Key Facts

Hypersensitivity pneumonitis (HP) is an immune-mediated inflammatory and/or fibrotic lung disease caused by repeated inhalation of specific organic or chemical antigens in sensitised individuals. It was previously known as extrinsic allergic alveolitis (EAA).

Epidemiology

• Prevalence varies by region and occupation
• Farmer's lung: ~2-9% of exposed farmers develop HP
• Bird fancier's lung: ~5-15% of exposed individuals
• Accounts for ~5-15% of cases referred to ILD clinics
• Chronic fibrotic HP is increasingly recognised as a significant cause of progressive pulmonary fibrosis

Aetiology

Pathophysiology

• Type III hypersensitivity: immune complex deposition → complement activation → neutrophilic inflammation (acute)
• Type IV hypersensitivity: T-cell-mediated granulomatous inflammation (chronic)
• Non-caseating granulomas in lung parenchyma
• Chronic exposure → fibrosis (resembling UIP or NSIP pattern)
• Only ~5-15% of exposed individuals develop HP — host susceptibility factors important

Acute HP

• 4-8 hours after high-intensity antigen exposure
• Flu-like illness: fever, malaise, myalgia
• Dry cough, breathlessness
• Bibasal crackles
• Resolves within 24-48 hours of antigen removal

Subacute HP

• Weeks to months of low-level exposure
• Progressive cough and breathlessness
• Weight loss, fatigue
• May develop between acute episodes

Chronic Non-Fibrotic HP

• Progressive breathlessness and cough
• Ongoing exposure may be occult (feather duvets, mould)
• Ground-glass opacity and air trapping on CT

Chronic Fibrotic HP

• Insidious onset, mimics IPF
• Progressive dyspnoea, dry cough
• Bibasal crackles, clubbing
• Often diagnosed after antigen removed (but fibrosis progresses)

Red Flags

• Progressive fibrosis despite antigen avoidance
• Rapid FVC decline
• Mimicking IPF — may be misdiagnosed
• Occupational exposure not identified (hidden antigens)

Bedside

• Detailed exposure history: occupational, hobbies (birds, hot tubs), home environment (mould, feather bedding)
• Pulse oximetry: resting and exercise

Bloods

• Serum-specific IgG (precipitins): avian, farmer's lung panel, Aspergillus — supports exposure but not diagnostic (positive in 40-50% of asymptomatic exposed individuals)
• FBC: lymphopenia (chronic), mild eosinophilia
• CRP/ESR: mildly elevated
• Autoimmune screen: exclude CTD-ILD

Imaging

• HRCT:
  • Non-fibrotic: diffuse ground-glass opacity, centrilobular nodules, mosaic attenuation (air trapping on expiratory images)
  • Fibrotic: reticulation, traction bronchiectasis, honeycombing; upper/mid zone predominance (unlike IPF which is basal)

Special Tests

• Pulmonary function tests: restrictive pattern (reduced FVC, TLC); reduced TLCO; may have mixed pattern with air trapping
• BAL: lymphocytosis >30% (supports HP diagnosis; CD8+ predominance in some)
• Transbronchial or surgical lung biopsy: non-caseating granulomas, lymphocytic interstitial inflammation, bronchiolocentric distribution; may show fibrosis
• Antigen challenge testing: rarely used; provocation in specialist centre
• MDT discussion: essential for definitive diagnosis (clinical, radiological, pathological correlation)

Non-pharmacological

• Antigen avoidance: single most important intervention
  • Occupational: change of role, improved ventilation, respiratory protective equipment
  • Domestic: remove birds, change bedding (non-feather), mould remediation
• Report occupational HP: RIDDOR notification, HSE
• Smoking cessation

Pharmacological

Acute/subacute HP:

• Prednisolone 0.5mg/kg/day (typically 30-40mg/day) for 4-6 weeks, then taper over 3-6 months
• Only if significant symptoms/physiological impairment after antigen removal

Chronic fibrotic HP:

• Corticosteroids: limited evidence; trial may be warranted
• Mycophenolate mofetil 500mg-1g BD: steroid-sparing immunosuppression (used off-label)
• Anti-fibrotic therapy: nintedanib now approved for progressive fibrosing ILDs (including fibrotic HP) — INBUILD trial; NICE TA747
• Pirfenidone: not yet licensed for non-IPF fibrosis but under study

Surgical/Interventional

• Lung transplantation: for end-stage fibrotic HP
• Surgical lung biopsy if diagnosis uncertain

Referral Criteria

• All suspected HP: ILD specialist referral for MDT diagnosis
• Occupational HP: occupational lung disease specialist
• Industrial Injuries Disablement Benefit application for farmer's lung and other prescribed diseases
• Transplant assessment for progressive fibrotic disease

• Acute HP: excellent prognosis with antigen avoidance; complete resolution expected
• Subacute HP: good prognosis if antigen identified and removed early
• Chronic non-fibrotic HP: usually stabilises or improves with antigen avoidance
• Chronic fibrotic HP: progressive despite antigen avoidance; prognosis similar to or slightly better than IPF
• Median survival of fibrotic HP: ~5-8 years (better than IPF ~3-5 years)
• Poor prognostic factors: older age, UIP-like pattern, honeycombing, continued antigen exposure, low FVC/TLCO
• Anti-fibrotic therapy (nintedanib) slows progression in fibrotic HP

Common Causes of HP

HP Classification (2020 ATS/JRS/ALAT)