What tests confirm hypersensitivity pneumonitis?

Diagnostic Testing to Confirm Hypersensitivity Pneumonitis

The diagnosis of HP requires integration of three key elements: documented exposure to an inciting agent, characteristic HRCT findings, and BAL lymphocytosis (≥30%), with the combination of all three providing high diagnostic confidence. 1

Core Diagnostic Algorithm

Step 1: Exposure Assessment

• Obtain a thorough exposure history focusing on occupational, household, and recreational exposures to known HP antigens (bacteria, fungi, avian proteins, chemicals, metals) 1, 2
• Consider serum IgG testing against suspected antigens, though this cannot be used alone to confirm or exclude HP due to lack of standardization and variable sensitivity/specificity 1
• Serum IgG may help identify putative exposures when history is unclear (e.g., musty odor without visible mold), but positive results only suggest exposure, not disease 1

Step 2: High-Resolution CT Imaging

• HRCT is essential and should be performed using standardized technique and reviewed with a thoracic radiologist 1
• Characteristic findings include:
  • Profuse centrilobular nodules of ground-glass attenuation 1, 3, 4
  • Inspiratory mosaic attenuation with air-trapping 1
  • Three-density sign 1
• HRCT findings alone cannot make a definitive diagnosis and must be integrated with clinical context 1
• In chronic/fibrotic HP, look for reticulation, traction bronchiectasis, and honeycombing 5, 6

Step 3: Bronchoalveolar Lavage (BAL)

For Nonfibrotic HP:

• BAL with lymphocyte cellular analysis is recommended (stronger recommendation than for fibrotic HP) 1
• A lymphocyte threshold of ≥30% is considered reasonable (normal is 10-15% in nonsmokers) 1
• BAL also helps exclude pulmonary infections, particularly M. tuberculosis in endemic areas 1

For Fibrotic HP:

• BAL is suggested but with weaker recommendation due to less consistent lymphocytosis in fibrotic disease 1
• Lymphocytosis ≥40% may help exclude IPF and increase diagnostic confidence when exposure and HRCT are compatible 1

Step 4: High-Confidence Diagnosis Criteria

A high-confidence diagnosis can be made when ALL three are present: 1

1. Identified exposure to known HP antigen
2. Typical HP pattern on HRCT
3. BAL lymphocytosis (≥30%)

When this triad is present, additional testing is NOT routinely needed 1

When Additional Testing Is Required

Transbronchial Biopsy

• Suggested for nonfibrotic HP when the diagnostic triad is incomplete 1
• Look for suppressor cytotoxic lymphocytosis and granulomatous alveolitis 7
• Transbronchial lung cryobiopsy (TBLC) may be considered in nonfibrotic HP depending on local expertise 1

Surgical Lung Biopsy (SLB)

• Reserved for cases where all other testing has not yielded a diagnosis 1
• Should be preceded by multidisciplinary discussion 1
• Infrequently needed in nonfibrotic HP 1
• Consider in fibrotic HP when diagnosis remains uncertain and results would alter management 1

Critical Pitfalls to Avoid

• Do not rely solely on serum IgG testing - lack of standardization, variable cutoffs, and limited validation make this insufficient for diagnosis 1
• Do not perform antigen-specific inhalation challenge - lack of standardized techniques and validated criteria, plus limited availability 1
• Do not use HRCT findings in isolation - must integrate with clinical context and exposure history 1
• In patients with high pretest probability (compelling exposure + typical HRCT), BAL may not significantly alter post-test probability and can be omitted 1
• Recognize that BAL lymphocytosis is less sensitive in fibrotic HP - absence does not exclude the diagnosis 1
• No single threshold of BAL lymphocytes definitively distinguishes HP from other ILDs - the area under the curve is poor (0.44-0.71) across various comparisons 1

Role of Multidisciplinary Discussion

When diagnostic confidence is not high after initial testing, multidisciplinary discussion is essential to determine need for additional invasive procedures and integrate all available data 1