Emphysema and airway disease synergistically impair exercise tolerance in smokers: A CT-based study

Emphysema and airway disease are major pathological features in smokers, including those with chronic obstructive pulmonary disease (COPD); however, how these two distinct pathologies interact to impair exercise capacity remains poorly understood. This study aimed to comprehensively compare physical performance, body composition, and physical activity across four computed tomography (CT)-based phenotypes: emphysema-dominant (ED), airway disease-dominant (AD), both-dominant (Mixed), and neither-dominant (Mild).

This cross-sectional analysis used baseline data from a single-center prospective cohort of smokers enriched for COPD. Alongside spirometry and 6-minute walk distance (6MWD), chest CT was performed to quantify the low attenuation volume percentage (LAV%) and airway wall area (Pi10), which enabled classification into Mild, AD, ED, and Mixed phenotypes.

A total of 181 smokers (77.9% with COPD) were categorized into Mild, AD, ED, and Mixed groups (n = 62/33/55/31, respectively). The Mixed group exhibited a significantly shorter 6MWD compared with the Mild group. Furthermore, the ED and Mixed phenotypes showed greater dyspnea and oxygen desaturation during exercise. In multivariable analysis, both LAV% and Pi10 were independently associated with 6MWD after adjusting for relevant clinical covariates and muscle strength. A significant interaction between LAV% and Pi10 was observed, demonstrating their synergistic detrimental effect on 6MWD.

Emphysema and airway disease independently and synergistically contribute to impaired exercise tolerance in smokers. CT-based phenotyping, particularly identification of the Mixed phenotype, may be useful to stratify functional risk and guide targeted interventions for preserving physical function in this population.