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

Abstract

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. 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. 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. Multiple components, including age at onset, allergic sensitization, airway fungal burden, and HAM, were associated with difficult-to-treat ABPA.