Tanaka Jun, Oguma Tsuyoshi, Ishiguro Takashi, Taniguchi Hirokazu, Nishiuma Teruaki, Tateno Hiroki, Matsumoto Hisako, Koshimizu Naoki, Ito Yutaka, Matsunaga Kazuto, Matsushima Hidekazu, Uchida Yoshitaka, Yokomura Koshi, Yasuba Hirotaka, Suzuki Junko, Hattori Shigeaki, Okada Naoki, Tomomatsu Katsuyoshi, Asano Koichiro
Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Department of Respiratory Medicine, Saitama Cardiovascular and Respiratory Center, Saitama, Japan.
Allergy. 2025 Sep;80(9):2531-2540. doi: 10.1111/all.16559. Epub 2025 May 2.
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/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.
口服糖皮质激素和/或唑类抗真菌药物治疗4 - 6个月仍是变应性支气管肺曲霉病（ABPA）的标准治疗方法。本研究调查了在6个月内未实现临床缓解的难治性ABPA患者的临床特征。
在2020年日本全国性调查的参与者中，纳入符合浅野标准且未接受过治疗的ABPA患者。临床缓解定义为在最小治疗（口服泼尼松龙：≤5mg/天且无抗真菌药物）下疾病稳定且无加重≥6个月。在一个独立队列中开发并验证了难治性ABPA的风险预测评分，该队列包括来自日本一项前瞻性注册研究的ABPA患者。
共有316例未接受过治疗的ABPA患者纳入本研究。接受标准治疗组达到最小治疗状态的中位时间为4.8个月。标准治疗6个月后的临床缓解率为51%。ABPA发病时年龄≤50岁（p = 0.04）、血清烟曲霉特异性IgE滴度≥20 U/mL（p = 0.006）、痰/支气管肺泡灌洗液中曲霉属培养阳性（p = 0.05）以及存在高密度黏液（HAM；p = 0.10）与难治性ABPA相关。阳性指标的数量表明在推导队列（n = 87，p < 0.001）和验证队列（n = 64，p = 0.009）中标准治疗在6个月内未能实现临床缓解的风险。
包括发病年龄、过敏致敏、气道真菌负荷和HAM在内的多个因素与难治性ABPA相关。
