Lung Fibrosis (IPF) — Causes, HRCT Diagnosis, Nintedanib & Pirfenidone Treatment — Symptoms, Causes & Treatment | MyMedicPlus

Pulmonary fibrosis refers to a group of interstitial lung diseases (ILDs) characterised by progressive fibrotic scarring of the lung parenchyma, leading to distortion of alveolar architecture, impaired gas exchange, and progressive respiratory failure. The most common and most severe form is idiopathic pulmonary fibrosis (IPF) — a specific chronic, progressive, fibrosing interstitial pneumonia of unknown cause occurring predominantly in older adults with a usual interstitial pneumonia (UIP) histological pattern. IPF affects approximately 3 million people globally, with incidence of 2–9 per 100,000 per year increasing with age. It is more common in men and in those over 60 years. Median survival from diagnosis is 3–5 years — poorer than many cancers — though the disease course is highly variable. Antifibrotic therapies (nintedanib and pirfenidone) slow disease progression by approximately 50%, and lung transplantation remains the only curative option.

The term 'idiopathic' in IPF reflects that no single causative agent is identified, though multiple genetic and environmental risk factors have been established. Cigarette smoking: the strongest environmental risk factor — present in 70% of IPF patients (odds ratio 1.6–2.9). Occupational exposures: silica dust (stonemasons, quarrying, sandblasting), asbestos (construction, shipyard workers), metal dusts (brass, lead, steel), wood dust, textile dust, and farming (organic dusts). Gastro-oesophageal reflux disease (GERD) — chronic aspiration of gastric acid may trigger repetitive microinjury in susceptible individuals. Age over 60 and male sex. Genetic factors: familial IPF (accounts for 3–5% of cases); telomere length genes (TERT, TERC, RTEL1, PARN) — short telomeres increase IPF risk; MUC5B promoter variant rs35705950 — the strongest genetic risk factor (present in 34–38% of IPF patients versus 9–11% controls). Viral infections (EBV, CMV, HCV) have been implicated but not definitively proven. Non-IPF pulmonary fibrosis causes: connective tissue diseases (rheumatoid arthritis, systemic sclerosis — scleroderma, polymyositis, Sjogren's syndrome — CTD-ILD); hypersensitivity pneumonitis (bird-fancier's lung, farmer's lung — from organic antigens); drug-induced (methotrexate, amiodarone, nitrofurantoin, immunotherapy agents); sarcoidosis.

Progressive exertional breathlessness (dyspnoea on exertion — the dominant symptom): initially only on significant exertion, but worsening to breathlessness at rest over months to years. Dry, persistent, non-productive cough: typically refractory to antitussives. Bilateral basal 'Velcro crackles' on auscultation (fine end-inspiratory crackles — sounding like Velcro being pulled apart) — highly characteristic of UIP pattern; present in 80–90% of IPF patients. Clubbing (finger and toe nail clubbing — loss of normal nail bed angle) in approximately 25–50% of patients. Fatigue and reduced exercise tolerance. Advanced disease: cyanosis, peripheral oedema (cor pulmonale from pulmonary hypertension), signs of severe hypoxaemia. Acute exacerbation of IPF (AE-IPF): sudden, unexplained worsening of breathlessness (over 30 days), new bilateral pulmonary infiltrates on CT, and exclusion of infection, heart failure, or PE — high mortality (>50%).

High-resolution CT (HRCT) of the chest is the cornerstone of IPF diagnosis: UIP pattern features — subpleural, bibasal honeycombing with or without peripheral traction bronchiectasis/bronchiolectasis; absence of features suggesting an alternative diagnosis. Typical UIP on HRCT in appropriate clinical context negates the need for surgical lung biopsy. Pulmonary function tests (PFTs): restrictive pattern (reduced TLC, FVC, and DLCO — diffusion capacity for carbon monoxide); FVC decline of above 10% over 12 months predicts mortality. 6-minute walk test (6MWT): assesses functional capacity and predicts prognosis. Bronchoalveolar lavage (BAL): not diagnostic for IPF but helps exclude infection, malignancy, or other ILD subtypes (marked lymphocytosis suggests HP or sarcoidosis). Surgical lung biopsy (video-assisted thoracoscopic surgery — VATS): provides histological UIP confirmation when HRCT is inconclusive; requires multidisciplinary team (MDT) discussion with pulmonologist, radiologist, and histopathologist (ILD-MDT). Serology: ANA, RF, anti-CCP, anti-Scl70, anti-Ro/La, anti-Jo-1, myositis panel — to exclude CTD-ILD. Exclude hypersensitivity pneumonitis: avian precipitins, detailed occupational and domestic exposure history, BAL lymphocyte count.

