INTRODUCTION:
Lung diffusing capacity (DL) is determined by membrane diffusive capacity (Dm), pulmonary capillary blood volume (Vc), and blood conductance, all of which may be influenced by both hypoxic exposure (1) and body position (e.g., upright vs supine) (2). This study aimed to examine the dynamic contributions of hemodynamic and membrane components to alveolar–capillary diffusion from rest to maximal cycling exercise during acute hypoxic exposure and in the upright vs. supine position.
METHODS:
Twenty-six healthy participants (age 27±4 years; VO₂max 48.9±7.1 ml·kg⁻¹·min⁻¹; 13F) underwent DL assessment at rest, during submaximal (0.8 W·kg⁻¹) and maximal cycling exercise in both upright and supine position, under normoxic (FiO₂ 20.9%) and hypoxic (FiO₂ 13.6%) conditions. DL and its vascular (Vc) and membrane (DmCO) components were determined using the single-breath DLCO and DLNO technique.
RESULTS:
From rest to maximal exercise, DLCO was higher in hypoxia compared to normoxia (FiO₂ main effect, all p<0.001) and in the supine compared to the upright position (position main effect, all p<0.001), with no significant FiO₂-by-position interaction. On average, compared with normoxia upright, DLCO increased by 11% in normoxia supine, 19% in hypoxia upright, and 27% in hypoxia supine. This was accompanied by a greater Vc in hypoxic conditions (all p<0.01) and in the supine position (all p<0.001), again without any significant interaction effect. Similar to DLCO, progressive increases from normoxia supine (22%) to hypoxia upright (29%) and supine (49%) were noticed for Vc. A significant FiO₂-by-position interaction effect was found for DmCO at rest (p=0.021) and at submaximal intensity (p<0.001), with a trend toward significance at maximal exercise (p=0.06). Post hoc analyses revealed that DmCO decreased similarly in normoxic supine (-14%), hypoxic upright (-21%), and hypoxic supine (-25%) conditions compared with normoxic upright cycling. This pattern was consistent from rest to maximal exercise. Finally, a reduction in alveolar volume (Va) was observed in the supine if compared to the upright position at rest (position effect, p<0.001) and during submaximal exercise (p=0.026).
CONCLUSION:
DLCO increased consistently across all experimental conditions compared with normoxic upright cycling, primarily due to a concomitant increase in Vc, which outweighed the reduction in Dm. This decrease in Dm, although unexpected, may be partially explained by the reduction in Va observed in the supine position (3). Notably, the increase in Vc and overall DL induced by passive central blood volume translocation in the normoxic supine position was comparable to that elicited by the vasoactive response triggered by hypoxia-induced pulmonary vasoconstriction in the hypoxic upright position. In the hypoxic supine condition, these effects appeared to be additive rather than interactive.
(1) Beretta et al., 2017
(2) Brotto et al., 2025
(3) Stam et al., 1983