Interstitial Lung Disease (ILD)

Definition

Interstitial lung disease (ILD) is an umbrella term for a diverse group of more than 200 disorders affecting the lung interstitium — the supporting tissue around the alveoli — through inflammation, scarring (fibrosis) or both. Idiopathic pulmonary fibrosis is one specific, progressive form; ILD as a whole is far broader, and the distinction matters because some forms are reversible with treatment while others are relentlessly progressive. Getting the subtype right is the single most consequential step in caring for these patients.

Pathophysiology

Injury and abnormal repair

An initial insult — inhaled antigen, autoimmune inflammation, dust, drug, radiation, or in idiopathic disease an unidentified trigger — damages the alveolar epithelium. In health, repair restores normal architecture. In ILD the repair process is dysregulated: fibroblasts are recruited and differentiate into myofibroblasts, collagen and extracellular matrix accumulate, and the delicate alveolar wall is replaced by scar.

The consequences for breathing

Thickened, scarred interstitium makes the lungs stiff. Compliance falls, so more pressure is needed for each breath, and patients adopt a rapid, shallow pattern that is mechanically efficient but increases dead-space ventilation. Lung volumes fall — the restrictive pattern — while the airways remain patent, which is why the FEV₁/FVC ratio is preserved or high.

Gas exchange and exertional hypoxaemia

The thickened alveolar–capillary membrane and the loss of capillary bed reduce diffusing capacity. At rest, oxygen may be normal; on exertion, transit time through the capillary falls and equilibration fails, producing the characteristic pattern of profound exertional desaturation with normal resting saturation. Resting oximetry therefore misses the problem entirely, and exercise testing is essential.

Inflammation versus fibrosis

This is the central therapeutic question. Inflammation-predominant disease responds to immunosuppression; fibrosis-predominant disease does not, and immunosuppression may cause harm. Many ILDs sit between the two, and a proportion of initially inflammatory disease develops a progressive pulmonary fibrosis phenotype that behaves like IPF regardless of its original cause — a concept that has reshaped treatment in the last decade.¹

Co-morbidities

ILD frequently coexists with the connective-tissue diseases that cause some forms, and with pulmonary hypertension, gastro-oesophageal reflux, obstructive sleep apnoea, coronary and cerebrovascular disease, lung cancer, osteoporosis (compounded by corticosteroid therapy), and the deconditioning, anxiety and depression that accompany progressive breathlessness. Emphysema coexisting with fibrosis produces a distinctive pattern with preserved lung volumes but severely reduced gas transfer and a high risk of pulmonary hypertension.

Prevalence

ILD is uncommon relative to asthma and COPD but not rare, and incidence rises steeply with age. The relative frequency of subtypes varies by population and referral pattern, with IPF and connective-tissue-disease-associated ILD among the more common in specialist practice, and hypersensitivity pneumonitis under-diagnosed because the causative exposure is not asked about. Diagnostic delay is a persistent problem — many patients are treated for asthma, COPD or heart failure for a year or more before ILD is considered.

Causes and risk factors

• Idiopathic interstitial pneumonias — including IPF and non-specific interstitial pneumonia (NSIP).
• Connective-tissue-disease-associated ILD — rheumatoid arthritis, systemic sclerosis, myositis, Sjögren syndrome, lupus and mixed connective tissue disease. ILD is sometimes the first manifestation, preceding joint or skin disease by years.
• Hypersensitivity pneumonitis — from inhaled organic antigens: birds and feather bedding, mould in damp housing or hot tubs, agricultural exposures. Identifying and removing the antigen can halt or reverse it, which makes the exposure history one of the highest-value parts of the consultation.
• Occupational and dust-related disease — asbestosis, silicosis including engineered-stone silicosis, coal worker’s pneumoconiosis; see occupational lung disease.
• Drug- and radiation-induced ILD — amiodarone, methotrexate, nitrofurantoin, bleomycin, immune checkpoint inhibitors and thoracic radiotherapy.
• Sarcoidosis and other granulomatous diseases.
• Smoking-related ILD, and genetic factors including telomere-related and surfactant protein gene variants, with familial clustering in a minority.

Symptoms

Typical features

• Progressive breathlessness on exertion — the dominant symptom, usually developing over months.
• A persistent, often distressing dry cough, which patients frequently rate as more disabling than the breathlessness.
• Fatigue and reduced exercise tolerance.
• Fine, dry “velcro” crackles at the lung bases, and finger clubbing in some subtypes.
• Features of an underlying connective tissue disease — Raynaud phenomenon, joint pain, rash, dry eyes and mouth, reflux, muscle weakness.

