Idiopathic pulmonary fibrosis

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Idiopathic pulmonary fibrosis is the clinical diagnosis associated with a usual interstitial pneumonia pattern after known causes have been excluded. It is distinct from the broader historical term cryptogenic fibrosing alveolitis. Age, phenotype, exposure history, autoimmune evaluation and HRCT are integrated at an ILD multidisciplinary meeting. Diagnostic confidence may be high without tissue; conversely, honeycombing does not make disease idiopathic when asbestos exposure, chronic hypersensitivity pneumonitis or connective-tissue disease remains credible.

The course varies but is generally progressive. Follow trajectory through symptoms, forced vital capacity, gas transfer, exercise tolerance and oxygenation, recognising that an apparently small percentage change can be meaningful when repeated and technically sound. Acute exacerbation is a severe diffuse lung injury superimposed on fibrosis and carries poor prognosis, but it has no single confirmatory test. Infection and other reversible triggers must be actively evaluated.

Care is both antifibrotic and supportive. Specialist teams counsel on nintedanib or pirfenidone under the applicable NICE appraisal, manage toxicity, and revisit treatment when disease progresses or adverse effects dominate. Rehabilitation and anticipatory care address breathlessness, cough, fatigue, anxiety and future decisions. Jurisdictional access, transplant referral and oxygen provision vary, so the local ILD pathway remains authoritative.

Key points

IPF is a chronic progressive fibrosing interstitial pneumonia of unknown cause, usually occurring in older adults and confined to the lungs.
Typical clues are insidious exertional breathlessness, dry cough, fine basal inspiratory crackles, clubbing and a restrictive or gas-transfer defect.
The diagnosis requires exclusion of domestic, occupational, medicine and connective-tissue causes; 'idiopathic' is not established by HRCT alone.
A usual interstitial pneumonia pattern favours subpleural basal reticulation, traction bronchiectasis and honeycombing, without features suggesting an alternative diagnosis.
When clinical context and HRCT are sufficiently characteristic, surgical lung biopsy is unnecessary and may expose the patient to serious harm.
Antifibrotics slow physiological decline but do not reverse established fibrosis; benefits, adverse effects and stopping rules should be discussed honestly.
Nintedanib and pirfenidone eligibility follows current NICE technology appraisals, specialist prescribing and local commissioning arrangements.
Pulmonary rehabilitation, smoking cessation, vaccination, oxygen assessment and symptom-focused care should begin alongside disease-modifying discussion.
Serial decline, exertional desaturation and pulmonary hypertension matter prognostically even if resting saturation or spirometric volumes appear acceptable.
Lung transplantation should be considered early enough for assessment in potentially suitable patients, rather than after irreversible deconditioning or crisis.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Ageing susceptible epithelium

Age-related loss of alveolar repair capacity in a genetically susceptible person is central, despite no single identifiable initiating cause.

Genetic predisposition

Telomere-maintenance, surfactant and mucin-pathway variants increase risk in familial and some apparently sporadic disease, especially when other respiratory vulnerabilities are present.

Smoking and inhaled exposures

Tobacco smoke, metal or wood dust and other inhaled injury are associated with risk, but a credible causal exposure may indicate a non-idiopathic diagnosis.

Microaspiration and viral hypotheses

Reflux-associated microaspiration and viral injury have been proposed as repetitive epithelial stresses, without establishing a single universal cause.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Repeated epithelial injury
Susceptible alveolar epithelial cells are injured and fail to regenerate normally, with relatively limited primary inflammation.
2
Fibroblast activation
Abnormal repair signals recruit and activate fibroblasts and myofibroblasts in patchy microscopic foci, which helps produce the characteristic physiological impairment.
3
Matrix deposition
Excess collagen progressively thickens and distorts the interstitium, producing traction bronchiectasis and honeycomb cysts, contributing to the resulting loss of respiratory reserve.
4
Mechanical propagation
Stiffer fibrotic regions concentrate stress at their margins, potentially driving further epithelial injury and spatial progression.
5
Gas-exchange failure
Destroyed capillary-alveolar units and reduced compliance cause exertional desaturation, escalating work of breathing and eventually respiratory failure.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Typical chronic phenotype

An older adult develops progressive exertional breathlessness and persistent dry cough over months to years, with fine bibasal crackles and sometimes clubbing. Systemic inflammatory features are absent.

Usual interstitial pneumonia pattern

HRCT shows basal and subpleural predominant reticulation with traction bronchiectasis or bronchiolectasis and honeycombing, while marked mosaicism, profuse nodules or extensive consolidation suggests another process.

Physiological progression

Falling forced vital capacity or TLCO, worsening exertional desaturation, shorter walk distance and increasing daily limitation indicate progression after test quality and alternative causes are considered.

Acute exacerbation syndromeRed flag

New severe dyspnoea over usually less than one month with new bilateral ground-glass opacity or consolidation superimposed on UIP is life-threatening after oedema and other causes are addressed.

