Interstitial Lung Disease — Types, Causes, Diagnosis & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Interstitial lung disease (ILD) is an umbrella term encompassing more than 200 heterogeneous conditions characterised by diffuse inflammation and/or fibrosis (scarring) of the lung parenchyma — specifically affecting the alveolar walls, the alveolar epithelium, the capillary endothelium, and the spaces between these structures (the interstitium). The result is progressive loss of lung compliance (stiffness), impaired gas exchange, and restrictive ventilatory defect. The major ILD categories are: idiopathic interstitial pneumonias (IIPs) — including idiopathic pulmonary fibrosis (IPF) the most common and most lethal IIP, non-specific interstitial pneumonia (NSIP), cryptogenic organising pneumonia (COP), respiratory bronchiolitis-ILD, and desquamative interstitial pneumonia (DIP); connective tissue disease-associated ILD (CTD-ILD — occurring in systemic sclerosis, rheumatoid arthritis, inflammatory myositis, Sjögren's syndrome, and SLE); hypersensitivity pneumonitis (HP — immune-mediated ILD from chronic inhalational antigen exposure — farmer's lung, bird fancier's lung); sarcoidosis; occupational ILDs (pneumoconiosis — silicosis, asbestosis, coal workers' pneumoconiosis); drug-induced ILD (amiodarone, methotrexate, nitrofurantoin, immune checkpoint inhibitors); and rare ILDs (lymphangioleiomyomatosis, pulmonary alveolar proteinosis, Langerhans cell histiocytosis). Accurate subtype classification is essential because it determines treatment, prognosis, and monitoring — requiring multidisciplinary team (MDT) assessment by a respiratory physician, radiologist, and pathologist.

ILD causes vary markedly by subtype, and identifying the underlying aetiology is crucial for targeted treatment. Idiopathic causes (when no trigger is identified): IPF — the most common ILD; primarily affects men over 60; pathogenesis involves repeated microinjuries to alveolar epithelium (type II pneumocytes) triggering aberrant fibroblast activation and collagen deposition; genetic susceptibility (MUC5B promoter variant present in 35% of IPF patients vs 9% of controls; TERT and TERC mutations — telomere shortening — in familial IPF); smoking is the strongest modifiable risk factor (80% of IPF patients are current or former smokers); gastro-oesophageal reflux (micro-aspiration) is a proposed contributing mechanism. Connective tissue diseases (CTD): systemic sclerosis causes ILD in 40-60%, particularly the NSIP pattern; rheumatoid arthritis causes ILD in 10-20% (UIP pattern carries worst prognosis); inflammatory myositis (dermatomyositis, polymyositis — anti-Jo-1, anti-MDA5, anti-SAE antibodies predict ILD) — rapidly progressive ILD in anti-MDA5-positive dermatomyositis carries high mortality. Hypersensitivity pneumonitis: inhalation of organic antigens — avian proteins (bird fancier's lung — most common UK HP), thermophilic actinomycetes from mouldy hay (farmer's lung), hot tub lung (Mycobacterium avium complex), and isocyanates (industrial HP); chronic exposure causes progressive fibrosis indistinguishable from IPF on histology and HRCT. Drugs: methotrexate (acute eosinophilic pneumonitis), amiodarone (phospholipidosis), nitrofurantoin, bleomycin, and immune checkpoint inhibitors (pneumonitis in 3-8% of anti-PD-1 therapy). Occupational exposures: asbestos (asbestosis — dose-related; also mesothelioma risk), silica dust (silicosis — stonemasons, miners), coal dust. Radiation-induced pneumonitis (following thoracic radiotherapy — latency 6 weeks to 6 months).

ILD typically presents insidiously — patients often attribute early symptoms to ageing, deconditioning, or smoking. Dyspnoea on exertion (breathlessness with activity): the cardinal symptom — initially present only with vigorous exertion, progressively worsening over months to years (in IPF) or rapidly over weeks (in acute interstitial pneumonia, acute exacerbations of IPF, anti-MDA5-positive DM-ILD); most patients present at MRC dyspnoea grade 3-4 when first diagnosed. Dry non-productive cough: persistent, irritating cough — a dominant symptom in IPF and hypersensitivity pneumonitis; may respond partially to cough suppressants (codeine, pregabalin) but difficult to control. Fatigue: profound, not proportionate to dyspnoea grade — contributes significantly to functional impairment. On physical examination: bilateral fine end-inspiratory ('velcro') crackles at the lung bases — characteristic of IPF and other fibrotic ILDs; heard in 90%+ of IPF patients; absent or less prominent in HP. Finger clubbing: present in 25-50% of IPF patients — a sign of significant lung remodelling; less common in other ILDs. Cyanosis: central cyanosis at rest indicates advanced disease with severe hypoxaemia. Features suggesting CTD-ILD: Raynaud's phenomenon, skin thickening, joint swelling, muscle weakness, skin rash (heliotrope — dermatomyositis), mechanic's hands, sicca symptoms. Features suggesting hypersensitivity pneumonitis: occupational or avian exposure history; temporal relationship between symptoms and exposure (worse during work week, improved on holiday — occupational HP).

