotic agents Colchicine D-Penicillamine IFN- IFN- Pirfenidone Antioxidant agents Glutathione N-acetylcysteine Others Agents that block neutrophil adhesion molecules Inhibitors of specific fibrogenic cytokines and growth factors THERAPEUTIC APPROACHES TO IPF

29. IPFManagement • Should started as early as possible • Duration of therapy 3-6 months • Corticosteroids • Prednisone tablets • Dose 1-1.5mg/kg (30Mg) • Methyl prednisone (pulse therapy 3-5 days) • Dose 1 gm/day

30. IPFManagement • How to assess the response to therapy • Reduction of symptoms • Improvement of lung function tests • Improvement of DLCO • Improvement of chest x ray (alveolitis)

31. IPFManagement • Cyclophosphamide • Dose 2 mg/kg/day (max 200 mg/day) • Leucopenia (WBC < 3000) • Opportunistic infection • Ca bladder • Hemorrhagic cystitis

32. IPFManagement • Azathioprine • 1-2mg/kg/day (max 200Mg/day) • GIT symptoms • Bone marrow suppression • Increase liver enzymes • Leucopenia, and thrombocytopenia (WBC< 3000) • Colchicine (anti-inflammatory) • Dose 0.5mg BID

33. IPFManagement • Oxygen supply (rest and exercise) if PO2< 55 mmHg • Lung transplantation • Age <60 • Progressive disease • Lack of response to therapy • Psychosocial support • Influenza vaccine

34. CAUSE OF DEATH IPF [N=543] 1-7 year FU 60% Died [N=326] Lung cancer 10% Pulmonary embolism 3% Pulmonary infection 3% Cardiovascular disease 27% Other 18% Respiratory failure 39%

35. RISK FACTORS FOR PROGRESSIVE DISEASE Age: >50 yr Gender: male Dyspnea: moderate to severe with exertion History of cigarette smoking Lung function: moderate to severe loss (especially gas exchange with exercise) BAL fluid: neutrophilia or eosinophilia at presentation HRCT scan: reticular opacities or honeycomb changes Response to corticosteroids: poor Pathology: more fibrosis, fibroblastic foci

36. Bronchiectasis

37. Bronchiectasis • Definition • Etiology • Clinical findings • Diagnosis • Management

38. Definition Acquired disorder affecting the major bronchi and bronchioles Permanent dilatation and destruction of bronchial wall Bronchiectasis

39. Bronchiectasis • Definition • Etiology • Pathophysiology • Clinical findings • Diagnosis • Management

40. Bronchiectasis • Factors trigger bronchiectasis • Infection • Impairment of drainage • Airway obstruction • Defect of host defense

41. Causes of Bronchiectasis • Etiology • Pulmonary infections • Tuberculosis • Viral, Mycoplasma Pneumonia • Pertussis (whooping cough) • Mycobacterium Aviumintracellulare (MAI)

42. Causes of Bronchiectasis • Airway obstruction • FB aspiration • Rt lung, lower lobes • Obstructive pneumonia, focal bronchiectasis • LN enlargement • Rt middle lobe syndrome

43. Causes of Bronchiectasis • Defective host defenses • Local • Ciliary Dyskinesia • Systemic • Hypogammaglobulinemia • AIDS

44. Causes of Bronchiectasis • Rheumatic diseases • Rheumatoid arthritis • Sjogren’s syndrome • Inflammatory bowel diseases • Ulcerative colitis • Crohns disease

45. Causes of Bronchiectasis • Kartagener’s syndrome • Immotile cilia • (Dextrocardia, Sinusitis, Bronchiectasis) • Young’s Syndrome • (Sinusitis, Obstructive azoospermia, Bronchiectasis) • Cystic fibrosis

46. Causes of Bronchiectasis • Allergic bronchopulmonary aspergillosis (ABPA) • Central bronchiectasis • High IgE level • Precipitating, specific antibodies to Aspergillus • Long standing asthma • Cigarette smoking • Idiopathic (50%)

47. Bronchiectasis • Definition • Etiology • Clinical findings • Diagnosis • Management

48. Bronchiectasis • Clinical findings • Symptoms • Cough • Daily sputum production • Dyspnea • Hemoptysis • Recurrent pleurisy

49. Bronchiectasis • Clinical findings • Signs • Coarse crackles • Finger Clubbing (50%) • Rhonchi

50. Bronchiectasis • Definition • Etiology • Clinical findings • Diagnosis • Management