Why diagnosis is often delayed

Early breathlessness is attributed to age, weight or deconditioning, and resting oxygen saturation is normal. Bibasal crackles are frequently misread as heart failure or infection. A dry cough in a smoker is put down to smoking. The combination of exertional breathlessness, a dry cough and velcro crackles should prompt CT rather than a trial of inhalers.

Warning signs

Diagnosis

Why diagnosis matters

Because some ILDs are treatable or reversible while others are progressive, an accurate subtype diagnosis determines whether immunosuppression, antifibrotic therapy or trigger removal is appropriate — and giving the wrong one causes harm. Immunosuppression in IPF, for example, increases mortality. There is no substitute for getting the diagnosis right.²

How is it diagnosed?

Diagnosis rests on integrating clinical history, exposures, serology, high-resolution CT and, where needed, tissue — and is made at a specialist multidisciplinary meeting bringing together respiratory physicians, thoracic radiologists, pathologists and rheumatologists. This is not a bureaucratic step: multidisciplinary discussion changes the diagnosis in a substantial proportion of cases and is the accepted standard.

Radiology

High-resolution CT is central. It identifies the pattern — usual interstitial pneumonia with basal, subpleural reticulation, traction bronchiectasis and honeycombing; NSIP with ground-glass and relative subpleural sparing; hypersensitivity pneumonitis with mosaic attenuation and air trapping. A confident radiological pattern in the right clinical setting can make biopsy unnecessary.

Lung function

Spirometry and lung volumes show a restrictive pattern with reduced forced vital capacity and total lung capacity and a preserved or raised FEV₁/FVC ratio. Gas transfer (DLCO) is reduced, often disproportionately, and is the most sensitive measure of disease severity and progression. Six-minute walk testing with oximetry is essential to detect exertional desaturation that resting measures miss, and walk distance and nadir saturation both carry prognostic weight. Serial FVC and DLCO define progression and drive treatment decisions.

Exposure history and serology

A structured exposure history — birds including feather bedding and down, mould and water damage at home or work, hot tubs, farming, occupational dusts, all medications past and present, radiotherapy — is diagnostic in hypersensitivity pneumonitis and is the step most often done poorly.³ Autoimmune serology screens for connective tissue disease, and a rheumatology opinion is sought where features are suggestive even if serology is negative.

Bronchoscopy and biopsy

Bronchoalveolar lavage assists where hypersensitivity pneumonitis, sarcoidosis, infection or malignancy is considered. Surgical lung biopsy or transbronchial cryobiopsy is reserved for cases where the diagnosis remains uncertain after multidisciplinary discussion and where the result would change management — balanced against real procedural risk in a breathless patient.

Investigations for related conditions

Echocardiography screens for pulmonary hypertension, which is common and changes both prognosis and treatment. Assessment also covers reflux, sleep-disordered breathing, cardiovascular risk, bone density before prolonged corticosteroids, and lung cancer, for which fibrotic ILD is an independent risk factor.

Management

Management and goals

The goals are to identify and remove any reversible cause, suppress inflammation where it is driving the disease, slow fibrosis where it is not, maintain exercise capacity and function, treat cough and breathlessness, and support the person through what may be a progressive illness. Care is coordinated through a specialist ILD service, with parallel attention to rehabilitation, symptom control and, where appropriate, advance care planning from early on rather than at the end.

Removing the trigger

The highest-value intervention where it applies. Complete antigen avoidance in hypersensitivity pneumonitis — removing birds and feather bedding from the house, remediating mould, changing an occupational exposure — can halt and sometimes reverse the disease. Stopping a causative drug likewise. Half-measures do not work, and this often requires difficult conversations about pets, housing or work.

Immunosuppression

Appropriate for inflammatory and connective-tissue-disease ILD. In systemic sclerosis-associated ILD, mycophenolate mofetil was as effective as oral cyclophosphamide over two years and considerably better tolerated, making it the usual first choice.⁴ Corticosteroids are used, often with a steroid-sparing agent, but are avoided in IPF where they worsen outcomes.

Antifibrotic therapy

Nintedanib and pirfenidone slow the rate of FVC decline. Critically, benefit is not confined to IPF: in patients with progressive fibrosing ILD of any cause, nintedanib significantly slowed FVC decline compared with placebo,⁵ and it also slowed decline in systemic sclerosis-associated ILD.⁶ This has changed practice substantially — the question is no longer only “is this IPF?” but “is this progressing despite treatment?”

