Background <p>Traditionally, mucus plugs have been evaluated using two-dimensional computed tomography (CT) images through expert visual assessment, a process that requires substantial experience and specialized knowledge of airway anatomy. In the present study, we propose a novel approach employing three-dimensional CT (3D-CT) with semi-automated quantification, which can be performed in routine clinical practice without requiring expert readers. We aimed to demonstrate its feasibility and clinical relevance for assessing mucus plug burden and exacerbation severity in asthma.</p> Methods <p>This exploratory, single-center, retrospective study included 23 patients with asthma and a history of exacerbations. Using a clinically available 3D-CT application, we semi-automatically quantified bronchial endpoint count and bronchial volume in both stable and exacerbation phases, and calculated their percentage change. We further assessed correlations of these parameters with mucus plug scores and arterial blood gas measurements.</p> Results <p>The bronchial endpoint count and bronchial volume were significantly lower during exacerbations than during the stable phase; both showed a significant negative correlation with mucus plug scores during exacerbations. The percentage change of bronchial endpoint count and bronchial volume from the stable to exacerbation phase also correlated with mucus plug scores. The bronchial endpoint count and bronchial volume at exacerbation-related admission did not correlate with the PaO₂/FiO₂ (P/F) ratio; however, their percentage change from the stable phase to exacerbation-related admission significantly correlated with the P/F ratio.</p> Conclusions <p>Clinically available semi-automated 3D-CT analysis enables objective and reproducible quantification of bronchial endpoint count and bronchial volume during asthma exacerbations, eliminating the need for expert readers. Their percentage change from the stable to exacerbation phase not only reflect mucus plug burden but also correlate with oxygenation status. These imaging biomarkers enable objective and quantitative assessment of structural airway abnormalities, including airway narrowing, distal airway obstruction, and mucus impaction. They are not intended to replace conventional clinical or physiological assessment, but rather to provide complementary structural information regarding the underlying causes of physiological abnormalities, such as impaired oxygenation, when detected by physiological evaluation. Furthermore, such quantitative structural assessment may contribute to a better understanding of airway structural changes and airway dynamics during asthma exacerbations.</p>