Optimal ImmunoCAP Aspergillus fumigatus-Specific IgE Threshold for Detecting Allergic Bronchopulmonary Aspergillosis in Adults With Asthma: A Diagnostic Accuracy Study.

Abstract

Background: Allergic bronchopulmonary aspergillosis (ABPA) requires screening in adults with asthma using Aspergillus fumigatus-specific IgE (Af-IgE). The current Af-IgE threshold of 0.35 kUA/L has low specificity, leading to unnecessary downstream testing.

Objectives: To determine an optimal Af-IgE threshold that maintains high sensitivity while improving specificity for ABPA screening in adults with asthma.

Methods: We performed a diagnostic accuracy study of prospectively collected data using distinct derivation and validation cohorts in a tertiary care setting. The index test was ImmunoCAP Af-IgE at thresholds of 0.35, 0.70 and 0.90 kUA/L. The reference standard was the 2024 ISHAM-ABPA criteria applied by investigators aware of all test results.

Results: We included 543 consecutive asthmatic subjects investigated for possible ABPA in the derivation cohort (July 2017-September 2018) and 375 subjects with established asthma and ABPA in the validation dataset (January 2020-December 2023). ABPA prevalence was 19.5% (106/543) in derivation and 69.6% (261/375) in validation cohorts. Bayesian latent class analysis estimated a 0.3 kUA/L cut-off but did not improve specificity; frequentist analysis showed model misfit. In the validation cohort, increasing the threshold from 0.35 to 0.70 kUA/L improved specificity from 66.7% (95% CI, 57.6-74.7) to 72.8% (95% CI, 64.0-80.1; p = 0.016) without significant sensitivity reduction (100% to 98.9%; 95% CI, 96.7-99.6; p = 0.25). No patients with bronchiectasis were missed. At 0.90 kUA/L, sensitivity significantly decreased (97.7%; 95% CI, 95.1-98.9; p = 0.031).

Conclusions: ImmunoCAP Af-IgE threshold of 0.70 kUA/L optimised diagnostic performance for ABPA screening in adults with asthma, potentially reducing unnecessary confirmatory testing.