Interstitial Lung Disease Prof. FA Carey

Pulmonary interstitium r Alveolar lining cells (types 1 and 2) r Thin elastin-rich connective component containing capillary blood vessels

Interstitial lung disease r Early stage is alveolitis (injury with inflammatory cell infiltration) r Late stage characterised by fibrosis Clinical effects due to hypoxia (respiratory failure) and cardiac failure

Causes…. r Environmental (minerals, drugs, radiation. Post-ARDS) l Hypersensitivity (mouldy hay, avian proteins) r Unknown (idiopathic) l Connective tissue diseases l Fibrosing alveolitis Diagnosis based on clinical features often with biopsy

Biopsy in interstitial lung disease… r Transbronchial biopsy – special forceps used at bronchoscopy r Thoracoscopic biopsy – more invasive but more reliable and generates far more tissue

Chronic Interstitial Disease r Fibrosing alveolitis r Sarcoidosis r Extrinsic allergic alveolitis (hypersensitivity pneumonitis) r Pneumoconiosis r Connective tissue diseases

Fibrosing Alveolitis r aka cryptogenic fibrosing alveolitis (CFA), usual interstitial pneumonia (UIP) r Progressive interstitial fibrosis of unknown cause r Variable associated inflammation r Finger clubbing

Pathology r Subpleural and basal fibrosis r Inflammatory component variable r Terminally lung structure replaced by dilated spaces surrounded by fibrous walls

Fibrosing alveolitis (early)

Fibrosing alveolitis (late – honeycombing)

Honeycombing – basal/subpleural (a splint!)

Extrinsic allergic alveolitis (hypersensitivity pneumonitis) r Chronic inflammatory disease l Small airways l Interstitium l Occasional granulomas r Allergic origin l Type III hypersensitivity l Type IV hypersensitivity

EAA – inflammatory interstitial expansion

EAA - granuloma

Causes of EAA r Thermophilic bacteria – Farmers lung r Avian proteins – Bird fanciers lung r Fungi – Malt workers lung Precipitins (antibodies) often detectable in serum. Unusual cases come to biopsy.

Sarcoidosis r Multisystem granulomatous disorder of unknown cause (defined by histological means) r Pulmonary involvement is common r Most cases mild and self-limiting

Other manifestations of sarcoidosis r Uveitis (inflammation of iris) r Erythema nodosum r Lymphadenopathy r Hypercalcaemia

Transbronchial biopsy - sarcoidosis

Sarcoidosis - granuloma

Apical scarring in sarcoidosis

Sarcoid – scarring and burnt-out granulomas

Sarcoid - granulomas

Pulmonary involvement in connective tissue diseases r Interstitial fibrosis (milder than fibrosing alveolitis) r Pleural effusions r Rheumatoid nodules

Rheumatoid nodule

Pneumoconiosis Lung disease caused by mineral dust exposure Asbestosis Coal workers lung Silicosis

Thin whole mount section of a coal-workers lung (unstained)

Coal miner with progressive massive fibrosis (unstained)

Disease depends on….  Particle size (1-5  m) r Reactivity of particle r Clearance of particle r Host response

Asbestos r A silicate r Serpentine (curved) asbestos fibres relatively safe r Straight (amphibole) asbestos highly dangerous

Asbestos… r Parietal pleural plaques r Interstitial fibrosis (asbestosis) r Bronchial carcinoma r Mesothelioma

Asbestosis bodies (from human lung)

Association of asbestos bodies with fibrosis (asbestosis)

Pleural plaque on diaphragm