Uncoupling of central airway pruning and emphysema severity in COPD: a quantitative CT analysis

Abstract Background The structural alterations of the airway tree in chronic obstructive pulmonary disease (COPD) exhibit significant heterogeneity. However, the precise relationship between airway remodeling and emphysema, particularly how they interact across different airway generations and disease severities, remains incompletely understood. Methods Using high-resolution quantitative computed tomography (qCT) paired with a customized 3D graph-based framework, we evaluated the morphological features of the airway tree in patients with COPD ( n = 377) and those with pure emphysema ( n = 99). Multi-variable analysis of covariance (ANCOVA) was rigorously employed to evaluate metrics across different GOLD stages. To isolate independent airway phenotypes, the models adjusted for standard clinical confounders (age, sex, height, weight, and smoking pack-years), the emphysema index (percentage of low attenuation area, LAA%), and an algorithmic covariate (Total Airway Branch Count [TAC]) specifically utilized to eliminate segmentation depth bias. Results Multivariate models revealed a distinct pathophysiological divergence between airway compartments. After full adjustment for clinical and algorithmic confounders, central airways demonstrated robust emphysema-independent remodeling: the COPD group exhibited significantly fewer visible central branches (F = 17.388, P < 0.001) and greater absolute wall thickness (Pi10, F = 40.456, P < 0.001) compared to the pure emphysema group. Conversely, the unadjusted group differences in mean central diameter and network heterogeneity (Diameter CV) completely vanished post-adjustment ( P = 0.6055 and P = 0.4326, respectively), confirming that these proximal variations were mathematical artifacts driven by peripheral branch pruning rather than true truncal dilation. Furthermore, macroscopic total airway volume showed no independent inter-group discrepancy ( P = 0.1581). Network dimensions, including Diameter CV and truncal-to-peripheral diameter ratios, were found to be heavily coupled with and driven by emphysema severity ( P < 0.001), reflecting parenchymal-destructive structural disproportion during disease progression. Conclusions Airway remodeling in COPD is anatomically heterogeneous. Peripheral airway changes and network heterogeneity are mechanically coupled with emphysema severity, whereas central airway wall thickening and truncal “pruning” represent independent pathological trajectories. The complete attenuation of proximal size and volumetric discrepancies after full covariate adjustment underscores the necessity of rigorously controlling for anthropometric scales and algorithmic segmentation depths to achieve precise, artifact-free COPD phenotyping.