Key Facts

Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause, occurring primarily in older adults, limited to the lungs, and characterised by the histopathological and/or radiological pattern of usual interstitial pneumonia (UIP).

Epidemiology

• Incidence: ~5-10 per 100,000 per year in the UK (increasing)
• Prevalence: ~30-50 per 100,000
• Male predominance (~1.5-2:1)
• Mean age at diagnosis: 65-70 years (rare <50)
• ~5,000 new cases per year in the UK
• ~5,000 deaths per year in the UK

Aetiology

• By definition, idiopathic (unknown cause)
• Risk factors: smoking (strongest modifiable risk factor; 70% are current/ex-smokers), male sex, older age, genetic factors (MUC5B promoter variant, telomerase mutations), environmental exposures (metal/wood dust), GORD, viral infections (EBV, CMV)
• Familial IPF in ~5% (autosomal dominant with variable penetrance)

Pathophysiology

• Aberrant wound healing response in genetically susceptible individuals
• Repetitive alveolar epithelial injury → abnormal fibroblast/myofibroblast activation → excessive collagen deposition
• Progressive replacement of normal lung with fibrotic tissue
• Loss of alveolar surface area → gas exchange impairment
• UIP pattern: spatial and temporal heterogeneity — areas of fibrosis adjacent to normal lung; fibroblastic foci represent active fibrosis

Typical Presentation

• Progressive exertional breathlessness (over months to years)
• Chronic dry cough
• Fatigue
• Typically >60 years, male, ex-smoker

Clinical Signs

• Bibasal fine end-inspiratory ("Velcro") crackles — present in >90%
• Finger clubbing (~50%)
• Cyanosis (advanced disease)
• Signs of pulmonary hypertension and cor pulmonale (late)

Acute Exacerbation of IPF

• Rapid deterioration over days to weeks
• New bilateral ground-glass opacity on CT (superimposed on UIP)
• No identifiable cause (infection, PE, heart failure excluded)
• Mortality >50%

Red Flags

• Rapidly progressive breathlessness (acute exacerbation or alternative diagnosis)
• SpO₂ desaturation on exercise (significant gas exchange impairment)
• FVC decline >10% per year (poor prognosis)
• New symptoms suggesting lung cancer (5-10% of IPF patients develop lung cancer)

Bedside

• Pulse oximetry: resting and exercise (6MWT desaturation)
• Auscultation: bibasal fine inspiratory crackles

Bloods

• Autoimmune screen: ANA, RF, anti-CCP, CK, myositis-specific antibodies (exclude CTD-ILD)
• FBC: polycythaemia (chronic hypoxia)
• CRP/ESR: usually normal in IPF (if elevated, consider alternative)
• KL-6: elevated in IPF (emerging biomarker)
• BNP: if pulmonary hypertension suspected

Imaging

• HRCT chest: gold standard for diagnosis
  • Definite UIP pattern: honeycombing (subpleural, basal predominant), traction bronchiectasis, reticulation, minimal/no ground-glass opacity
  • Probable UIP: above features without honeycombing
  • Indeterminate: features not typical of UIP
  • Alternative diagnosis: features suggesting other ILD

Special Tests

• Pulmonary function tests: restrictive pattern (reduced FVC, reduced TLC), reduced TLCO (earliest and most sensitive marker), preserved or increased FEV₁/FVC ratio
• 6-minute walk test: distance and desaturation (prognostic)
• Surgical lung biopsy: only if HRCT pattern is indeterminate/alternative and diagnosis would change management; shows UIP pattern (temporal and spatial heterogeneity, fibroblastic foci, honeycombing)
• Bronchoalveolar lavage: may help exclude other causes (eosinophilia, lymphocytosis suggesting alternative diagnosis)
• MDT discussion: essential for diagnosis (respiratory physician, radiologist, histopathologist)

Non-pharmacological

• Pulmonary rehabilitation: improves exercise capacity and quality of life
• Supplemental oxygen: LTOT if PaO₂ ≤7.3 kPa; ambulatory oxygen if exercise desaturation
• Smoking cessation: essential
• Flu and pneumococcal vaccination
• Palliative care: early referral for symptom management (breathlessness, cough, anxiety)
• Psychological support: high rates of anxiety and depression

Pharmacological

Anti-fibrotic therapy (NICE NG228):

• Pirfenidone 267mg increasing to 801mg TDS (with food)

  • CAPACITY and ASCEND trials: reduces FVC decline by ~50%
  • Side effects: nausea, photosensitivity, rash, liver toxicity
  • Monitor LFTs monthly for 6 months then 3-monthly
  • NICE TA504

• Nintedanib 150mg BD

  • INPULSIS trial: reduces FVC decline by ~50%
  • Side effects: diarrhoea (most common), nausea, liver toxicity
  • Monitor LFTs
  • NICE TA379

Eligibility (NICE): FVC 50-80% predicted; discontinue if FVC decline >10% in any 12-month period

NOT recommended: immunosuppression (prednisolone + azathioprine + NAC harmful in IPF — PANTHER-IPF trial showed increased mortality)

Acute exacerbation:

• High-dose corticosteroids (methylprednisolone 1g IV for 3 days, then prednisolone taper) — limited evidence
• Broad-spectrum antibiotics to cover infection
• Supportive care; ICU if appropriate
• Mortality >50%

Surgical/Interventional

• Lung transplantation: only curative option
  • Refer early: when FVC <80% or TLCO <40%, or significant decline
  • Single or bilateral lung transplant
  • Age usually <65-70 years
• Anti-reflux surgery: debated; GORD may contribute to disease progression

Referral Criteria

• All suspected IPF: refer to specialist ILD centre for MDT diagnosis
• Transplant assessment early (when FVC <80% or TLCO <40%)
• Palliative care referral at diagnosis for advance care planning
• Clinical trial consideration

• Median survival: 3-5 years from diagnosis (variable — some stable, some rapid decline)
• Predictors of poor prognosis: low FVC (<50%), low TLCO (<40%), desaturation on 6MWT, honeycombing extent, male sex, older age
• FVC decline >10% in 6-12 months predicts mortality
• Anti-fibrotic therapy slows decline but does not reverse disease
• Acute exacerbation mortality: >50%
• Lung transplant: median survival post-transplant ~5-6 years
• Lung cancer risk: 5-10 fold increased
• GAP index (Gender, Age, Physiology) predicts mortality: Stage I ~6% 1-year mortality, Stage III ~39% 1-year mortality

GAP Index (Mortality Predictor)

UIP Pattern on HRCT