1. Restrictive Lung Diseases Dr. Raid Jastania

2. “Don’t forget the homework”

3. Restrictive Lung Diseases • Definition: • Reduced lung compliance • More pressure needed to expand lungs • Lungs are stiff • Pulmonary function test: Low VEV1, Low FVC (the ratio FEV1/FVC is normal)

4. Restrictive Lung Diseases • Types: • Chest wall abnormality (not primary lung) • Deformities, kyphoscoliosis • Neuromuscular disease • Primary lung disease • Acute: Acute Respiratory Distress Syndrome ARDS • Chronic: • Occupational: Asbestosis, silicosis, coal worker pneumoconiosis • Interstitial lung disease (interstitial pneumonia), Idiopathic pulmonary fibrosis • Immune diseases: Sarcoidosis, SLE, RA, Wegener • Physical injury: : Radiation • Drugs: Chemotherapy, methotrexate

5. Restrictive Lung Diseases • Gas exchange barrier: • Basement membrane • Interstitial tissue • Endothelial cell • Epithelial cell

6. Restrictive Lung Diseases • Initial injury to cells: endothelial, epithelial • This is followed by reaction that end by interstitial fibrosis – stiff lung – dyspnea • Damage to epithelium and vessels – abnormal ventilation-perfusion – Hypoxia – cyanosis • Pulmonary hypertension – cor pulmonale

7. Acute Lung Injury – Acute Respiratory Distress Syndrome ARDS

8. Acute Lung Injury – Acute Respiratory Distress Syndrome ARDS • Continuum of the same condition • Characterized by progressive respiratory failure: • Acute onset dyspnea • Decreased arterial oxygen pressure (hypxemia) • Bilateral pulmonary infiltrates (edema) • Absence of evidence of left-sided heart failure • Most common cause of non-cardiogenic pulmonary edema

9. Acute Lung Injury – Acute Respiratory Distress Syndrome ARDS • Can be caused by many conditions: • Direct injury to lung: Pneumonia, aspiration, pulmonary contusion (trauma), fat embolism, near-drowning, inhalation injury, post-lung transplant • Indirect Lung injury: Sepsis, severe trauma with shock, cadiopulmonary bypass, acute pancreatitis, transfusion, uremia

10. Acute Lung Injury – Acute Respiratory Distress Syndrome ARDS • Pathogenesis: • Epithelial or endothelial injury • Inflammation: increased vascular permeability, edema, fluid in alveoli, loss of diffusion capacity, loss of surfactant, damage of typeII pneumocytes • Proinflammatory cytokines>> Anti-inflammatory cytokines • Cytokines: • IL-8: Chemotaxis of neutrophils • IL-1, TNF • Neutrophils: • Oxidative damage • Attract other inflmmatory cells: IL-1, TNF • Fibrosis/Repair: TGF-alpha, PDGF

11. Acute Lung Injury – Acute Respiratory Distress Syndrome ARDS • Morphology: • Diffuse alveolar damage • 1. Exudative phase • 2. Proliferative phase • 3. Fibrotic phase

12. Acute Lung Injury – Acute Respiratory Distress Syndrome ARDS • 1. Exudative phase • Lung is dark, red, firm • 0-7 days • Capillary congestion • Necrosis of epithelial cells • Interstitial, alveolar edema, hemorrhage • Collection of neutrophils • Alveolar collapse (loss of surfactant) • Fibrin thrombi • Hyaline membrane lining alveolar ducts

17. Acute Lung Injury – Acute Respiratory Distress Syndrome ARDS • 2. Proliferative phase • 1-3 weeks • Proliferation of type II pneumocytes • Macrophages, removing cell debris • 3. Fibrotic phase • Resolution with minimal fibrosis • Repair/Fibrosis, thick alveolar walls • Progressive fibrosis (honeycomb lung) Rare

18. Acute Lung Injury – Acute Respiratory Distress Syndrome ARDS • Clinical: • Mortality was 100% • Now 30-40% with good ICU support • Poor prognosis: old age, multisystem failure, high levels of IL-1

19. Chronic Restrictive Lung Diseases

20. Chronic Restrictive Lung Diseases • Group of different diseases • Similar clinical, pulmonary function test and pathological findings • Represent 15% of non-infectious diseases of lungs • End-stage: diffuse interstitial pulmonary fibrosis (Honeycomb lung)

21. Restrictive Lung Diseases • Primary lung disease • Acute: Acute Respiratory Distress Syndrome ARDS • Chronic: • Occupational: Asbestosis, silicosis, coal worker pneumoconiosis • Interstitial lung disease (interstitial pneumonia), Idiopathic pulmonary fibrosis • Immune diseases: Sarcoidosis, SLE, RA, Wegener • Physical injury: : Radiation • Drugs: Chemotherapy, methotrexate