Pulmonary hypertension

Pulmonary hypertension complicating ILD carries a poor prognosis and was long untreatable. Inhaled treprostinil improved exercise capacity in pulmonary hypertension due to interstitial lung disease in a randomised trial, providing the first evidence-based option for this group.⁷

Oxygen therapy

Long-term oxygen is used for resting hypoxaemia. Ambulatory oxygen for exertional desaturation improved health-related quality of life and reduced breathlessness in patients with fibrotic ILD in a crossover randomised trial — a meaningful finding, since this group is frequently told oxygen will not help unless they are hypoxaemic at rest.⁸

Identifying deterioration

A fall in FVC of 10% or DLCO of 15% over a year defines progression and triggers treatment escalation. Acute exacerbation of ILD — rapid worsening over days to weeks with new ground-glass change and no alternative explanation — carries very high mortality and requires urgent hospital assessment. Any sudden deterioration should also prompt consideration of infection, pulmonary embolism, pneumothorax and heart failure.

Medications

Medications for ILD

Treatment is subtype-specific and guided by the multidisciplinary diagnosis: corticosteroids and steroid-sparing immunosuppressants such as mycophenolate, azathioprine or rituximab for inflammatory disease; antifibrotics for IPF and progressive fibrosing phenotypes. Cough is treated actively — it is frequently the most distressing symptom — with reflux management, and opioids or gabapentinoids in refractory cases.

Correct use of medications

Antifibrotics have predictable and manageable side effects: diarrhoea and hepatotoxicity with nintedanib, nausea and photosensitivity with pirfenidone, requiring liver monitoring, sun protection and often dose adjustment rather than discontinuation. Immunosuppressants require blood count and liver monitoring, infection vigilance, and vaccination before starting where possible. Reflux is treated because aspiration is implicated in progression.

What to avoid

Immunosuppression in IPF, high-dose corticosteroids as a default in fibrotic disease, and delaying antifibrotic therapy while awaiting further decline. Medications known to cause ILD are reviewed and stopped where they may be contributing.

Multi-system manifestations

Connective tissue disease

In CTD-associated ILD the lung is one organ among many: joints, skin, muscle, oesophagus, kidneys and blood vessels may all be involved, and treatment decisions must balance all of them. ILD is sometimes the presenting feature, and a rheumatology partnership is part of routine care rather than a referral of last resort.

Pulmonary hypertension and the right heart

Common in advanced fibrosis, driven by capillary destruction and hypoxic vasoconstriction, and a major determinant of exercise limitation and prognosis. Disproportionate breathlessness or desaturation relative to lung function should prompt echocardiography.

Gastro-oesophageal reflux

Highly prevalent, frequently silent, and implicated in both the pathogenesis and the progression of fibrosis through micro-aspiration — particularly in systemic sclerosis, where oesophageal dysmotility is near-universal.

Musculoskeletal and nutritional

Progressive deconditioning, sarcopenia and weight loss, compounded by corticosteroid myopathy and osteoporosis. Muscle weakness contributes substantially to exercise limitation independently of the lungs, which is precisely why it is treatable.

Mood, cough and quality of life

Anxiety, depression and social isolation are common and under-treated. Chronic cough is frequently rated by patients as the most disabling symptom, causing incontinence, exhaustion, disturbed sleep and social withdrawal, and it deserves active treatment rather than acceptance.

Lung cancer

Fibrotic ILD is an independent risk factor for lung cancer, and new nodules or a change in symptoms warrant investigation rather than attribution to the underlying disease.

Living with interstitial lung disease

Staying active

Exercise does not damage the lungs, and desaturation during supervised exercise with appropriate oxygen is not harmful. The instinct to avoid breathlessness produces deconditioning that worsens it, and reversing that belief is often the most useful conversation in the clinic.

Using oxygen well

Ambulatory oxygen enables activity that would otherwise be impossible, and portable concentrators make it practical. Many patients resist it as a marker of decline; framing it as equipment that lets them keep going is more accurate and better received.

Pacing and energy conservation

Planning the day around a limited budget, breaking tasks up, sitting where possible, and using breathing control before rather than after exertion. Practical adjustments — a shower chair, a trolley, moving the bedroom downstairs — preserve independence.

Managing cough

Reflux treatment, cough-suppression techniques, breathing control, hydration and, where refractory, medication. Cough is asked about specifically, because patients frequently do not raise it assuming nothing can be done.

Vaccination and infection avoidance

Influenza, pneumococcal, COVID-19 and RSV vaccination, prompt treatment of chest infection, and awareness that infection can precipitate an acute exacerbation.

