Interstitial Lung Disease

Interstitial lung disease (ILD) is a heterogeneous group of over 200 diffuse parenchymal lung disorders with inflammation and fibrosis of the interstitium, leading to restrictive physiology and impaired gas exchange.

Main groups

• Idiopathic interstitial pneumonias: idiopathic pulmonary fibrosis (UIP), nonspecific interstitial pneumonia, cryptogenic organising pneumonia, desquamative interstitial pneumonia, respiratory bronchiolitis ILD, acute interstitial pneumonia, lymphoid interstitial pneumonia.
• Connective tissue disease ILD: systemic sclerosis, rheumatoid arthritis, myositis and antisynthetase syndrome, Sjögren, lupus, mixed connective tissue disease.
• Exposure related: hypersensitivity pneumonitis, pneumoconioses (asbestos, silica), drug induced (amiodarone, methotrexate, nitrofurantoin, bleomycin, checkpoint inhibitors), radiation.
• Granulomatous: sarcoidosis.
• Others: eosinophilic pneumonias, pulmonary alveolar proteinosis, Langerhans cell histiocytosis, lymphangioleiomyomatosis, vasculitis.
• Incidence of fibrosing ILD is about 10 to 70 per 100,000, increasing with age. Progressive pulmonary fibrosis is defined by physiological, symptomatic or radiological worsening within a year despite treatment.
• Risk factors: smoking, occupational and environmental exposures, family history (telomerase mutations), gastro oesophageal reflux, autoimmunity, medications.
• Complications: respiratory failure, pulmonary hypertension, acute exacerbations, lung cancer, mortality (median survival 3 to 5 years in IPF).

• Progressive exertional dyspnoea and dry cough over months, fatigue, weight loss.
• Bibasal fine end inspiratory "Velcro" crackles, digital clubbing, signs of pulmonary hypertension.
• Extra thoracic features: Raynaud, skin tightening, mechanic hands, arthritis, sicca symptoms, rash, myalgia.
• Exposure history (birds, mould, hot tubs, metals, dusts), medications, family history.

• High resolution CT: patterns UIP (basal subpleural honeycombing, traction bronchiectasis), probable UIP, NSIP (ground glass with subpleural sparing), hypersensitivity pneumonitis (mosaic attenuation, air trapping, centrilobular nodules), organising pneumonia.
• Pulmonary function tests: restriction (FVC reduced), reduced DLCO; six minute walk test with desaturation.
• Serology: ANA, rheumatoid factor, anti CCP, anti Scl 70, anti centromere, myositis panel, ANCA, ENA (Ro, La), CK, precipitins for HP.
• Bronchoalveolar lavage (lymphocytosis suggests HP or NSIP; eosinophils suggests eosinophilic pneumonia), transbronchial cryobiopsy, surgical lung biopsy when HRCT is non diagnostic.
• Multidisciplinary discussion with radiology and pathology establishes the diagnosis.
• Echocardiography for pulmonary hypertension; baseline oxygen assessment.

• Remove exposures; stop causative drugs; smoking cessation; treat reflux.
• Idiopathic pulmonary fibrosis and progressive fibrosing ILD: nintedanib 150 mg twice daily or pirfenidone 801 mg three times daily (slow FVC decline by about 50%); manage diarrhoea (loperamide) and hepatotoxicity; avoid prednisolone/azathioprine/N acetylcysteine combination (harmful).
• Inflammatory ILD (NSIP, CTD ILD, HP, organising pneumonia): prednisolone 0.5 to 1 mg/kg tapered, with steroid sparing mycophenolate mofetil 1 to 1.5 g twice daily or azathioprine 2 mg/kg; rituximab 1 g on days 1 and 15 or cyclophosphamide for severe or progressive disease; tocilizumab 162 mg SC weekly in systemic sclerosis ILD.
• Pneumocystis prophylaxis (co trimoxazole 960 mg three times weekly) with prolonged immunosuppression; bone protection.
• Supportive: long term oxygen therapy for resting PaO2 55 mmHg or less; pulmonary rehabilitation; vaccinations; palliative care and opioids (morphine 2.5 to 5 mg) for refractory breathlessness; inhaled treprostinil for ILD with pulmonary hypertension.
• Acute exacerbation: methylprednisolone 500 to 1000 mg IV for 3 days, broad antibiotics, oxygen or high flow, avoid invasive ventilation when no transplant option.
• Lung transplantation referral for patients under 65 to 70 with progressive disease (DLCO under 40%, FVC decline); antifibrotics may continue.
• Monitor FVC and DLCO every 3 to 6 months.