Abstract Rationale Air trapping is a key physiological hallmark of COPD, and mucus plugging is also frequently observed in affected patients. Understanding how mucus plugs relate to localised air trapping during the transition from health to disease could better delineate the early stages of COPD development. We investigated if mucus plugging identified lobes with a greater air trapping in young adult never-smokers, young adult smokers with preserved lung function, and patients with COPD. Methods We analysed three groups: (i) healthy, never-smokers aged 30-50 years (100 lifetime cigarettes, pre-bronchodilator FEV1 ≥80%); (ii) the British EArly COPD Network (BEACON) containing 30-45-year-old smokers (≥10 pack-years) with post-bronchodilator FEV1 ≥80% predicted; and (iii) London COPD Exacerbation cohort (EXCEL) participants aged 40 years, with FEV1/FVC 0.7, and 10 pack-years. Standardised full inspiratory and full expiratory CT scans were analysed centrally (VIDA Diagnostics) and scored by four trained pulmonologists for MPs in each bronchopulmonary segment using a predefined system. Lobar functional small airway disease (air trapping) was quantified using the disease probability measure (DPM). Within each cohort, lobar DPM air trapping was compared between lobes with versus without mucus plugs. Results Across 65 healthy controls, 399 BEACON participants, and 88 COPD patients, mucus plugs were observed in 12.3%, 11.3%, and 84.1% of participants respectively. Among BEACON and COPD participants, lobes with mucus plugs exhibited significantly greater air trapping relative to lobes without plugs (median 11.3 Interquartile range, (IQR): 4.9-20.5% vs 7.0 IQR:4.8-12.9%;P0.001 and 41.2 IQR:24.6-54.4% vs 36.8 IQR:24.1-49.6%;P=0.0015 respectively). Among healthy controls, lobar air trapping did not differ between lobes with versus without plugs (median 5.0 IQR: 4.6-6.1% vs 4.7 IQR:4.1-5.6%;P=0.30). Of note, in all groups, some lobes lacking plugs still demonstrated substantial air trapping (Figure). Conclusions In both BEACON and COPD participants, lobes containing CT-visible mucus plugs exhibited significantly greater air trapping, whereas this association was not observed in healthy never-smokers. Despite a similar prevalence of mucus plugging, BEACON participants showed greater lobar air trapping than healthy controls, consistent with early smoking-related small airway abnormalities. These findings suggest that CT-visible mucus plugs in larger airways likely reflect more extensive disease in the peripheral/small airways, rather than directly causing local airflow obstruction. Mucus plugs and peripheral functional abnormalities may develop in parallel, or mucus plugging may arise secondarily to pre-existing small airway disease. Overall, mucus plugs serve as a marker of greater functional impairment in young adult smokers and COPD patients. This abstract is funded by: Supported by the National Heart and Lung Foundation, a Project Grant from Asthma + Lung UK (RP22F\2) and a consortium comprising AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, and Novartis.
Braddy-Green et al. (Fri,) studied this question.