Clinical Characteristics of Difficult‐To‐Treat Allergic Bronchopulmonary Aspergillosis and Its Prediction Score

ABSTRACT Background and Objective Administration of oral corticosteroids and/or azole antifungals for 4–6 months remains the standard treatment for allergic bronchopulmonary aspergillosis (ABPA). This study investigated the clinical characteristics of patients with difficult‐to‐treat ABPA who failed to achieve clinical remission within 6 months. Methods Among the participants of a nationwide survey conducted in Japan in 2020, treatment‐naïve patients with ABPA who satisfied Asano's criteria were enrolled in this study. Clinical remission was defined as stable disease without exacerbation for ≥ 6 months under minimal treatment (oral prednisolone: ≤ 5 mg/day and no antifungal medication). A risk prediction score for difficult‐to‐treat ABPA was developed and validated in an independent cohort comprising patients with ABPA from a prospective registration study in Japan. Results In total, 316 treatment‐naïve patients with ABPA were enrolled in the study. The median time to minimal treatment status was 4.8 months in the group receiving standard treatment. The clinical remission rate at 6 months after standard treatment was 51%. Age ≤ 50 years at onset of ABPA ( p = 0.04), serum A. fumigatus ‐specific IgE titer of ≥ 20 U A /mL ( p = 0.006), positive culture for Aspergillus spp. in the sputum/bronchial lavage fluid ( p = 0.05), and presence of high attenuation mucus (HAM; p = 0.10) were associated with difficult‐to‐treat ABPA. The number of positive indicators indicated the risk of failure of standard treatment to yield clinical remission within 6 months in the derivation ( n = 87, p < 0.001) and validation ( n = 64, p = 0.009) cohorts. Conclusion Multiple components, including age at onset, allergic sensitization, airway fungal burden, and HAM, were associated with difficult‐to‐treat ABPA.