Antifibrotic therapy: nintedanib (Ofev) 150 mg twice daily — tyrosine kinase inhibitor (blocking PDGFR, FGFR, VEGFR and downstream fibrotic signalling); reduces annual FVC decline by approximately 50% (INPULSIS trials); also approved for systemic sclerosis-associated ILD and other progressive fibrosing ILDs. Pirfenidone (Esbriet) 801 mg three times daily — anti-fibrotic and anti-inflammatory mechanism; reduces annual FVC decline by approximately 50% (CAPACITY/ASCEND trials). Both are first-line antifibrotic agents — choice based on tolerability and comorbidities (nintedanib: diarrhoea, nausea; pirfenidone: GI side effects, photosensitivity, hepatotoxicity). N-acetylcysteine monotherapy has no benefit (PANTHER-IPF trial). Gastroesophageal reflux treatment with PPI or H2 blocker — reduces aspiration microinjury. Pulmonary rehabilitation: improves exercise capacity and quality of life. Supplemental oxygen: for exercise-induced or resting hypoxaemia (SpO2 below 88% on air). Lung transplantation: the only treatment modifying long-term prognosis in eligible patients (bilateral lung transplant preferred; 5-year survival approximately 50–60%); refer early as waiting times are prolonged. Acute exacerbation: high-dose IV methylprednisolone (500–1000 mg/day for 3 days); broad-spectrum antibiotics; supportive care; ICU if required. Palliative care: morphine for breathlessness; symptom management and advance care planning.

Idiopathic pulmonary fibrosis (IPF) and other forms of pulmonary fibrosis carry severe and progressive complications. Respiratory failure — the primary cause of death — develops as progressive fibrosis reduces functioning alveolar surface area, causing progressive hypoxaemia (PaO2 below 8 kPa at rest), hypercapnia in end-stage disease, and ventilatory failure; supplemental oxygen becomes essential for daily activities and eventually at rest. Acute exacerbations of IPF (AE-IPF) — sudden unexplained accelerated worsening of dyspnoea with new bilateral ground-glass opacities on CT, occurring in 5-10% annually — carry 70-90% in-hospital mortality even with corticosteroids and supportive care; they are the most common cause of death in IPF. Pulmonary hypertension (PH) complicates approximately 30-50% of patients with advanced IPF — right ventricular pressure overload from progressive pulmonary vascular obliteration causes right heart failure (cor pulmonale), further worsening exercise tolerance and oxygen saturation. Lung cancer risk is increased 4-8 fold in IPF patients — particularly peripheral adenocarcinoma arising in fibrotic areas; annual CT screening is recommended. Gastro-oesophageal reflux disease (GERD) is highly prevalent in IPF (80%) — aspiration of gastric acid may accelerate fibrotic progression. Pneumothorax from rupture of subpleural fibrotic blebs requires intercostal drain insertion. Secondary polycythaemia from chronic hypoxaemia increases thrombosis risk. Severe exercise limitation, social isolation, depression (affecting 30-50% of IPF patients), and loss of independence markedly reduce quality of life in progressive disease.

Smoking cessation is the single most important modifiable prevention measure and is strongly recommended regardless of disease stage — smoking significantly accelerates IPF progression. Occupational risk reduction: wear appropriate respiratory protective equipment when working with silica, asbestos, wood, or metal dusts; use local exhaust ventilation; ensure workplace compliance with occupational health standards. GERD management: treat reflux disease aggressively (PPI or H2 antagonists) in IPF patients. Pneumococcal and annual influenza vaccination: prevent respiratory infections that can trigger acute exacerbations. Bird exposure: remove all birds and bird-related products from the home — avian antigens are a major cause of hypersensitivity pneumonitis (bird-fancier's lung), which can be mistaken for IPF; avoiding the antigen can improve HP prognosis significantly. For established IPF: avoid air travel without supplemental oxygen assessment (hypobaria at altitude may worsen hypoxaemia); avoid aspirin and NSAIDs (GI side effects that worsen antifibrotic tolerability); maintain regular ILD clinic follow-up with 6-monthly PFTs and CT reassessment.

Seek urgent assessment if you have progressive breathlessness with a dry cough, particularly if you are over 60, have a history of smoking, or work in a high-risk dusty environment — early referral to a specialist ILD clinic is essential. 'Velcro crackles' heard on chest examination are a strong indication for HRCT referral. Seek emergency treatment immediately for: sudden worsening of breathlessness over days (acute exacerbation of IPF — high mortality); SpO2 below 88% at rest; haemoptysis; fever with worsening breathlessness (infection or pneumonia). Established IPF patients should contact their ILD team promptly for any significant deterioration — antifibrotic dose adjustments, oxygen prescriptions, or hospital admission may be needed. All IPF patients should be discussed and managed at a multidisciplinary ILD team meeting and have advance care planning discussions initiated early.