Interstitial Lung Disease Updated PDF

INTERSTITIAL LUNG DISEASE Dr Ian Said Huntingford MD, CHAT, CHCCT, FRCPath, CCT (UK)  Interstitial Lung Disease ▪ a heterogenous group of diseases… ▪ some quite common, some very rare ▪ ~15% of respiratory clinical practice ▪ diffuse pare...

INTERSTITIAL LUNG DISEASE Dr Ian Said Huntingford MD, CHAT, CHCCT, FRCPath, CCT (UK)  Interstitial Lung Disease ▪ a heterogenous group of diseases… ▪ some quite common, some very rare ▪ ~15% of respiratory clinical practice ▪ diffuse parenchymal lung injury/ inflammation progressing to fibrosis ▪ diseases spare the airways  Interstitial Lung Disease ▪ often used synonymously with pulmonary fibrosis ▪ strictly this term should be used when there is histological evidence of fibrosis ▪ most diffuse lung disease cause fibrosis to varying degrees  Interstitial Common features Lung Disease ▪ Clinical: dry cough and breathlessness ▪ Lung function: restrictive pattern ▪ Radiology: reticulo-nodular shadowing ▪ CXR ▪ High-resolution CT-scan of thorax  Interstitial Lung Disease Lung function: restrictive pattern restriction of air flow due to reduced expansion of the lung parenchyma 🡻 total lung capacity, vital capacity, residual volume, lung compliance FVC 🡻 FEV1 N or small 🡻 FEV1 : FVC N or high 🡻 carbon monoxide, CO transfer  Open lung biopsy Peripheral fibrosis in idiopathic pulmonary fibrosis  Interstitial Lung Disease CXR Interstitial Lung Disease bilateral basilar reticular abnormalities with ground-glass appearance on high-resolution CT scans of thorax Aetiology Interstitial Lung Disease ▪ many causes with varying treatment ▪ diagnosis has to be actively sought (lung biopsy), as treatment depends on the cause ▪ treatment for one disease (eg steroids for sarcoidosis) may be disastrous for another (eg severe infection) ▪ more than 150 causative entities ▪ 75% unknown aetiology ▪ idiopathic pulmonary fibrosis ▪ 25% aetiology known ▪ may follow occupational exposure  Interstitial Lung Disease Two unresolved problems ▪What is the nature of the initiating agent? ▪What controls inflammation and fibrosis once they start?  Pathogenesis ▪ forsome years it was believed that the primary pathology is in septal walls with inflammation in septa (alveolitis) progressive diffuse septal (interstitial) fibrosis ▪ BUT now the focus is on epithelial injury as a primary event leading to fibroblast activation  Pathogenesis ▪ injury to alveolar epithelial cells (smoke, pollutants) ▪ activation of inflammatory cells and epithelial and endothelial cells ▪ release of fibrogenic cytokines and growth factors ▪ TNF-α, IL-4, transforming growth factor-β, TGF-β, growth factor endothelin-1 ▪ proliferation of fibroblasts 🡻 myofibroblasts (produce extracellular matrix) 🡻 fibrosis 13  Classification of Interstitial Lung Disease based on pathogenesis & morphology Exudative Granulomatous collagen laid down in walls granulomas spare the bases of the lungs and affect the upper incorporation of exudates into lobes the walls affects the bases of the lungs 14  Classification of Interstitial Lung Disease based on pathogenesis & morphology Exudative idiopathic pulmonary fibrosis Granulomatous (cryptogenic fibrosing alveolitis) sarcoidosis systemic disease extrinsic allergic alveolitis CTDs (eg. rheum.arthritis, systemic sclerosis) pneumoconioses pneumoconioses silicosis asbestosis 15 Classification based on pathogenesis & morphology - some more common examples Exudative idiopathic pulmonary fibrosis Granulomatous (cryptogenic fibrosing alveolitis) sarcoidosis systemic disease extrinsic allergic alveolitis CTDs-(eg. rheum. arthritis, systemic sclerosis) pneumoconioses silicosis pneumoconioses asbestosis 16  Simplified Classification for info Clinical Diagnosis Acute interstitial pneumonia Pathological Pattern acute onset, preceded by Acute interstitial pneumonia respiratory infections diffuse alveolar damage poor prognosis ARDS picture Idiopathic pulmonary fibrosis (Cryptogenic fibrosing alveolitis - Usual interstitial pneumonia UIP UK) myxoid fibrosis idiopathic septal inflammation variable males, late 60s 20/100,000 Desquamative interstitial pneumonia Desquamative interstitial DIP pneumonia DIP little fibrosis males, middle aged alveolar macrophages less severe than UIP smokers, asbestos Non specific interstitial pneumonia Non specific interstitial less severe fibrosis, even distribution 17 pneumonia interstitial mononuclear cells no male preponderance  Interstitial Lung Disease Presentation ▪ Symptoms: typically dyspnoea on exertion fatigue cough ▪ Signs: clubbing often bilateral end-expiratory crackles (Velcro crepitations) signs of R heart failure 18  Interstitial Lung Disease Other features ▪ fatigue (may occur even without dyspnoea) ▪ cough (may be only symptom) ▪ non-specific systemic symptoms: e.g. fever and weight loss ▪ incidental abnormalities of lung function tests ▪ an abnormal X-ray in absence of symptoms 19  Interstitial Lung Disease Criteria for diagnosis ▪ abnormal lung function