Restrictive Lung Diseases Dr. Raid Jastania

“Don’t forget the homework”

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)

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

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

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

Acute Lung Injury – Acute Respiratory Distress Syndrome ARDS

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

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

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

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

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

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

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

Chronic Restrictive Lung Diseases

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)

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

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

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

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

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

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

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

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

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

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)

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

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

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

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

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

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

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

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