D30-18 Mucus Plugging, Air Trapping and Emphysema in Healthy Young Adult Never-smokers, Young Adult Smokers With Preserved Lung Function (BEACON) and COPD Patients

Rationale Mucus plugging (MP), air trapping and emphysema are common radiological features observed in individuals with well-established COPD. However, it is unclear if these pathologies emerge in parallel or sequentially as individuals transition from health towards disease. We quantitatively compare the presence of MP, air trapping and emphysema in young adult smokers with preserved lung function, healthy young adult never-smokers, and patients with COPD. Methods We analysed three groups: (i) the British EArly COPD Network (BEACON) containing 30-45-year-old smokers (≥10 pack-years) with post-bronchodilator FEV1 ≥80% predicted, (ii) healthy, never-smokers aged 30-50 years (<100 lifetime cigarettes, pre-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. Quantitative indices of air trapping and emphysema derived using the disease probability measure (DPM) method. Results We included 399 BEACON participants (mean age 38±5 years; 61% male; median 16 [Inter Quartile Range, (IQR):13-21] pack-years). They were similar in age, sex and spirometric values to 65 healthy never-smokers, while 88 COPD participants were older (mean 74±7 years), had greater smoking exposure (median 48 [IQR:29-60] pack-years), higher symptom burden (median CAT score 19 [IQR:11-25]), and lower FEV1 (65±20% predicted). MP was uncommon in healthy controls (12.3%) and BEACON participants (11.3%), both with a median MP score of 0 (IQR 0-0;P=0.636). When present, BEACON participants more frequently had high MP scores (≥4 bronchopulmonary segments with a MP) than healthy controls (17.8% vs 0%). In contrast, mucus plugging was frequent in COPD (84.1%), with a median score of 3.5 (IQR 1-7;P< 0.001 vs both groups), and 63.5% had high MP scores. Across all groups, MPs were similarly distributed among lobes (Figure A). However, BEACON participants, relative to healthy never-smokers, exhibited greater air trapping (median 7.3% vs 4.7%;P<0.001) and more emphysema (0.05% vs 0.03%;P=0.036), but less than was observed in patients with COPD (air trapping 37.8%; P < 0.001; emphysema 7.2%; P < 0.001) (Figure B). Conclusions Mucus plugs showed no lobar predominance in any group, appearing similarly prevalent in healthy never-smokers and young adult smokers but markedly increased in COPD. Despite comparable prevalence, BEACON participants demonstrated greater air trapping and emphysema than healthy controls. Smoking-related air-trapping and emphysema may emerge before visually detected MP increases in COPD development.