Pulmonary vascular complicationRed flag

Breathlessness, syncope, oedema or oxygen need disproportionate to lung volumes raises pulmonary hypertension, pulmonary embolism or cardiac disease and warrants prompt specialist evaluation.

Features arguing against idiopathic disease

Bird or mould exposure, engineered-stone or asbestos history, inflammatory joints, Raynaud phenomenon, muscle weakness, medication timing or prominent air trapping demands diagnostic reconsideration.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
High-resolution computed tomographyFirst step
Why
Determine whether the fibrosis has a UIP probability pattern.
Interpretation and limitations
Thoracic radiology should classify distribution and features, identify emphysema or malignancy and flag findings inconsistent with UIP. Technical protocol and multidisciplinary context affect confidence.
02
Spirometry, lung volumes and TLCO
Why
Measure baseline impairment and subsequent trajectory.
Interpretation and limitations
Restriction with reduced gas transfer is common, but emphysema may preserve volumes. Repeat technically comparable tests and interpret changes with symptoms rather than using a single threshold in isolation.
03
Autoimmune assessment
Why
Exclude a connective-tissue disease capable of producing UIP.
Interpretation and limitations
Clinical review determines targeted serology. Positive antibodies require phenotype-based interpretation; some systemic diseases emerge after lung presentation and warrant longitudinal review.
04
Lifetime exposure and medicine assessment
Why
Exclude alternative fibrotic causes before calling disease idiopathic.
Interpretation and limitations
Ask about birds, mould, farms, metalworking fluids, asbestos, stone dust, drugs and radiotherapy with dates and intensity. Absence of a remembered exposure is not proof of absence.
05
Standardised exercise test
Why
Quantify functional capacity and exertional oxygen desaturation.
Interpretation and limitations
Document distance, symptoms, baseline and nadir saturation, oxygen device and flow. Decline may prompt rehabilitation, oxygen or transplant discussion but is not specific for IPF.
06
Echocardiography and cause-directed acute tests
Why
Investigate disproportionate deterioration or complications.
Interpretation and limitations
Echocardiography estimates cardiac and pulmonary vascular burden but does not definitively diagnose pulmonary hypertension. Acute CT angiography, cultures or cardiac testing are selected by the presentation.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Chronic hypersensitivity pneumonitis

Bird, mould or workplace antigen exposure with mosaic air trapping or centrilobular change argues against idiopathic UIP.

Connective-tissue-disease ILD

Raynaud phenomenon, inflammatory joints, muscle or skin findings and targeted serology may reveal systemic autoimmunity despite a UIP pattern.

Asbestosis

A substantial cumulative asbestos history with pleural plaques or diffuse pleural thickening supports occupational fibrosis, with targeted examination and testing used to resolve the uncertainty.

Drug-induced fibrosis

A compatible exposure to a fibrogenic medicine or thoracic radiotherapy requires causal review before disease is called idiopathic.

Fibrotic sarcoidosis

Upper-zone peribronchovascular fibrosis, nodal disease and granulomatous extrapulmonary features favour sarcoidosis, while chronology and directed testing distinguish the competing explanation.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01DiagnosisConfirm IPF without unnecessary biopsyFirst stepChronic fibrotic ILD is suspected in an appropriate adult.

1Document clinical tempo, smoking, full medicine and exposure histories, and targeted connective-tissue findings; obtain complete physiology and protocolled HRCT.
2Present clinical and radiological evidence at an ILD multidisciplinary meeting to judge UIP pattern, credible causes and diagnostic confidence.
3If confidence remains insufficient and the answer would alter care, consider lavage or tissue only after individual procedural and exacerbation risk is discussed.
4Communicate the working diagnosis, uncertainty, likely course and contact route in plain language, with a plan to revisit unexpected features.

02Disease modificationSelect and support antifibrotic treatmentIPF is established and the patient is considering treatment.

1Check current NICE eligibility, jurisdictional commissioning, comorbidities, interactions, liver function and patient priorities before selecting nintedanib or pirfenidone.
2Explain that treatment aims to slow decline rather than improve scarring; provide medicine-specific dosing, missed-dose, adverse-effect and contraception counselling.
3Monitor clinical tolerance and laboratory safety, using food, symptom treatment, temporary interruption or dose reduction according to the current SmPC and specialist protocol.
4Review benefit and burden at agreed intervals; physiological progression alone does not prove treatment failure, while intolerable toxicity requires shared reconsideration.

03Acute deteriorationSeparate exacerbation from reversible causesA person with IPF worsens substantially over days or weeks.

1Assess airway, respiratory effort, oxygenation and haemodynamics, titrate oxygen appropriately and obtain early senior respiratory and critical-care input.
2Investigate infection, embolism, oedema, myocardial disease, pneumothorax, aspiration and medicine toxicity using cultures, imaging and cardiac tests selected to the presentation.
3Discuss likely acute exacerbation with the ILD team only after the syndrome is characterised; corticosteroid and antimicrobial practice is evidence-limited and locally governed.
4EscalationIntegrate documented preferences, reversibility and transplant status into escalation decisions, while continuing active relief of breathlessness and distress.

