Role of mucus plugs in refractory asthma with bronchiectasis: focus on plug location

<bold>Background and Aim:</bold> The role of airway mucus plugging in asthma pathophysiology is well-established. However, its relationship with infectious episodes and type 2 inflammation remains unclear in refractory asthma with bronchiectasis. As part of the BEXAS study (Nomura N, et al. <italic>Respir Res</italic> 2022; 23: 365), this study aimed to clarify the association between mucus plugging, infectious episodes, and type 2 inflammation, with a specific focus on plug location. <bold>Methods:</bold> Patients with refractory asthma complicated by bronchiectasis, but not with allergic bronchopulmonary aspergillosis, were included, if they had high-resolution CT images suitable for mucus score evaluation. Mucus plugging was scored separately for bilateral upper and lower lobes, as well as for the total lung. Cluster analysis was performed using mucus scores in the upper and lower lobes and the number of lobes affected by bronchiolitis. <bold>Results:</bold> Forty-two patients were included, and three distinct clusters were identified. CL 1 (n = 14) was characterized by lower-lobe-dominant mucus plugs, the highest number of bronchiolitis-affected lobes, frequent detection of Pseudomonas, systemic corticosteroid-requiring exacerbations, and bronchopneumonia. This cluster also exhibited the lowest FeNO and %FEV1. CL 2 (n = 6) showed high mucus scores in both lower and upper lobes, along with the highest FeNO levels. CL 3 (n = 22) had the lowest mucus scores overall. The degree of bronchiectasis was comparable among the three clusters. <bold>Conclusions:</bold> Lower-lobe-dominant mucus plugs may reflect the severest phenotype, characterized by frequent bronchiolitis involvement and infectious episodes. The location of mucus plugs may be clinically important.