Psychological support and planning ahead

A progressive, breathless illness carries a heavy psychological burden for patients and families. Advance care planning, discussed early and revisited, allows people to shape what happens rather than have it decided in a crisis. Transplant referral, where appropriate, is made early rather than when the person is too unwell to be a candidate.

Prognosis

The outlook varies enormously by subtype — from stable or genuinely reversible inflammatory ILD and hypersensitivity pneumonitis where the antigen is removed, to progressive fibrosis with a course resembling IPF and a median survival measured in a few years. What most reliably predicts outcome is not the label but the behaviour: the trajectory of FVC and DLCO over six to twelve months, six-minute walk distance and desaturation, the extent of fibrosis on CT, and the presence of pulmonary hypertension. Accurate subtype diagnosis, antifibrotic or immunosuppressive therapy as appropriate, oxygen and pulmonary rehabilitation all influence both survival and how the person lives in the meantime.

Role of the physiotherapist

Pulmonary rehabilitation is strongly recommended in ILD and is the intervention with the most consistent symptomatic benefit. A Cochrane review found pulmonary rehabilitation improved functional exercise capacity, breathlessness and quality of life in people with ILD, including those with IPF.⁹ An Australian randomised trial confirmed improvements in exercise capacity, symptoms and quality of life, with benefits greatest in those with less severe disease — an argument for referring early rather than when the person is already severely limited.¹⁰

Delivering it well in ILD differs from COPD. Exertional desaturation is profound and rapid, so oxygen titration during exercise is a core physiotherapy task, and training is frequently delivered with supplemental oxygen at flows well above resting requirements. Interval training is often better tolerated than continuous work. Recovery between efforts is slower. Resistance training matters disproportionately, since peripheral muscle weakness and corticosteroid myopathy limit function independently of the lungs.

Beyond rehabilitation, physiotherapy provides breathing control and pacing for breathlessness, positions of ease, fan therapy, cough-suppression techniques for the distressing dry cough, energy conservation and equipment advice, and exercise oximetry assessment that informs oxygen prescription. Because breathlessness and anxiety amplify one another, addressing the fear directly is part of the treatment. And as disease progresses, physiotherapy continues into the palliative phase, where the goal shifts from improving capacity to preserving comfort, dignity and the activities that still matter.

Part 1 · References

1. Wijsenbeek M, Cottin V. Spectrum of fibrotic lung diseases. N Engl J Med 2020;383(10):958–968.
2. Raghu G, Remy-Jardin M, Richeldi L, et al. Idiopathic pulmonary fibrosis (an update) and progressive pulmonary fibrosis in adults: an official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med 2022;205(9):e18–e47.
3. Raghu G, Remy-Jardin M, Ryerson CJ, et al. Diagnosis of hypersensitivity pneumonitis in adults: an official ATS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med 2020;202(3):e36–e69.
4. Tashkin DP, Roth MD, Clements PJ, et al. Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (Scleroderma Lung Study II): a randomised controlled, double-blind, parallel group trial. Lancet Respir Med 2016;4(9):708–719.
5. Flaherty KR, Wells AU, Cottin V, et al. Nintedanib in progressive fibrosing interstitial lung diseases (INBUILD). N Engl J Med 2019;381(18):1718–1727.
6. Distler O, Highland KB, Gahlemann M, et al. Nintedanib for systemic sclerosis-associated interstitial lung disease (SENSCIS). N Engl J Med 2019;380(26):2518–2528.
7. Waxman A, Restrepo-Jaramillo R, Thenappan T, et al. Inhaled treprostinil in pulmonary hypertension due to interstitial lung disease (INCREASE). N Engl J Med 2021;384(4):325–334.
8. Visca D, Mori L, Tsipouri V, et al. Effect of ambulatory oxygen on quality of life for patients with fibrotic lung disease (AmbOx): a prospective, open-label, mixed-method, crossover randomised controlled trial. Lancet Respir Med 2018;6(10):759–770.
9. Dowman L, Hill CJ, May A, Holland AE. Pulmonary rehabilitation for interstitial lung disease. Cochrane Database Syst Rev 2021;(2):CD006322.
10. Dowman LM, McDonald CF, Hill CJ, et al. The evidence of benefits of exercise training in interstitial lung disease: a randomised controlled trial. Thorax 2017;72(7):610–619.

References are numbered in citation order (Vancouver/BMJ style) and were current at the time of writing. Guidelines are living documents — verify against the latest version before clinical use.