22. Idiopathic Pulmonary Fibrosis • Cryptogenic fibrosing alveolitis • Unknown etiology • Diffuse interstitial fibrosis • Sever hypoxemia, and cyanosis • Male>Female, 60y • Diagnosis of exclusion

23. Idiopathic Pulmonary Fibrosis • Pathogenesis: • Alveolar wall injury • Alveolitis: inflammation, edema • Neutrophil, macrophages, lymphocytes • Interstitial Fibrosis • ? Immune disorder: association with immune diseases: RA, SLE, Sjogren…. • Macrophages: IL-8, FGF, TGF-beta, PDGF

24. Idiopathic Pulmonary Fibrosis • Morphology: • Interstitial lung disease • Interstitial pneumonia • Usual interstitial pneumonia • Non-specific interstitial pneumonia • Desquamative interstitial pneumonia • Lymophocytic interstitial pneumonia • Bronchiolitis Obliterance Organizing Pneumonia BOOP

25. Idiopathic Pulmonary Fibrosis • Morphology: • Usual interstitial Pneumonia UIP • Random pattern of interstitial chronic inflammation, fibrosis, in variable stages • 80% idiopathic, 20% associated with collagen vascular diseases

32. Idiopathic Pulmonary Fibrosis • Clinical: • Gradual, non-productive cough • Progressive Dyspnea, cyanosis • Finger clubbing • Mean survival 2-4 years

33. Sarcoidosis • Multisystem disease • Unknown etiology • Non-caseating granuloma in many tissues and organs • Diagnosis of exclusion

34. Sarcoidosis • Presenting Picture: • Bilateral hilar lymphadenopathy • Lung involvement, lung nodules • Other organs: skin, eye, any tissue • Adult, younger than <40y • Common in US blacks • Higher in non-smokers

35. Sarcoidosis • Pathogenesis • Unknown cause • Immunologic factors • Activated CD4 T cells • Increase number of CD4 Tcells • High level f IL-2, Interferon-gamma, IL-8, TNF • Genetic factors: • Familial, racial clustering • Association with HLA-A1, HLA-B8 • Environmental factors • ? Viral infection, mycobacteria

36. Sarcoidosis • Morphology: • Non-caseating granuloma • Collection of epithelioid histiocytes rimmed by CD4 T-cells and fibroblasts • Giant cells • Schqumann bodies (calcium and protein_ • Asteroid bodies (inclusions)

38. Sarcoidosis • Hilar and paratracheal lymph nodes 75-90% • Lung involvement in 90% • Diffuse interstitial fibrosis 5-15% • Sking 25% • Erythema nodosum: raised, tender, nodule on anterior aspect of legs • Eye, Lacrimal glands • Iritis, loss of vision • Choroiditis, retinitis • Parotid gland 10%, Spleen 75%, Liver, Bone marrow, any organ

39. Sarcoidosis • Clinical: • Asymptomatic in many • Lymphadenopathy, skin, eye lesion • Respiratory disease: dyspnea, dry cough • Fever, fatigue, wt. Loss • Unpredictable course • Progressive or relapsing remitting disease • 10% develop progressive fibrosis

40. Hypersensitivity Pneumonitis • Immune mediated disease • Type III and type IV hypersensitivity • Inflammatory disease • Affect alveoli (mainly) (Allergic Alveolitis) • Occupational disease • Restrictive disease

41. Hypersensitivity Pneumonitis • Presentation: • Acute: 4-6 hours following exposure, Fever, cough , dyspnea • Chronic: cough, dyspnea, wt. Loss

42. Hypersensitivity Pneumonitis • Causes • Fungal/Bacterial • Farmer lung: micropolyspora • Humidifier lung: Actinomycetes • Cheese washer’s lung: Penicillium • Animal Product • Pigeon breeder’s lung • Chemicals

43. Hypersensitivity Pneumonitis • Morphology: • Particles: not usually seen • Inflammation, edema, Peribronchial • Lymphocytes, plasma cells • Non-caseating granuloma • Fibrosis

44. Collagen Vascular Disease • Associated with interstitial Pneumonia • Similar to Idiopathic Pulmonary Fibrosis

45. Wegener Granulomatosis • Necrotizing vasculitis • Affect both upper and lower respiratory tract • Parenchymal necrotizing granuloma • URT: sinusitis, epistaxis, nasal perforation • LRT: cough, hemoptysis, chest pain