Mixed Mucus Plug-Emphysema Subtype and Acute Exacerbation in Chronic Obstructive Pulmonary Disease

BACKGROUND: Conventional clinical assessments inadequately capture chronic obstructive pulmonary disease (COPD) heterogeneity. Quantitative computed tomography metrics may enable refined phenotyping and improved prognostic assessment. RESEARCH QUESTION: What is the prognostic value of quantitative computed tomography-derived mucus plugs and emphysema for acute exacerbations in COPD? STUDY DESIGN AND METHODS: This prospective cohort study collected clinical data, chest computed tomography, and pulmonary function tests from patients with COPD. Patients were stratified by mucus plug score (cutoff: 4) and emphysema severity (%LAA-950 cutoff: 5%). Multivariate logistic regression analysis was performed to assess the association between subgroups and acute exacerbations. Stratified analysis was employed to evaluate both independent and combined effects. RESULTS: A total of 215 patients were categorized into four subgroups: low mucus/low emphysema (n=61), low mucus/high emphysema (n=46), high mucus/low emphysema (n=62), and high mucus/high emphysema (n=46). Compared with the low mucus/low emphysema group, the risk of acute exacerbation increased progressively across the other three subgroups, with adjusted ORs of 2.885 (95%CI:1.060-8.166, P=0.041), 3.134 (95%CI:1.212-8.540, P=0.021), and 3.297 (95%CI:1.096-10.298, P=0.036). Additionally, each 1-point increase in the mucus plug score was associated with a 1.1-fold higher risk of acute exacerbation (OR 1.111, 95%CI: 1.005-1.232, P=0.041). The association between higher mucus plugs (≥4 vs. <4) and acute exacerbations was statistically significant only in the low emphysema subgroup (OR 3.318, 95%CI: 1.114-10.731, P=0.036). INTERPRETATION: Quantitative computed tomography-defined mucus plugs and emphysema jointly identify clinically meaningful COPD subgroups and predict exacerbations, supporting their use for personalized risk stratification and targeted prevention.