Cutoffs for serum mold-specific IgG levels for hypersensitivity pneumonitis: a diagnostic test accuracy study of 219 subjects
Keywords:
hypersensitivity pneumonitis, interstitial lung disease, sarcoidosis, molds, exposure, biomarker, precipitins, idiopathic pulmonary fibrosisAbstract
Background: American Thoracic Society guidelines suggest serum specific IgG (sIgG) testing targeting potential antigens associated with hypersensitivity pneumonitis (HP). The diagnostic cutoffs of mold-sIgGs remain undefined and their performance based on pre- and post-test probabilities remain untested.
Methods: We conducted a diagnostic test accuracy study using a case-control design. We enrolled subjects with HP (cases), other interstitial lung diseases (ILDs, diseased controls), and healthy controls with/without mold exposure. We measured sIgG against Aspergillus fumigatus, Penicillium chrysogenum, Cladosporium herbarum, and Micropolyspora faeni using an automated, fluorescent enzyme immunoassay. Cutoffs were derived from the 95th percentile values among non-exposed healthy controls for individual sIgGs and Youden’s J-statistic for pooled sIgG (sum of four levels). We evaluated the performance characteristics of sIgG levels for HP diagnosis among subjects with ILDs.
Results: We included 219 subjects (mean age, 51.4 years; 50.2% women): 105 HP, 64 non-HP ILDs, and 50 healthy controls (25 non-exposed, 25 exposed). Cutoffs (mgA/L) were 33, 22, 34, 8, and 53, for A. fumigatus, P. chrysogenum, C. herbarum, M. faeni, and pooled sIgG levels, respectively. The 4-mold panel (positive if any sIgG exceeded cutoff) showed 57.1% sensitivity and 78.1% specificity for HP diagnosis among ILD subjects. The pooled sIgG test (positive likelihood ratio, 3.29; negative likelihood ratio, 0.51) shifted post-test probability of HP diagnosis from 44% (for a negative test) to 84% (for a positive test).
Conclusion: Mold-specific IgGs, when used at our proposed cutoffs, significantly alter post-test diagnostic probabilities; thus, can be used as an adjunct in multi-component HP diagnosis.
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