ILD diagnosis requires multidisciplinary team (MDT) assessment — integrating clinical history, pulmonary function tests, HRCT findings, BAL results, and histopathology where obtained. ILD MDTs at specialist centres have been shown to significantly improve diagnostic accuracy. Pulmonary function tests (PFTs): restrictive ventilatory defect (reduced FVC with FEV1/FVC ratio preserved or elevated), reduced total lung capacity (TLC), and critically — reduced diffusing capacity for carbon monoxide (DLCO/transfer factor TF) — reflecting impaired gas exchange; in IPF, FVC and DLCO decline over 12 months are the primary endpoints in antifibrotic trials and predict mortality. 6-minute walk test (6MWT): assesses exercise tolerance and exertional oxygen desaturation — 6MWT distance and O2 saturation nadir are important functional and prognostic markers. HRCT of the chest (high-resolution CT without contrast): the most important non-invasive investigation — identifies the pattern of ILD. UIP pattern (usual interstitial pneumonia — basal, subpleural honeycombing ± traction bronchiectasis, without ground-glass or consolidation) in the correct clinical context allows IPF diagnosis without biopsy (per ATS/ERS/JRS/ALAT 2022 guidelines); NSIP pattern — bilateral ground-glass opacity, subpleural sparing, lower zone predominance; HP pattern — fibrosis in mid-upper zones, air-trapping on expiratory views, centrilobular nodules; COP — consolidation and ground-glass opacity in bronchocentric distribution. Bronchoscopy with BAL: CD4/CD8 ratio (sarcoidosis — elevated), lymphocytosis (HP, NSIP, COP), eosinophilia; transbronchial lung biopsy (TBLB) has limited yield in fibrotic ILD; transbronchial cryobiopsy achieves larger specimens than forceps biopsy with lower complication rates. Surgical lung biopsy (VATS or open): performed when HRCT pattern is indeterminate and histological diagnosis changes management; high complication rate in advanced IPF (acute exacerbation triggered by biopsy). Blood tests: ANA, anti-dsDNA, Scl-70, anti-Ro/La, anti-Jo-1, anti-MDA5, RF, CCP, myositis panel (for CTD-ILD); serum precipitins (avian, thermophilic actinomycetes — for HP); KL-6 (Krebs von den Lungen-6 — elevated in fibrotic ILD, useful for monitoring).

Treatment depends critically on ILD subtype — treating all ILDs the same is harmful (corticosteroids improve COP and CTD-ILD but worsen IPF). Idiopathic pulmonary fibrosis (IPF): antifibrotic therapy slows decline but does not reverse established fibrosis. Nintedanib (Ofev — 150 mg BD): tyrosine kinase inhibitor targeting VEGFR, FGFR, and PDGFR — reduces FVC decline rate by 50% (INPULSIS trials); main side effects are diarrhoea (60%), nausea, and hepatotoxicity (LFT monitoring required). Pirfenidone (Esbriet — 2403 mg/day in divided doses): TGF-beta inhibitor — reduces FVC decline by approximately 50% (CAPACITY and ASCEND trials); side effects include photosensitivity (sun protection essential), GI upset, and fatigue. Both agents are recommended by NICE for mild-to-moderate IPF (FVC above 50%); both slow but do not halt progression. Anti-acid therapy (PPIs or H2 blockers): NICE recommends for IPF due to micro-aspiration contribution. Hypersensitivity pneumonitis: antigen avoidance is the primary and most effective treatment — identification and elimination of the causative exposure (remove the bird, replace the hot tub, use respiratory protection in occupational HP); prednisolone 40-60 mg/day for 4-8 weeks for acute exacerbations — tapering over 3-6 months; if fibrosis established, antifibrotics (nintedanib has evidence in progressive fibrotic HP — INBUILD trial). CTD-ILD: immunosuppression — mycophenolate mofetil (MMF — 1-3 g/day — first-line for systemic sclerosis-ILD; SLS-II trial showing comparable to cyclophosphamide); rituximab (anti-CD20 — second-line for RA-ILD and SSc-ILD, and first-line for anti-MDA5 DM-ILD); nintedanib also approved for progressive fibrotic CTD-ILD. COP: responds dramatically to prednisolone 40-60 mg/day — 60-80% achieve complete radiological resolution; however, relapse on tapering is common (50-60%) — slow taper over 6-12 months. Sarcoidosis: observation for asymptomatic mild disease; prednisolone for progressive disease. Pulmonary rehabilitation: essential for all fibrotic ILD — improves exercise tolerance, quality of life, and 6MWT distance. Long-term oxygen therapy (LTOT): for resting PaO2 below 7.3 kPa or SpO2 below 88%. Lung transplantation: definitive treatment for end-stage ILD — IPF, SSc-ILD, and chronic HP account for the majority of transplants in the ILD category; 5-year post-transplant survival approximately 50-60%; bilateral lung transplant preferred; post-transplant survival for ILD comparable to COPD. Acute exacerbation of IPF (AE-IPF): high-dose methylprednisolone (500-1000 mg IV for 3 days) often used despite lack of strong evidence; cyclophosphamide, broad-spectrum antibiotics (exclude infection), and supportive care including NIV/mechanical ventilation (recognising poor prognosis of AE-IPF with invasive ventilation — 50-80% in-hospital mortality).

