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

American Journal of Respiratory and Critical Care Medicine, vol. 212

Abstract

Abstract 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. This abstract is funded by: NHLBI grants U01 HL089897 and U01 HL089856 and by NIH contract 75N92023D00011

Authors 9

1. D Baraghoshi

   National Jewish Health

   Affiliation as printed

   National Jewish Health , Denver, CO,

2. Matthew J. Strand

   National Jewish Health

   Affiliation as printed

   National Jewish Health , Denver, CO,

3. Tjeerd van der Veer Aachen

   Leiden University Medical Center

   Affiliation as printed

   Leiden University Medical Center , Leiden,

4. J.-P. Charbonnier
   Affiliation as printed

   Thirona , Nijmegen,

5. H A W M Tiddens

   Erasmus MC - Sophia Children’s Hospital

   Affiliation as printed

   Sophia Childrens Hosp , Rotterdam,

6. G L Kinney

   Colorado School of Public Health

   Affiliation as printed

   Colorado School of Public Health, University of Colorado , Aurora, CO,

7. Kendra A. Young

   Colorado School of Public Health

   Affiliation as printed

   Colorado School of Public Health , Aurora, CO,

8. David A. Lynch

   National Jewish Health

   Affiliation as printed

   Natl Jewish Health , Denver, CO,

9. J D Crapo

   National Jewish Health

   Affiliation as printed

   National Jewish Health , Denver, CO,