Interstitial Lung Diseases PDF

Restrictive Lung Diseases (Interstitial Lung Diseases) Professor Mohamad Nidal Khabaz  RESTRICTIVE PULMONARY DISEASES FVC is reduced & expiratory flow rate is normal or reduced. The ratio of FEV1 to FVC is near normal. The restrictive defect occu...

Restrictive Lung Diseases (Interstitial Lung Diseases) Professor Mohamad Nidal Khabaz  RESTRICTIVE PULMONARY DISEASES FVC is reduced & expiratory flow rate is normal or reduced. The ratio of FEV1 to FVC is near normal. The restrictive defect occurs in two general conditions: chest wall disorders in the presence of normal lungs such as severe obesity, or diseases of the pleura, neuromuscular disorders (Guillain-Barré syndrome; affect respiratory muscles) Usual cause is acute or chronic interstitial lung disease (primary or secondary) ARDS (Acute respiratory distress syndrome) Chronic restrictive diseases such as pneumoconioses interstitial fibrosis of unknown etiology, infiltrative conditions (e.g., sarcoidosis)  Diseases which interfere with lung expansion Chest wall defects Pulmonary parenchymal diseases (Interstitial Lung Diseases) Destruction of alveolar walls with FIBROSIS Predominantly diffuse, more in peripheral areas Decreased lung compliance (stiff lung) & Increase in effort to breath → dyspnea Decreased arterial O2 pressure due to abnormalities in ventilation- perfusion ratio leading to hypoxemia (resistant to O2 therapy)  Major types of Interstitial Lung Diseases Fibrosing Idiopathic Pulmonary Fibrosis (IPF) Nonspecific Interstitial Pneumonia Cryptogenic Organizing Pneumonia Associated with Collagen Vascular Diseases Pneumoconiosis Drug Related (Chemotherapy & Anti-arrythmia) & Radiation Induced Granulomatous: Sarcoidosis, Hypersensitivity Pneumonitis Eosinophilic: Pulmonary Eosinophilia (Loeffler syndrome) Smoking – Related: Desquamative interstitial pneumonia, Respiratory bronchiolitis  Pathogenesis Whatever the cause, the lesion is an alveolitis Lymphocytes, macrophages & neutrophils infiltration Macrophage activation→ chemoatractants IL-8 & Leukotrine B4 → Recruit Neutrophils Fibrogenic Cytokines (TGF-β & PDGF) Activation of Fibroblasts Destruction of type I pneumocytes & proliferation of type II pneumocytes  Fibrosing Reaction 1. Idiopathic Pulmonary Fibrosis (IPF) (Cryptogenic Fibrosing Alveolitis) Commonest type, M  F, most  60, (diffuse interstitial fibrosis) Diagnosed only after exclusion of all other causes Gross: Cobblestone outer surface of lung Microscopy: Histological pattern of Usual Interstitial Pneumonia (UIP) Patchy interstitial fibrosis (varying in intensity & time) Temporal Heterogeneity i.e. Fibroblastic foci + Collagenous foci The dense fibrosis causes collapse of alveolar walls and formation of cystic spaces lined by hyperplastic type II pneumocytes or bronchiolar epithelium (honeycomb fibrosis). Interstitial inflammation: patchy consists of an alveolar septal infiltrate (mostly lymphocytes and occasional plasma cells, mast cells, and eosinophils) Lower lobe predominance, along pleura & septa  Idiopathic Pulmonary Fibrosis Interstitial fibrosis in Honeycomb lung Honeycomb Lung  Insidious presentation: Nonproductive cough & progressive dyspnea  Examination: Cyanosis, clubbing, bibasal rales, X ray (bibasal nodular infiltrates)  Pulmonary function tests (restrictive)  Lung biopsy  Prognosis : Death in 2-4 years  Fibrosing Reaction 2. Nonspecific Interstitial Pneumonia Similar to previous, but more diffuse & without heterogeneity & no fibroblasts Cellular inflammatory & Fibrosing patterns 3. Pulmonary involvement in Collagen Vascular Diseases : Systemic Lupus Erythematosus ( SLE ), Rheumatoid Arthritis & Others 4. Cryptogenic Organizing Pneumonia (Bronchiolitis Obliterans Organizing Pneumonia (BOOP)) Many causes (inflammatory, vascular) but mainly cryptogenic Polypoid plugs of fibrosis in bronchioles & alveolar ducts & alveoli No destruction of lung architecture Recovery within 6 months with steroids  Fibrosing Reaction 5- Pneumoconiosis: Environmental / occupational diseases Nature of inhaled product determines extent of disease Factors that determine the damage include: Size, shape, solubility and reactivity of particles Particles 5-10 trapped in URT 1 - 5  reach alveolar walls ≤ 0.5  penetrate alveolar epithelium Chemical composition (silica & asbestos are reactive than coal dust) Concentration & duration of exposure Co - existence of other diseases Individual susceptibility  Pneumoconiosis A- Coal Workers' Pneumoconiosis (CWP) Anthracosis (Coal miner’s