Operating lung volume and perceived dyspnea during progressive hypercapnia: the effect of biological sex

Females often report greater breathing discomfort and unpleasantness than males during exercise, secondary to a greater respiratory mechanical load for a given level of ventilation. However, sex differences in breathing discomfort/unpleasantness and the relative influence of respiratory mechanics during hypercapnia (increased arterial CO 2 tension) are poorly understood. We compared ventilatory and perceptual parameters during progressive hypercapnia in young healthy females and males. We hypothesized that heightened dyspnea during hypercapnia in females would be associated with greater mechanical loads, compared to males. Fifteen healthy young females and 15 age-matched males completed lung function testing, followed by a modified Duffin CO 2 rebreathing test. Pulmonary ventilation, breathing pattern, partial pressure of end-tidal CO 2 (P ET CO 2 ), operating lung volumes (to estimate respiratory mechanical load), and perceived breathing discomfort and unpleasantness (modified Borg 0-10 scale) were acquired throughout CO 2 rebreathing. Linear mixed modelling was used to determine between-sex differences in ventilatory and perceptual parameters throughout CO 2 rebreathing. Pulmonary ventilation and tidal volume were lower, and end-inspiratory lung volume (EILV), perceived breathing discomfort and unpleasantness were greater in females than males during hypercapnia (all p<0.05). The rise in breathing discomfort/unpleasantness ratings relative to pulmonary ventilation were greater in females than males (both p<0.05). When accounting for the magnitude of between groups differences in EILV during hypercapnia, breathing discomfort and unpleasantness were similar between the sexes. These data suggest that the heightened perceptual consequence of greater EILV reflects an increased awareness of higher inspiratory mechanical loads during hypercapnia in females.