What is the diagnostic workup for chronic hypersensitivity pneumonitis?

Diagnostic Workup for Chronic Hypersensitivity Pneumonitis

The diagnostic workup for chronic hypersensitivity pneumonitis (HP) requires a multidisciplinary assessment that incorporates a thorough environmental and occupational exposure history, high-resolution CT (HRCT) imaging, bronchoalveolar lavage (BAL), and in some cases, lung biopsy to establish diagnostic confidence. 1

Initial Evaluation

• A detailed environmental and occupational exposure history focused on establishing the type, extent, and temporal relationship of exposure(s) to symptoms is essential, ideally using a comprehensive questionnaire tailored to the geographic region 1
• If an occupational exposure is suspected, consider including an occupational medicine specialist and environmental hygienist in the diagnostic workup 1
• Clinical improvement after complete antigen avoidance can support the diagnosis, though lack of improvement does not rule out HP 1

Imaging Studies

• HRCT is a critical component of the diagnostic workup and should be performed in all patients with suspected HP 1
• Key HRCT findings in chronic HP include:
  • Mosaic attenuation pattern (air trapping) 1
  • Upper lobe-predominant fibrosis (unlike IPF) 2
  • Ground-glass opacities with peripheral reticulation 3
  • Fibrotic changes with architectural distortion 1

Laboratory Testing

• Serum antigen-specific IgG testing against potential antigens associated with HP is suggested, though results must be interpreted cautiously 1
• Limitations of serum testing include:
  • Lack of standardized antigen preparations for most inciting agents
  • Variable diagnostic cutoff thresholds
  • Limited validation in diverse populations
  • Sensitivity ranging from 25% to 96% and specificity from 60% to 100% 1
• A positive test may suggest a putative exposure but should not be used alone for diagnosis 1

Bronchoalveolar Lavage (BAL)

• BAL is recommended for lymphocyte cellular analysis in both nonfibrotic and fibrotic HP 1
• Lymphocytosis in BAL fluid (typically CD8+ T cells) strongly supports the diagnosis of HP 4
• BAL should be performed before considering more invasive procedures like lung biopsy 1

Lung Biopsy

For nonfibrotic HP:

• Transbronchial forceps lung biopsy is suggested when other diagnostic tests are inconclusive 1
• Surgical lung biopsy should only be considered when all other diagnostic testing has not yielded a diagnosis 1

For fibrotic HP:

• Transbronchial lung cryobiopsy is suggested when less invasive testing is inconclusive 1
• Surgical lung biopsy may be necessary in cases where the diagnosis remains uncertain 1

Histopathological Features

• Key histopathological findings in chronic HP include:
  • Poorly formed non-necrotizing granulomas or isolated giant cells 3, 5
  • Peribronchiolar fibrosis ("bridging fibrosis") 2
  • Three patterns of fibrosis may be seen:
    • Peripheral fibrosis resembling usual interstitial pneumonia (UIP)
    • Homogeneous linear fibrosis resembling nonspecific interstitial pneumonia (NSIP)
    • Irregular predominantly peribronchiolar fibrosis 3

Diagnostic Criteria

The diagnosis of HP should be based on a combination of:

• Identification of a causative antigen (when possible) 5
• Compatible HRCT findings 1
• BAL lymphocytosis 1, 4
• Compatible histopathological findings when biopsy is performed 1
• Temporal relationship between exposure and disease 5

Common Pitfalls and Caveats

• Chronic HP is frequently misdiagnosed as idiopathic pulmonary fibrosis (IPF) or fibrotic nonspecific interstitial pneumonia 2
• The inciting antigen is not identified in up to 60% of patients despite a thorough history 1
• Serum precipitins have variable sensitivity and specificity and should not be relied upon as the sole diagnostic test 1
• Histopathological findings in chronic HP may closely mimic UIP or fibrotic NSIP, making accurate diagnosis challenging 3
• Accurate diagnosis often requires consultation among clinicians, radiologists, and pathologists in a multidisciplinary discussion 2

Distinguishing chronic HP from other interstitial lung diseases is crucial as treatment approaches differ significantly, with HP typically managed with immunosuppressive agents and antigen avoidance rather than antifibrotic agents used for IPF 2.