Establishing Aspergillus-Specific IgG Cut-Off Level for Chronic Pulmonary Aspergillosis Diagnosis: Multicenter Prospective Cohort Study.

Objectives: Aspergillus -specific IgG ( Asp -IgG) cut-off level in diagnosing chronic pulmonary aspergillosis (CPA) remains unknown.
Methods: We prospectively recruited participants with clinical suspicion of CPA in three centers in Taiwan during 2019 June to 2020 August. Serum Aspergillus fumigatus -specific IgG ( Asp -IgG) (Phadia, Uppsala, UPPS, Sweden) was examined. Optimal cut-off level was determined by Youden's index and validated.
Results: A total of 373 participants were recruited. In the derivation cohort ( n = 262), Asp -IgG had an area under the receiver-operating-characteristic curve (AUC) of 0.832. The optimal cut-off level was 40.5 mgA/L. While applying this cut-off level to the validation cohort ( n = 111), the sensitivity and specificity were 86.7% and 80.2%. Lowering the cut-off level from 40.5 to 27 mgA/L, the sensitivity was steady (30/36, 83.3% to 31/36, 86.1%) while specificity dropped from 81.9% (276/337) to 63.5% (214/337). Restricting CPA diagnosis to only chronic cavitary pulmonary aspergillosis (CCPA) and chronic fibrosing pulmonary aspergillosis (CFPA) yielded a cut-off level of 42.3 mgA/L in the derivation cohort with a sensitivity of 100% and specificity of 84.4% in the validation cohort.
Conclusions: Serum Asp -IgG performs well for CPA diagnosis and provides a low false-positive rate when using a higher cut-off level (preferably around 40 mgA/L).