ILD — particularly IPF and other progressive fibrotic ILDs — causes serious complications as the disease advances. Acute exacerbation (AE-IPF): a catastrophic complication characterised by rapid deterioration of breathlessness over days to weeks (acute dyspnoea, new bilateral ground-glass opacities on HRCT superimposed on existing fibrosis, excluding identifiable triggers); in-hospital mortality is 50-80%; triggers include viral infections, surgical procedures, and BAL — may be idiopathic; AE-IPF accounts for 40-50% of IPF deaths. Respiratory failure: progressive loss of gas exchange capacity leads to type 1 respiratory failure (hypoxaemia, normal or low PaCO2) — requiring supplemental oxygen, then high-flow nasal oxygen, then NIV in end-stage disease. Pulmonary hypertension (PH): complicates up to 40% of IPF patients with advanced fibrosis — caused by hypoxic pulmonary vasoconstriction and vascular remodelling; worsens dyspnoea out of proportion to lung function, limits 6MWT, and significantly worsens prognosis; PAH-specific therapy (sildenafil, ambrisentan) does not improve outcomes in PH-ILD. Lung cancer: IPF patients have 7-14-fold increased risk of lung cancer (predominantly adenocarcinoma and squamous cell carcinoma) — CT surveillance is essential; treatment is limited by poor lung function. Pneumothorax: honeycomb cysts in IPF can rupture — spontaneous pneumothorax in the context of severe ILD carries high mortality due to inability to tolerate further lung volume reduction. Secondary infections: immunosuppressed CTD-ILD patients are vulnerable to opportunistic infections including Pneumocystis jirovecii pneumonia (PJP — prophylaxis with co-trimoxazole recommended with combination immunosuppression) and fungal infections.

Preventable ILDs offer the greatest opportunity for intervention. Occupational ILD prevention: strict implementation of workplace exposure controls for silica dust (stonemasons, sandblasters, miners — enforced dust limits, water suppression, respiratory protection); asbestos — complete ban in the UK since 1999; surveillance spirometry and HRCT for workers with known silica or asbestos exposure. Hypersensitivity pneumonitis prevention: antigen avoidance is the only proven preventive measure — identify and eliminate the causative exposure before fibrosis develops (recurrent acute HP from continued exposure progresses to chronic fibrotic HP). Smoking cessation: reduces IPF risk and slows progression in established IPF. Drug-induced ILD monitoring: regular lung function assessment and chest radiography for patients on amiodarone, methotrexate, bleomycin, and immune checkpoint inhibitors — baseline HRCT before initiating potentially pneumotoxic therapies in patients with pre-existing lung disease. CTD-ILD monitoring: regular spirometry (FVC, DLCO) at 6-12-monthly intervals for patients with systemic sclerosis, RA, and inflammatory myositis — allows early detection and intervention before significant fibrosis develops. Vaccination: influenza and pneumococcal vaccination in all ILD patients; COVID-19 vaccination — COVID-19 causes ILD exacerbations; avoid live vaccines in immunosuppressed patients. Pulmonary rehabilitation and exercise maintenance — decline in 6MWT distance predicts mortality and is a target for ongoing physical therapy.

See a GP and request urgent referral to a respiratory physician or ILD specialist for: unexplained progressive breathlessness on exertion in a patient over 50, particularly with bilateral basal crackles ('velcro' crackles) on auscultation; a dry persistent cough lasting more than 8 weeks in a non-smoker; bilateral interstitial changes on chest X-ray of unknown cause; and breathlessness in a patient with a known connective tissue disease (systemic sclerosis, RA, inflammatory myositis). Seek emergency assessment (A&E) for: acute severe worsening of breathlessness in a patient with known ILD — this may represent an acute exacerbation of IPF, pneumonia, pulmonary embolism, or pneumothorax requiring urgent HRCT and treatment; severe hypoxaemia (SpO2 below 88% at rest on room air); and haemoptysis in an ILD patient (may indicate lung cancer complication). Contact your ILD specialist promptly for: any accelerated decline in breathlessness over days to weeks in a patient with established ILD; a 10% or more fall in FVC or DLCO on serial monitoring (indicates significant progression requiring treatment escalation); and new cough, fever, or purulent sputum in immunosuppressed ILD patients (infection or drug toxicity). Occupational exposure review: workers in stone-cutting, mining, or other dusty industries who develop cough and breathlessness should be referred urgently for spirometry and HRCT to exclude occupational ILD before further exposure causes irreversible damage.