Association between Airway Mucus Plugs on Computed Tomography and Respiratory Outcomes in Participants with COPD and with Preserved Spirometry: Findings from a Chinese Population

Abstract Rationale Airway mucus plugs are a prognostic marker in moderate-to-very severe chronic obstructive pulmonary disease (COPD), but their association with respiratory outcomes has been insufficiently evaluated among participants with preserved spirometry and asymptomatic COPD. Objectives To investigate the association between mucus plugs and respiratory outcomes among participants with COPD and with preserved spirometry. Methods This prospective community-based cohort study was conducted in China, from July 2019 to September 2024. Eligible participants completed baseline questionnaires, spirometry, and chest CT with follow-up. Mucus plugs were categorized as affecting 0, 1–2, or ≥ 3 lung segments. Respiratory outcomes included exacerbations, lung function decline, and spirometry-defined COPD development. Measurements and Main Results Overall, 1,939 participants (COPD: 847; preserved spirometry: 1,092) were included, and 1,740 (89%) completed the 3-year follow-up. Among participants with preserved spirometry, those with 1–2 or ≥ 3 mucus plugs had a higher exacerbation risk (RR 1.22, 95%CI 1.01–1.48; RR 1.42, 95%CI 1.11–1.81, respectively) than those without mucus plugs. Participants with ≥3 mucus plugs had a higher risk of spirometry-defined COPD development (18.2% vs. 7.6%, RR 1.71, 95%CI 1.05–2.78) and faster annual decline in FEV1/FVC than those without mucus plugs. Among participants with COPD, with mild-to-moderate COPD, or with asymptomatic COPD, the presence of ≥ 3 mucus plugs were associated with a higher total and moderate-to-severe exacerbation risk. Conclusions Baseline airway mucus plugs potentially associated with future exacerbations in participants with preserved spirometry and COPD, and may suggest an increased risk of spirometry-defined COPD development in those with preserved spirometry.