Biological sex differences in the perception of CO₂-induced air hunger

Biological sex may mediate 'dyspnoea' during submaximal exercise, but whether it mediates air hunger (AH), a highly unpleasant form of dyspnoea, remains unclear.

Forty healthy adults (twenty females) completed 6-min of quiet breathing (rest) followed by a hyperoxic CO₂ rebreathing task to evoke AH. AH intensity (AH-I) and unpleasantness (AH-U) were measured every 30-s. The Multidimensional Dyspnoea Profile (MDP) was administered after CO₂ rebreathing.

Compared to males, AH-I and AH-U thresholds occurred at lower PETCO₂ in females (AH-I: 44.15 ± 2.81 vs 48.90 ± 4.47 mmHg, P < 0.001; AH-U: 43.86 ± 2.57 vs 47.59 ± 2.75 mmHg, P < 0.001) and after a smaller increase in PETCO₂ above resting PETCO₂ (AH-I: 7.04 ± 2.63 vs 10.08 ± 5.28 mmHg, P = 0.027; AH-U: 6.75 ± 2.22 vs 8.77 ± 2.99 mmHg, P = 0.020). AH-I and AH-U were higher in females than males at standardised absolute V̇_E of 25, 30 and 35 L/min (P < 0.05). AH-U, but not AH-I, remained higher (main effect of sex, P = 0.026) in females than males at standardised relative V̇_E of 20, 25, and 30 % MVV. More females (n = 9) than males (n= 4) terminated CO₂ rebreathing due to maximal AH perception (P = 0.001). Compared to males, females reported greater intensities of 'mental effort/concentration' (7 ± 3 vs 4 ± 3), 'tight/constricted lungs' (6 ± 3 vs 2 ± 2), and 'breathing work/effort' (6 ± 2 vs 4 ± 3) (all P < 0.05) on the MDP.

Our findings suggest that sex differences exist in the perception of AH, which are not entirely accounted for by sex differences in ventilatory capacity.