Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia of unknown cause with a histological and radiological pattern of usual interstitial pneumonia (UIP), affecting older adults.

Incidence 3 to 9 per 100,000 per year; mean age at diagnosis about 65 to 70; more frequent in men and smokers.

Pathogenesis: repetitive alveolar epithelial injury in genetically susceptible, ageing lungs (telomere shortening, TERT, TERC, RTEL1, PARN; surfactant protein C, MUC5B promoter polymorphism rs35705950 in about 35%), leading to aberrant fibroblast activation and extracellular matrix deposition.

Risk factors: smoking, microaspiration/reflux, metal and wood dust, viral infection, family history (familial pulmonary fibrosis in 5 to 20%).

Median survival 3 to 5 years from diagnosis. GAP index (gender, age, physiology) stages prognosis. Acute exacerbations (annual incidence 5 to 15%) carry in hospital mortality over 50%.

Complications: pulmonary hypertension, lung cancer (risk increased 7 to 14 fold), emphysema (combined pulmonary fibrosis and emphysema), respiratory failure.

• Insidious exertional dyspnoea and nonproductive cough over more than 6 months.
• Bibasal end inspiratory crackles in nearly all, clubbing in 25 to 50%.
• Fatigue and weight loss late. Absence of systemic features of connective tissue disease.

• HRCT: UIP pattern (subpleural, basal predominant fibrosis, honeycombing with or without traction bronchiectasis) is sufficient in the right clinical context without biopsy. Absence of features inconsistent with UIP (extensive ground glass, micronodules, mosaic attenuation, cysts).
• Exclude other causes: exposure history, drugs, CTD serology, hypersensitivity pneumonitis.
• Pulmonary function: FVC and DLCO reduced; FVC decline of 5 to 10% in a year is significant; six minute walk test.
• Biopsy (cryobiopsy or surgical) only when HRCT is probable or indeterminate; multidisciplinary discussion.
• Echocardiography, polysomnography as needed. Genetic testing and telomere length in familial disease.

• Antifibrotic therapy for all eligible patients (slows decline in FVC, reduces mortality and exacerbations):
  • Nintedanib 150 mg twice daily with food (100 mg twice daily if intolerant).
  • Pirfenidone 267 mg three times daily increasing over 2 weeks to 801 mg three times daily with meals; photosensitivity, nausea, liver enzyme monitoring monthly for 3 months then every 3 months.
  • Nerandomilast (PDE4B inhibitor) is a newer option. Nintedanib and pirfenidone are not combined routinely.
• Avoid immunosuppression with prednisolone/azathioprine/N acetylcysteine (increases mortality). Long term corticosteroids not recommended.
• Treat reflux with proton pump inhibitor; antireflux surgery not routinely recommended.
• Long term oxygen therapy if PaO2 55 mmHg or less (or 60 mmHg with cor pulmonale); ambulatory oxygen for exertional desaturation.
• Pulmonary rehabilitation, vaccinations (influenza, pneumococcal, COVID 19, RSV), smoking cessation.
• Cough: low dose morphine 5 mg twice daily or nalbuphine ER; breathlessness: opioids, fans.
• Acute exacerbation: oxygen/high flow, methylprednisolone 500 to 1000 mg IV for 3 days then prednisolone taper (low evidence), antibiotics, avoid intubation unless transplant bridge.
• Lung transplantation: early referral for patients under 65 to 70 (DLCO under 40%, FVC under 50%, oxygen need).
• Palliative care early; advance care planning.