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 CO₂ 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 with males. Fifteen healthy young females and 15 age-matched males completed lung function testing, followed by a modified Duffin CO₂ rebreathing test. Pulmonary ventilation, breathing pattern, partial pressure of end-tidal CO₂ ([Formula: see text]), operating lung volumes (to estimate respiratory mechanical load), and perceived breathing discomfort and unpleasantness (modified Borg 0-10 scale) were acquired throughout CO₂ rebreathing. Linear mixed modeling was used to determine between-sex differences in ventilatory and perceptual parameters throughout CO₂ 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 was greater in females than in males (both P < 0.05). When accounting for the magnitude of between-group 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.NEW & NOTEWORTHY Despite past findings providing mechanistic insights into biological sex differences in dyspnea sensation during exercise, it remains unclear how biological sex differences in respiratory/structure function regulate the perception of dyspnea during progressive hypercapnia. Our results show that females report greater perceived breathing discomfort and unpleasantness than males during progressive hypercapnia. When accounting for the magnitude of between-group differences in end-inspiratory lung volume during hypercapnia, breathing discomfort and unpleasantness were similar between the sexes.