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

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.