Interstitial Lung Diseases

See Pulmonary Sarcoidosis for the full sarcoidosis page.

Overview

A group of >200 disorders sharing inflammation (pneumonitis) and fibrosis of the interalveolar septum — a non-specific lung reaction to injury, which may include a hypersensitivity reaction to an antigen.

Illness script: chronic dyspnoea + dry cough + fine crackles at the lung bases (± digital clubbing) ± normal percussion note.

Classification:

• Idiopathic interstitial pneumonias (e.g. idiopathic pulmonary fibrosis)
• Granulomatous ILD (e.g. sarcoidosis, hypersensitivity pneumonitis)
• ILD with known associations (drug/occupational exposures, connective tissue disease)
• Miscellaneous ILD

Risk factors / history clues

• Age — median age of IPF diagnosis is 67; younger patients presenting with an IPF-like picture raise suspicion of familial IPF or sarcoidosis.
• Sex — pulmonary lymphangioleiomyomatosis occurs only in females.
• Drug history — over 350 drugs are associated with lung fibrosis; amiodarone and cytotoxic/oncology drugs are the classic culprits, but also leflunomide, methotrexate, nitrofurantoin and some biological DMARDs.
• Occupational history — dusts including coal, asbestos, silica (see Occupational Lung Disease).
• Environmental exposure — birds, mouldy hay/compost/sugar cane, formaldehyde, spas (hypersensitivity pneumonitis triggers).
• Smoking history — eosinophilic pneumonia, respiratory bronchiolitis-ILD and IPF are all more common in smokers.
• Connective tissue disease — rheumatoid arthritis, scleroderma, polymyositis; also ask about rashes, arthralgia, radiotherapy history.
• GORD — may contribute to lung fibrosis and to acute exacerbations of established fibrotic disease. Despite this association, the guideline states that conditional recommendations were made against antacid medication and antireflux surgery for the treatment of IPF — treating GORD does not appear to alter the fibrotic disease course itself.
• Family history — e.g. short-telomere-associated IPF.
• Comorbidities — venous thromboembolism and hypothyroidism, alongside GORD, were associated with an increased risk of IPF, following a study of 22 comorbidities. Correspondingly, IPF was associated with a higher risk of lung cancer, but a reduced risk of hypertension. Malnutrition is under-recognised: in a study of 301 patients with IPF, 113 (37.5%) had malnutrition-related risk (GNRI <98) which resulted in an increased risk of mortality and discontinuation of therapy.

Examination

Cyanosis, digital clubbing; fine inspiratory crackles at the lung bases with faint breath sounds; resting SpO2 may be reduced in severe disease, and may drop further on exertion (e.g. sit-to-stand test); peripheral connective tissue disease features (joint deformity/swelling, sclerodactyly, rashes).

Investigations

• Bloods: baseline bloods, ANA, serum ACE, CK, rheumatoid factor, anti-CCP antibody, serum calcium.
• PFTs: restrictive pattern (↓FEV1, ↓FVC, normal/high FEV1/FVC ratio); reduced gas transfer factor (DLCO).
• CXR: reticular pattern most common; can also show ground-glass/nodular change; excludes pneumonia.
• Echo: to exclude left heart failure as a mimic.
• HRCT: may show honeycombing; the idiopathic pattern is classically subpleural- and basal-predominant with reticular abnormalities ± traction bronchiectasis.
• Advanced/specialist investigations: bronchoalveolar lavage, EBUS, VATS lung biopsy.

Idiopathic pulmonary fibrosis (IPF)

The most common ILD. Presents in older adults with slowly progressive dyspnoea over months to years. CXR shows reticulonodular shadowing; HRCT shows progressive reticular change. Historically a poor prognosis (median survival 3–5 years untreated).

Treatment: pulmonary rehabilitation; corticosteroids for acute exacerbations; symptom control (e.g. opioids for dyspnoea); antifibrotic therapy (pirfenidone, nintedanib — see the guideline-update box below); lung transplant if young/suitable; early referral to palliative care alongside disease-directed treatment, not only at the end stage. In practice, antifibrotic uptake is low even where funded — one large veteran cohort found among 14,792 veterans with IPF, 17% received antifibrotics. There was lower uptake associated with female sex, Black race and rural residence. Palliative care referral is similarly under-used despite the guidance above: ILD patients often complain of dyspnoea and cough, but only 25% are referred to a PC team.

Hypersensitivity pneumonitis (extrinsic allergic alveolitis)

Widespread diffuse inflammation of the small airways/alveoli from inhaled allergens.

Common causes: farmer’s lung (mouldy hay/grain/straw), bird fancier’s lung (avian droppings/feathers), hot-tub lung (Mycobacterium avium complex), and others (coffee dust, mushroom compost, prawn fumes, mouldy barley, rat urine, silkworms, cheese moulds, mouldy sugar cane fibres).

Illness script: acute/subacute pyrexia, chills, malaise, dyspnoea and neutrophilia several hours after allergen exposure. Repeated exposure drives fibrosis — progressive exertional dyspnoea, dry cough, fine crackles.

Treatment: allergen avoidance is paramount. For acute/severe/progressive disease: prednisolone 0.5 mg/kg (max 50 mg) for a minimum of 4 weeks. Fibrotic hypersensitivity pneumonitis (FHP) — the chronic, progressive pattern that develops with repeated exposure — is an irreversible lung disease with a high morbidity and mortality. A trial found the safety and effect of pirfenidone on disease progression in FHP demonstrated no significant between-group difference in FVC% at week 52, but was safe and improved progression free survival, suggesting a possible antifibrotic role once fibrosis is established rather than only in IPF.

Drug-induced ILD

Alveolitis without fibrosis is seen with amiodarone and cytotoxic drugs. Eosinophilic reactions (probably allergic) are seen with antibiotics, NSAIDs, antidepressants, antiepileptics, and cytotoxic drugs.

Pneumoconiosis

Dust accumulation in the lungs with a subsequent fibrotic reaction — see Occupational Lung Disease for the full current picture (this section previously covered coal, silica, metallic iron oxide and asbestos exposures; silicosis specifically now has its own dedicated page given the recent engineered-stone epidemic).

Asbestosis shows characteristic calcified pleural plaques on imaging and takes 10–20 years to develop; mesothelioma takes 20–40 years, is commonly complicated by pleural effusion, and carries a very poor prognosis.

Managing established ILD

• Referral to a respiratory physician to confirm diagnosis.
• Pulmonary rehabilitation.
• Symptom control: treat GORD, opioids for dyspnoea, corticosteroids for acute exacerbations.
• Long-term oxygen therapy usually required in advanced disease.
• Manage complications: annual influenza + pneumococcal vaccination, osteoporosis surveillance, timely antibiotics for infection, sleep- disordered breathing (nocturnal oxygen or CPAP), pulmonary hypertension (supplemental oxygen, diuretics, vasodilator therapy where indicated).