tests with evidence of restriction (reduced vital capacity) and impaired gas exchange) ▪ basilar reticular abnormalities with ground- glass appearance on high-resolution CT scans ▪ lung biopsy or bronchoalveolar lavage (BAL) showing no features to support an alternative diagnosis 20  Interstitial Lung Disease ▪ Open lung biopsy or ▪ VATS –video assisted thoracoscopic surgery 21  Interstitial Lung Disease Common Conditions Idiopathic Pulmonary Fibrosis Extrinsic Allergic Alveolitis Asbestos Related Disease 22  Idiopathic Pulmonary Fibrosis (clinical) (Cryptogenic Fibrosing Alveolitis) Usual Interstitial Pneumonia (pathologists) ▪ onset insidious with dyspnoea and tachycardia ▪ most commonly in fourth and fifth decade ▪ no known aetiology: pathogenesis uncertain ▪ some genetic abnormalities ▪ variant of promoter for gene that codes for mucin, MUC5B ▪ mutations in serum surfactant protein C damages type II alveolar epithelial cells ▪ mutant telomerase (TGF-β reduces activity of 23 telomerase) Idiopathic Pulmonary Fibrosis BASES 24 Idiopathic Pulmonary Fibrosis 25  Honeycomb Lung A B C 26  Pathogenesis ▪ trigger for damage to Type I pneumocyte and alveolar capillary endothelium ▪ repetitive and prolonged damage ▪ acute phase: interstitial oedema/protein exudation into alveoli (fibrin: early membranes – ARDS picture) ▪ interstitial inflammation (mainly lymphocytes) and Type II Pneumocyte regeneration 27  Pathogenesis inflammatory cells, epithelium, endothelium cytokines, growth factors stimulate fibroblastic activity myofibroblasts secrete extracellular matrix resistance of fibroblasts to apoptosis (TGF-β) organisation leading to interstitial fibrosis 28  Honeycomb lung - pathogenesis ▪ end-stage chronic interstitial fibrosis - any cause ▪ commonest causes ▪ idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) ▪ extrinsic allergic alveolitis ▪ sarcoidosis ▪ morphology ▪ cystic air spaces with coalescence ▪ dilated bronchi and alveoli ▪ septal fibrosis and inflammation ▪ focal squamous metaplasia ▪ smooth muscle proliferation round terminal bronchioles 29 Complications Outcome fibrosis greatly reduces pulmonary capillary network, leading to pulmonary hypertension RVH R heart failure (cor pulmonale) Prognosis mild focal fibrosis 10% recovery, minimal residual respiratory dysfunction marked interstitial fibrosis / honeycomb lung death due to respiratory and cardiac failure 20% death due to chronic severe respiratory impairment 70% death in acute phase 30  Extrinsic Allergic Alveolitis ▪ Hypersensitivity pneumonitis ▪ caused by an immune reaction to inhaled antigens ▪ defect in antigen specific T lymphocyte suppressor function ▪ bird fanciers' lung - budgerigar and pigeon serum and faeces ▪ animal handlers’ lung - animal proteins - dander (skin squames, fur, hair), urine ▪ farmers' lung - micropolyspora faeni in mouldy hay ▪ microbial antigens - thermophilic bacteria and fungi that contaminate rotting crops – hay & 31 compost  Extrinsic Allergic Alveolitis ▪ acute exposure to antigen ▪ type III hypersensitivity response ▪ immune complexes at site of allergen entry in the lung activate complement with resulting inflammation ▪ dyspnoea, fever and cough 4-8 hours after exposure to antigen, resolving after 12-24 hours 32 ▪ chronicExtrinsic Allergic Alveolitis pulmonary fibrosis ▪ repeated exposure to antigen ▪ Type IV cell mediated hypersensitivity reaction ▪ small granulomas in 70% ▪ many interstitial lymphocytes ▪ scanty neutrophils, eosinophils, mast cells ▪ interstitial fibrosis ▪ insidious onset of cough and dyspnoea ▪ eventually honeycomb lung in 5% of cases 33 DISEASE LAVAGE CELL COUNT Extrinsic Lymphocytes 70%🡻 T4:T8 N/🡻 Allergic Slight increase in neutrophils & Alveolitis eosinophils Mast cells present NORMAL Neutrophils - up to 3% (5% in smokers) Eosinophils - up to 0.5% Lymphocytes - up to 15% T4:T8 – 0.9-3.6 Langerhans cells (antigen presenting dendritic cells of airways) - 4% in smokers Rest macrophages 34  Asbestos Asbestos related disease ▪ Occupational exposure ▪ mining and refining asbestos ▪ exposure - in building industry and where asbestos used for insulation - dockyards ▪ Risk of disease depends on ▪ duration (long exposure increases risk) ▪ intensity ▪ type of asbestos (fibres over 8mm long cause disease) - blue and brown asbestos fibres persist 35  Asbestos Related Disease ▪ pleural plaques - benign plaques of collagen ▪ pleural effusions and pleural thickening ▪ asbestosis - interstitial fibrosis of lungs, in early stage: maximal at lung bases ▪ malignant mesothelioma ▪ carcinoma of the lung ▪ long latent period of up to 50 years between exposure and clinical onset of disease ▪ asbestos bodies 36 Pleural Plaques 37  Asbestosis ▪ Chest X-ray ▪ Lung function tests: restrictive pattern 38  mesothelioma Asbestos Related Disease asbestosis 39  Asbestos bodies ▪ Asbestos bodies ▪ long thin fibres coated with haemosiderin and protein to form brown filaments with a bead or drumstick pattern ▪ also present in sputum 40