How Do Sex and Cardiorespiratory Fitness Impact Pulmonary Diffusing Capacity?

Abstract

INTRODUCTION Physiological outcomes, like pulmonary diffusing capacity, can be impacted by non-modifiable (e.g., biological sex) and modifiable (e.g., cardiorespiratory fitness) factors. The quantification of potential combined, interactive effects of these factors remains unreported in the literature. PURPOSE To examine the independent and combined associations of sex and cardiorespiratory fitness (V̇O2peak) with pulmonary diffusing capacity (DLCO) and its determinants (capillary blood volume, VC; and membrane diffusing capacity, DM) at rest and during exercise, while controlling for lung size. METHODS This retrospective study utilized general linear regression and linear mixed effects modelling to evaluate DLCO (adjusted for hemoglobin) and its determinants at rest and during exercise in n = 113 participants (57 female). RESULTS Sex, V̇O2peak, and VA all showed significant bivariate associations with DLCO when tested separately (all P < 0.001). In our final model, after accounting for VA, only sex remained significantly associated with resting DLCO (P = 0.047), whereas V̇O2peak was associated with resting VC (P = 0.009). No significant interaction effects were detected for resting data. After accounting for VA, exercise DLCO was significantly associated with sex but not V̇O2peak (P < 0.001). A significant sex*V̇O2peak*intensity interaction was detected in exercise DLCO whereby individuals with higher V̇O2peak have greater exercise DLCO, and trained males have a greater DLCO compared to trained females (Pinteraction < 0.001; males, P < 0.001; females, P < 0.001). Exercise VC was not associated with V̇O2peak or sex after accounting for VA, but a significant sex*V̇O2peak*intensity interaction effect on exercise VC was detected (Pinteraction = 0.009; males, P = 0.039; females, P = 0.298). CONCLUSIONS By examining the independent and combined associations of sex and V̇O2peak with DLCO and its determinants, our findings identified that the DLCO response to exercise is modified by the combined effects of sex and fitness.