Interstitial Lung Disease

Interstitial Lung Disease 7 marks Pathy's does not carry a dedicated ILD chapter; ILD appears within the COPD differential diagnosis (Table 42.3), the muscle disorders chapter (anti-synthetase syndrome and dermatomyositis-associated ILD) and the pulmonary rehabilitation chapter. The points below combine that textbook material with current ATS/ERS/JRS/ALAT guidance, as required for a complete answer.

Definition: a heterogeneous group of diffuse parenchymal lung diseases in which inflammation and/or fibrosis affect the alveolar interstitium, producing a restrictive ventilatory defect with impaired gas transfer. ILD is predominantly a disease of older adults — idiopathic pulmonary fibrosis (IPF) is typically diagnosed between 60 and 70 years.

Classification: (a) known cause — occupational/environmental (asbestosis, silicosis, coal worker's pneumoconiosis, hypersensitivity pneumonitis from birds, mould, and in India bagassosis and farmer's lung), drugs (amiodarone, methotrexate, nitrofurantoin, bleomycin, immune checkpoint inhibitors) and radiation; (b) connective tissue disease-associated — rheumatoid arthritis, systemic sclerosis, Sjögren's, and dermatomyositis/polymyositis (the anti-synthetase syndrome: acute myopathy, Raynaud's, ILD, mechanic's hands and anti-Jo-1 antibody); (c) idiopathic interstitial pneumonias — IPF, NSIP, COP, RB-ILD, DIP; (d) granulomatous — sarcoidosis; (e) others — lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis. In India, post-tuberculous fibrosis is an important mimic.

Clinical features: insidious progressive exertional dyspnoea and a dry cough; fine end-inspiratory "Velcro" crackles at the bases; digital clubbing (about half of IPF cases); later cyanosis and signs of cor pulmonale. Search deliberately for extrapulmonary clues — arthritis, sclerodactyly, Raynaud's phenomenon, Gottron's papules, heliotrope rash, dry eyes and mouth.

Distinguishing ILD from COPD and heart failure (Pathy's Table 42.3): ILD gives a dry cough with fine basal crackles, a restrictive spirometry pattern and impaired diffusing capacity (TLCO), with B-line artefacts on chest ultrasound; COPD gives obstruction with hyperinflation; kyphoscoliosis gives restriction with a normal diffusing capacity. Always ask about industrial exposure and drug toxicity.

Investigations: HRCT chest is central — a usual interstitial pneumonia (UIP) pattern (basal and subpleural reticulation with honeycombing and traction bronchiectasis, minimal ground glass) in the right clinical setting confirms IPF without biopsy. Pulmonary function shows reduced FVC, reduced TLC, preserved or raised FEV1/FVC and reduced TLCO. Add an autoimmune panel (ANA, RF, anti-CCP, myositis panel), a hypersensitivity pneumonitis exposure history and precipitins, six-minute walk test with oximetry, and echocardiography for pulmonary hypertension. Bronchoalveolar lavage and surgical or cryobiopsy are reserved for uncertain cases — and are often inappropriate in the frail elderly.

The multidisciplinary discussion (MDD) between clinician, radiologist and pathologist is the recognised diagnostic gold standard for ILD.

Management — general: remove the causative exposure or drug; smoking cessation; treat gastro-oesophageal reflux and obstructive sleep apnoea; vaccination; supplemental oxygen for resting or exertional hypoxaemia; pulmonary rehabilitation — Pathy's cites Dowman et al. (Thorax 2017) showing clinically important improvements in six-minute walk distance, symptoms and quality of life after exercise training in ILD; treat cough and breathlessness palliatively (opioids); consider transplantation only in highly selected younger patients.

Management — disease-specific: IPF is treated with antifibrotics, not steroids — pirfenidone or nintedanib slow the rate of FVC decline. Immunosuppression is harmful in IPF (PANTHER-IPF) but is the mainstay in connective tissue disease-ILD, hypersensitivity pneumonitis and sarcoidosis (corticosteroids with mycophenolate, azathioprine or rituximab). Nintedanib is licensed for systemic sclerosis-ILD (SENSCIS) and for progressive fibrosing ILD (INBUILD).

Prognosis: IPF is the most aggressive form — median survival about 3–5 years from diagnosis, worse than many cancers. Acute exacerbations of IPF carry very high mortality. Death is usually from progressive respiratory failure, acute exacerbation, pulmonary hypertension or lung cancer.

Geriatric considerations: comorbidity is the rule (emphysema in the combined pulmonary fibrosis and emphysema (CPFE) syndrome, coronary disease, pulmonary hypertension, reflux, lung cancer); antifibrotic drugs cause diarrhoea, nausea, weight loss and deranged liver function, all poorly tolerated in frail patients; and early advance care planning and palliative care referral are essential given the prognosis. Latest Updates and Current Practice (2023–Present) Nerandomilast (Jascayd) — a preferential phosphodiesterase-4B inhibitor with antifibrotic and immunomodulatory effects — was FDA-approved for IPF in October 2025 (the first new IPF drug in over a decade) and for progressive pulmonary fibrosis (PPF) in December 2025, on the strength of the FIBRONEER-IPF and FIBRONEER-ILD trials (NEJM 2025). In FIBRONEER-ILD the mean FVC decline at 52 weeks was −86 mL (18 mg) and −69 mL (9 mg) versus −152 mL with placebo; it worked both as monotherapy and added to nintedanib or pirfenidone, with better tolerability (mild diarrhoea) than nintedanib. "Progressive pulmonary fibrosis" (PPF) has replaced the older term "progressive fibrosing ILD" and is now a formal, treatable entity defined by worsening symptoms, physiology or radiology despite management of the underlying ILD — the 2022 ATS/ERS/JRS/ALAT criteria remain the standard. Current Practice Update — three points: (1) The textbook treats ILD only as a differential diagnosis of COPD; current practice recognises it as a treatable, antifibrotic-responsive disease in its own right. (2) Where Pathy's offers only pulmonary rehabilitation and supportive care, there are now three licensed antifibrotics — pirfenidone, nintedanib and nerandomilast. (3) Immunosuppression, once used empirically for "pulmonary fibrosis", is now contraindicated in IPF and reserved for autoimmune and inflammatory ILD.