How Do Sex and Cardiorespiratory Fitness Impact Pulmonary Diffusing Capacity?

Abstract

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. This study aimed to examine the independent and combined associations of sex and cardiorespiratory fitness ( V̇ O 2peak ) with pulmonary diffusing capacity (DL CO ) and its determinants (capillary blood volume, V C ; and membrane diffusing capacity, D M ) at rest and during exercise, while controlling for lung size. This retrospective study utilized general linear regression and linear mixed effects modeling to evaluate DL CO (adjusted for hemoglobin) and its determinants at rest and during exercise in n = 113 participants (57 female). Sex, V̇ O 2peak , and alveolar volume (V A ) all showed significant bivariate associations with diffusing capacity of the lung for carbon monoxide (DL CO ) when tested separately (all P < 0.001). In our final model, after accounting for V A , only sex remained significantly associated with resting DL CO ( P = 0.047), whereas V̇ O 2peak was associated with resting V C ( P = 0.009). No significant interaction effects were detected for resting data. After accounting for V A , exercise DL CO was significantly associated with sex but not V̇ O 2peak ( P < 0.001). A significant sex* V̇ O 2peak *intensity interaction was detected in exercise DL CO whereby individuals with higher V̇ O 2peak have greater exercise DL CO , and trained males have a greater DL CO compared with trained females ( Pinteraction < 0.001; males, P < 0.001; females, P < 0.001). Exercise V C was not associated with V̇ O 2peak or sex after accounting for V A , but a significant sex* V̇ O 2peak *intensity interaction effect on exercise V C was detected ( Pinteraction = 0.009; males, P = 0.039; females, P = 0.298). By examining the independent and combined associations of sex and V̇ O 2peak with DL CO and its determinants, our findings identified that the DL CO response to exercise is modified by the combined effects of sex and fitness.