Refractory phenotype of Aspergillus-sensitized asthma with bronchiectasis and allergic bronchopulmonary aspergillosis

Background: Sensitization to Aspergillus, mucus plugs, and bacterial colonization may coexist and relate to a refractory phenotype during follow-up in asthma with bronchiectasis and allergic bronchopulmonary aspergillosis (ABPA). Objective: This study aimed to clarify the features of Aspergillus-sensitized refractory asthma with bronchiectasis and determine the refractory phenotype in this population and ABPA. Methods: This study included cases of the oldest available Aspergillus fumigatus–specific IgE data and chest computed tomography images from a nationwide survey of refractory asthma with bronchiectasis. The characteristics of the A fumigatus–IgE positive (Af sIgE⁺) group were investigated and compared with its nonsensitized counterpart (Af sIgE⁻) and ABPA group. Cluster analysis was conducted to determine the refractory phenotype. Results: The Af sIgE⁺ group (n = 35) demonstrated type 2 inflammation levels intermediate between the ABPA (n = 42) and Af sIgE⁻ (n = 38) groups while exhibiting higher blood monocyte counts than the Af sIgE⁻ group. Cluster analysis conducted in patients with ABPA and Af sIgE⁺ newly determined 2 clusters: one was characterized by a younger age of asthma onset with fungal detection in sputum, and the other was characterized by mucus plugs and inflammation with eosinophils and monocytes, which was significantly related to mucus plugs, airflow limitation, and trend to show exacerbation. In the latter cluster, mucus plugs persisted, and 30% yielded Pseudomonas aeruginosa in the sputum <5 years later. Conclusion: The refractory phenotype with persistent mucus plugs was identified in Aspergillus-sensitized refractory asthma with bronchiectasis and ABPA. Mucus plug prevention is warranted.