Diagnostic Cutoffs and Clinical Utility of Recombinant Aspergillus fumigatus Antigens in the Diagnosis of Allergic Bronchopulmonary Aspergillosis

BACKGROUND: The clinical utility of IgE against recombinant Aspergillus fumigatus (rAsp)-specific antigens in allergic bronchopulmonary aspergillosis (ABPA) remains unclear. OBJECTIVE: To identify the optimal diagnostic cutoffs of rAsp-specific IgE in differentiating ABPA from A fumigatus-sensitized asthma (ASA), and define their utility in the diagnosis of ABPA. METHODS: We enrolled consecutive subjects with ASA and ABPA. IgE against rAsp f1, f2, f3, f4, and f6 was assayed in all the subjects. We evaluated 3 fixed cutoffs (0.35, 0.5, and 1.0 kU(A)/L) for their diagnostic performance in the entire cohort. We also divided the study population into derivation and validation cohorts. Cutoffs for rAsp-specific IgE were obtained using the receiver-operating characteristic analysis in the derivation cohort. We then evaluated the diagnostic performance of these cutoffs in the validation cohort. We further correlated rAsp-specific IgE levels in ABPA with asthma control, spirometry, imaging, and immunologic markers. RESULTS: We included 194 subjects (123 ABPA and 71 ASA). The statistically derived cutoffs proved superior to fixed cutoffs. IgE against rAsp f1 yielded the best combination of sensitivity (89%) and specificity (100%). The sensitivity and specificity of IgE against either rAsp f1 (cutoff, 4.465 kU(A)/L) or f2 (cutoff, 1.300 kU(A)/L) for diagnosing ABPA were 100% and 81%, respectively. The correlation between rAsp-specific IgE and most clinical parameters of ABPA was weak. CONCLUSIONS: IgE against rAsp f1 and f2 (using receiver-operating characteristic-derived cutoffs) were found to be the most useful in differentiating ABPA from ASA. Because this study was conducted at a single center, our results require further validation. (C) 2019 American Academy of Allergy, Asthma & Immunology