04Whole-person carePlan for progressive diseaseAt diagnosis and every subsequent specialist review.

1Refer for pulmonary rehabilitation, optimise vaccination and smoking cessation, assess exertional or resting oxygen needs and treat important comorbid conditions.
2Discuss transplant suitability early in eligible patients, recognising that referral criteria and age or comorbidity limits vary between centres.
3Address cough, breathlessness, fatigue, nutrition, mood, work and carer burden, involving palliative expertise alongside active respiratory treatment when useful.
4Record future-care preferences and emergency contacts before a crisis; revisit these conversations as function and priorities change.

Key medicines and prescribing safety2 treatments · regimens, roles and cautions

Antifibrotic treatment that slows decline in lung function for eligible adults with IPF under current NICE criteria.

Nintedanib

Specialist initiation is normally 150 mg orally twice daily approximately twelve hours apart with food; reduce to 100 mg twice daily, interrupt or discontinue for intolerance as directed by the current SmPC.

Check liver function before and during treatment. Diarrhoea and nausea are common; dehydration, bleeding, arterial thromboembolism and gastrointestinal perforation risks require context. Avoid in pregnancy and review anticoagulants, hepatic impairment and interacting medicines.

Antifibrotic option that slows functional decline for adults meeting the applicable NICE and specialist eligibility arrangements.

Pirfenidone

Specialist-supervised titration over fourteen days: 267 mg three times daily for days 1–7, 534 mg three times daily for days 8–14, then 801 mg three times daily with food, subject to current product instructions.

Obtain liver tests before treatment, monthly for six months and then every three months unless more frequent review is indicated. Counsel on nausea, anorexia, photosensitivity, sun protection, smoking-related reduced exposure and important CYP1A2 interactions.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Acute exacerbation

New diffuse alveolar injury superimposed on fibrosis causes rapid severe hypoxaemia after infection, embolism, oedema and other triggers are assessed.

Pulmonary hypertension

Vascular destruction, hypoxic vasoconstriction and remodelling increase pulmonary resistance, worsening breathlessness and prognosis, and increasing the burden of otherwise local respiratory disease.

Respiratory failure

Progressive loss of compliant gas-exchange surface leads to exertional then resting hypoxaemia and escalating oxygen need.

Lung cancer

Older age, smoking and fibrotic epithelial injury increase malignancy risk, while tumours may be difficult to distinguish within distorted lung.

Frailty and symptom burden

Breathlessness, cough, fatigue and inactivity drive deconditioning, weight loss, anxiety and loss of independence, adding morbidity beyond the initial pulmonary disorder.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Review symptoms, daily activity, weight, cough, treatment goals and resting oxygen saturation at each ILD appointment.
Repeat forced vital capacity and TLCO commonly every three to six months, adjusting frequency to stability and local service protocol.
Monitor exertional desaturation with a reproducible walk test when function changes and reassess ambulatory oxygen through the commissioned pathway.
For nintedanib or pirfenidone, follow medicine-specific liver testing, adverse-effect enquiry, interaction review and specialist dose-modification rules.
Look for pulmonary hypertension, lung cancer, infection, reflux, sleep disturbance, anxiety and depression when decline or symptom burden is disproportionate.
Revisit rehabilitation, transplant eligibility, palliative input and advance care preferences as the disease trajectory becomes clearer.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

UIP does not equal IPF

UIP is also seen with rheumatoid arthritis, chronic exposure-related disease and asbestosis. The word idiopathic belongs only after those alternatives have been evaluated.

Antifibrotics preserve rather than restore

A patient may continue to worsen while receiving effective therapy because the expected benefit is slower average decline, not reversal of fibrosis or guaranteed stability.

Emphysema hides restriction

Coexistent emphysema can keep forced vital capacity near normal while TLCO, pulmonary vascular burden and exertional oxygenation deteriorate substantially.

Biopsy can worsen disease

Surgical sampling is not a routine proof step. In a sufficiently characteristic clinical and radiological presentation it adds risk without improving the decision.

Supportive care is active treatment

Rehabilitation, oxygen assessment, cough and breathlessness management, carer support and advance planning address outcomes that matter even when fibrosis cannot be reversed.

11Common pitfallsFrequent interpretation and management errors.

01
Diagnosing IPF from age and honeycombing without a credible exposure, medicine and autoimmune assessment.
02
Promising that an antifibrotic will improve breathlessness or regenerate scarred lung.
03
Continuing a full antifibrotic dose through severe diarrhoea, weight loss or liver injury without contacting the specialist team.
04
Calling every acute respiratory decline an IPF exacerbation before excluding infection, embolism, oedema and pneumothorax.
05
Waiting for resting hypoxaemia before asking about exertional desaturation and activity limitation.
06
Leaving transplant and future-care conversations until a crisis removes realistic choices.