What lab values are indicative of acute hypersensitivity pneumonitis in a patient?

Laboratory Values Indicative of Acute Hypersensitivity Pneumonitis

The most important laboratory finding in acute hypersensitivity pneumonitis is BAL lymphocytosis ≥30%, which serves as a key diagnostic criterion when combined with exposure history and imaging findings. 1, 2

Bronchoalveolar Lavage (BAL) Findings

Lymphocyte Count

• BAL lymphocytosis ≥30% is the recommended diagnostic threshold for supporting the diagnosis of HP across all major guidelines 1, 2
• Patients with nonfibrotic (acute/subacute) HP demonstrate a mean difference of 34% higher BAL lymphocytes compared to IPF patients (95% CI, 29-40%) 1
• The lymphocyte count in acute HP is typically higher than in fibrotic HP, with nonfibrotic cases showing mean differences of 25% higher than sarcoidosis (95% CI, 22-27%) 1
• BAL lymphocytosis >50% is particularly suggestive of HP and increases diagnostic confidence 3, 4

Other BAL Cell Populations

• Increased neutrophils (>3%) may be present in subacute HP 4
• Increased mast cells (>1%) can support the diagnosis 4
• The predominance of CD8+ T lymphocytes (suppressor cytotoxic lymphocytes) is characteristic 3, 5

Important Caveats About BAL Interpretation

• No single BAL lymphocyte threshold perfectly distinguishes HP from other ILDs, as the area under the curve for various thresholds (20%, 30%, 40%) ranges from 0.44-0.71 depending on the comparison disease 1
• BAL lymphocytosis may be reduced by systemic corticosteroid therapy, smoking, age, and disease severity 1
• The diagnostic value is highest when BAL is interpreted in conjunction with exposure history and HRCT findings, not in isolation 1, 2

Serum Antibody Testing

Antigen-Specific IgG Antibodies

• Serum precipitating antibodies (IgG) against suspected antigens indicate exposure but do not confirm disease 1, 2, 3
• Sensitivity ranges widely from 25-96% and specificity from 60-100%, reflecting significant heterogeneity in testing methods and antigens 1, 2
• In one large study of 400 patients, serum precipitins had 78% sensitivity and 69% specificity, with odds ratios of 2.7-10.4 for HP versus controls 1
• Critical pitfall: 20-60% of patients with positive precipitins may have no identifiable exposure, and 25-32% with negative precipitins have identifiable exposures 1

Limitations of Serology

• Results must be interpreted cautiously as they only indicate sensitization, not active disease 2, 6
• The lack of standardized antigen preparations and cutoff values limits reproducibility 1
• Serum testing is most useful when exposure history is unclear, helping identify putative antigens 2, 6

Physiologic Changes During Acute Episodes

Specific Inhalation Challenge (SIC) Response

• During acute reactions to antigen challenge, patients demonstrate fever >0.5°C (sensitivity 100%, specificity 82%) 1
• FVC drop ≥16% shows sensitivity of 76% and specificity of 81% 1
• PaO2 drop ≥3 mm Hg or SaO2 drop ≥3% demonstrates sensitivity of 88% and specificity of 82-86% 1
• A prediction score incorporating white blood cell differential and alveolar-arterial oxygen gradient showed 93% sensitivity and 95% specificity 1

Histopathological Findings (When Biopsy Performed)

Acute/Subacute HP Features

• Cellular interstitial pneumonia with mononuclear cell infiltration of alveolar walls 3, 7
• Cellular bronchiolitis affecting terminal bronchioles 2, 7
• Poorly formed nonnecrotizing granulomas (though isolated granulomas alone are not specific) 2, 3, 4
• Bronchiolocentric distribution of inflammation 7, 8

Diagnostic Algorithm for Laboratory Evaluation

When acute HP is suspected based on clinical presentation:

1. First-line testing: Obtain BAL with lymphocyte differential analysis before more invasive procedures 2, 6

   • Target: ≥30% lymphocytes strongly supports diagnosis
   • Also assess neutrophils and mast cells

2. Concurrent serum testing: Order antigen-specific IgG panels based on exposure history 2, 6

   • Positive results support exposure but require clinical correlation
   • Negative results do not exclude HP

3. If BAL shows <30% lymphocytes but clinical suspicion remains high, consider that corticosteroid use, smoking, or timing of BAL may affect results 1

4. Biopsy consideration: Reserve for cases where BAL, imaging, and exposure assessment do not yield confident diagnosis after multidisciplinary discussion 1, 2, 6

Common Pitfalls to Avoid

• Do not rely on serum precipitins alone due to high false-positive and false-negative rates 1, 2
• Do not use lack of BAL lymphocytosis to definitively exclude HP, as fibrotic HP may show lower lymphocyte counts (mean difference 21% vs IPF) 1
• Do not interpret isolated histopathologic findings (like granulomas) without clinical and radiologic context, as they occur in other ILDs 2
• Remember that up to 60% of HP cases may lack an identifiable antigen despite thorough investigation 2, 6