What is the diagnostic approach for hypersensitivity pneumonitis?

Diagnostic Approach for Hypersensitivity Pneumonitis

Diagnose hypersensitivity pneumonitis using a systematic multidisciplinary approach that integrates detailed exposure history, high-resolution CT patterns, bronchoalveolar lavage lymphocyte analysis, and when necessary, lung biopsy—with the critical first step being identification of the inciting antigen through comprehensive environmental and occupational exposure assessment. 1

Initial Clinical Assessment

Exposure History (Highest Priority)

• Obtain a thorough environmental and occupational exposure history focused on establishing the type, extent, and temporal relationship between exposure(s) and respiratory symptoms using a comprehensive questionnaire tailored to your geographic region. 1, 2
• Specifically inquire about: bird exposure (including feathers in bedding), mold exposure, hot tubs, humidifiers, agricultural work, and occupational exposures that temporally parallel disease onset. 2, 3
• Include an occupational medicine specialist and environmental hygienist if the exposure source is obscure or occupational exposure is suspected. 1, 2
• Recognize that the inciting antigen remains unidentified in up to 60% of cases despite thorough history, which is independently associated with worse survival (HR 2.08). 2, 3

Clinical Phenotype Classification

Classify patients into nonfibrotic versus fibrotic HP phenotypes, as this determines the diagnostic algorithm and has major prognostic implications. 1

High-Resolution CT Imaging

Perform HRCT in all patients with suspected HP as a critical diagnostic component. 2

Key HRCT Findings

• Nonfibrotic HP: Bilateral mosaic attenuation pattern (air trapping on expiration), ground-glass opacities in middle and lower lung zones, ill-defined centrilobular nodules. 2, 4
• Fibrotic HP: Small airways abnormalities with fibrosis, mosaic attenuation, upper/mid-lung predominance (distinguishing it from the basal-predominant honeycombing of IPF). 3

Laboratory Testing

Serum IgG Testing

Perform serum antigen-specific IgG testing against potential antigens associated with HP to help identify exposures, though interpret results cautiously given variable sensitivity (25-96%) and specificity (60-100%). 1, 2

Bronchoalveolar Lavage

For Nonfibrotic HP

Obtain BAL fluid for lymphocyte cellular analysis (strong recommendation). 1

• BAL lymphocytosis >30% strongly suggests HP. 3
• Look for increased total cell count with T lymphocyte predominance (>50%), increased neutrophils (>3%), and increased mast cells (>1%). 4

For Fibrotic HP

Obtain BAL for lymphocyte cellular analysis before considering more invasive procedures, though recognize that sensitivity decreases in established fibrosis. 1, 2, 3

Lung Biopsy (When Diagnosis Remains Uncertain)

For Nonfibrotic HP

• Perform transbronchial forceps lung biopsy when other diagnostic tests are inconclusive. 1, 2
• Reserve surgical lung biopsy only when all other diagnostic testing has not yielded a diagnosis. 1, 2

For Fibrotic HP

• Consider transbronchial lung cryobiopsy or surgical lung biopsy if diagnosis remains uncertain after initial workup. 3
• Look for ill-defined non-necrotizing granulomas, cellular interstitial pneumonia, cellular bronchiolitis, and epithelioid cell granulomas. 5, 4
• Recognize that fibrotic HP demonstrates a broader pathologic spectrum including UIP pattern, NSIP pattern, organizing pneumonia, and airway-centric fibrosis. 3

Diagnostic Criteria Integration

Base the diagnosis on a combination of compatible HRCT findings, BAL lymphocytosis, and compatible histopathological findings when biopsy is performed, integrated through multidisciplinary discussion. 2, 5

Critical Pitfalls to Avoid

• Do not exclude HP based on an unrevealing exposure history alone—continue the exposure assessment process until diagnosis is more certain. 1
• Do not delay antigen identification efforts—unidentified antigen exposure is associated with shortened survival (HR 1.76-2.08). 3
• Do not assume clinical improvement with antigen avoidance confirms the diagnosis—disease may progress despite apparent remediation, suggesting other contributing exposures or factors. 1
• Do not confuse fibrotic HP with IPF—look for small airways abnormalities, mosaic attenuation, and upper/mid-lung predominance rather than basal honeycombing. 3

Diagnostic Confidence Levels

Establish diagnostic confidence (definite, probable, or possible HP) prior to considering invasive procedures, using the integrated assessment of exposure history, CT pattern, BAL results, and when available, histopathology. 1