lung) Inhalation of carbon & deposition in bronchioles, LN & alveolar septae (more in upper lobes) Asymptomatic anthracosis Simple Coal Workers' Pneumoconiosis Centrilobular emphysema with carbon laden macrophages coal macules and the somewhat larger coal nodule Progressive Massive Fibrosis (carbon + silica): Emphysema + large solid areas of progressive fibrosis (Anthrasilicosis) increasing pulmonary dysfunction, pulmonary hypertension, and cor pulmonale No risk of lung cancer Anthracosis with Fibrosis  Pneumoconiosis B- Silicosis Commonest occupational lung disease in the world inhalation of crystalline silica Workers in sandblasting, ceramics, glass, and stone cutting, construction….etc Acute heavy exposure ARDS Chronic after 20-40 yrs exposure Pathogenesis: Silica in macrophages cause activation and release of mediators by pulmonary macrophages (IL-1, TNF, fibronectin, lipid mediators, oxygen-derived free radicals and fibrogenic cytokines)  Pneumoconiosis B- Silicosis Pathology Silicotic nodules, in upper lobe & LNs Small nodules large nodules (1-10cm) of concentrically arranged collagen fibers with polarizing crystalls in the center Cavitation, pleural fibrosis. Fibrotic calcified nodules in hilar lymph nodes → X ray : Eggshell calcification Progressive Massive Fibrosis & Honeycomb Clinical picture Many patients are asymptomatic, some with shortening of breath Progressive Massive Fibrosis (PMF) late with abnormal pulmonary function, pulmonary hypertension & cor pulmonale Patients more susceptible to T.B.  risk lung cancer with crystalline silica Silicotic Nodule  Pneumoconiosis C-Asbestos induced lesions Workers in installation & insulation materials OR those in close contact Long latency (10-20 yrs.), dyspnea, cough associated with production of sputum. May progress to CHF, cor pulmonale, and death Asbestosis is marked by diffuse pulmonary interstitial fibrosis. Asbestos Bodies (Ferruginous Bodies) golden brown, fusiform or beaded rods with a translucent center Found in sputum & bronchial wash & lung tissue composed of: Asbestos fibers + protein + iron ( positive Perl’s stain) Lesions include: Asbestosis : chronic diffuse interstital fibrosis lower lobe Honeycomb lung & cor pulmonale Pleural effusion, Pleural fibrosis, Pleural plaques Malignant Mesothelioma  risk lung, larynx, stomach & colon carcinomas Asbestos body in macrophage Pleural Plaques  Granulomatous Reaction 1- Sarcoidosis (Multisystem disorder )  in US blacks, and Scandinavians, Nonsmokers, Adults younger than 40 y Etiology: remains unknown May be asymptomatic or insidious onset of fever, malaise, cough & dyspnea; Majority recover ( ± steroid therapy ) 20% have respiratory dysfunction Some patients may have additional obstructive symptoms Pathology Lesions are noncaseating granulomas with giant cells containing Schaumann & Asteroid bodies Lymph nodes 75-90% hilar, 30% peripheral Lung : 90% Interstitium, parabronchioles, paravenules and pleura. 5-15% progress to interstitial fibrosis (honeycomb lung) Spleen, liver, BM, skin, eyes, lacrimal & salivary glands Sarcoid Granuloma Asteroid body Schaumann body  Granulomatous Reaction 2. Hypersensitivity Pneumonitis (Allergic Alveolitis) Syndrome caused by a variety of inhaled organic dust or chemicals Inflammatory response is in alveoli & terminal bronchiols with systemic symptoms Type III & type IV reactions with specific AB in serum Presentation depends on duration & intensity of exposure: Acute or Chronic Antigens include fungal or bacterial spores, animal protein --- etc Farmer’s Lung - moldy hay with fungal spores Pigeon fancier’s lung - Bird droppings Coffee worker’s lung - Coffee been dust Sugar cane workers Ventilation related Many others  Phases of Hypersensitivity Pneumonitis : Acute: direct irritant effect cough with dyspnea, fever (4-8hr. after Extrinsic allergic alveolitis with exposure) granuloma Chronic: insidious onset cough, dyspnea, weight. Morphology: Patchy peribronchiolar interstitial inflammatory infiltrate & alveolar walls 75% show interstitial noncaseating granuloma FIBROSIS Smoking –Related Interstitial Diseases Desquamative Interstitial Pneumonia (DIP) Interstitial inflammation + pigmented macrophages in alveolar spaces Respond to steroids Bronchiolocentric respiratory bronchiolitis with peribronchial fibrosis  Desquamative interstitial pneumonia: medium-power detail of lung to demonstrate the accumulation of large numbers of mononuclear cells within the alveolar spaces with only mild fibrous thickening of the alveolar walls.