D30-08 Worsening Lung Function Coupled With Severe Exacerbations Is Associated With Increased Rate of Bronchial Wall Thickening

Rationale Airway remodeling, including bronchial wall thickening, has a causal role in the development and progression of chronic obstructive pulmonary disease (COPD). Structural airway changes can potentially drive airflow limitation and exacerbation susceptibility, yet longitudinal data linking these processes are limited. Understanding how airway remodeling evolves in individuals who develop airflow limitation and experience severe exacerbations can clarify the relationship between structural and functional disease manifestations. Methods Bronchial wall thickening was quantified for 18 bronchial segments using the bronchial wall area to outer area ratio, an image-derived metric representing the proportion of the total bronchial cross-sectional area occupied by the wall. We examined long-term changes in bronchial wall thickening across all 18 bronchial segments for a subsample of participants from the COPDGene study who were classified as GOLD 0 at baseline. Participants were divided into 4 groups based on GOLD progression and severe exacerbations: GOLD progression with exacerbations (n = 63), GOLD progression without exacerbations (n = 63), no GOLD progression with exacerbations (n = 37), and no GOLD progression without exacerbations (n = 37). To account for repeated measures across bronchial segments and time, we employed linear mixed models to compare annual rates of bronchial wall thickening between GOLD progressors with severe exacerbations and all other groups. Importantly, we included random effects for the time by bronchial segment interaction term, along with random intercepts for subject, study center, and scanner model. The model was adjusted for age, BMI, sex, race, height, smoking status, lung density, and CT technical characteristics. Results The annual increase in bronchial wall thickening was 0.62 percentage-points (95% CI: 0.48, 0.78) for participants who progressed beyond GOLD 0 and experienced severe exacerbations during follow-up. This annual change was significantly higher compared to all other groups: 0.27 percentage-points (95% CI: 0.20, 0.36) higher than participants who progressed beyond GOLD 0 without severe exacerbations, 0.31 percentage-points (95% CI: 0.22, 0.40) higher than participants who remained GOLD 0 and experienced severe exacerbations, and 0.34 percentage-points (95% CI: 0.24, 0.44) higher than participants remained GOLD 0 without severe exacerbations. When compared by bronchial segment, the largest amount of bronchial wall thickening occurred in the lower lung regions. Conclusions Participants who developed airflow limitation and experienced exacerbations showed the greatest annual increase in bronchial wall thickening. These findings indicate that accelerated airway remodeling underlies both worsening lung function and increased exacerbation risk, supporting a concept that wall thickening is a driver of COPD pathogenesis rather than merely a consequence.