Ventilatory stimulation with relative external dead space loading does not impact sex differences in exertional dyspnoea

Sex differences in respiratory responses to ventilatory stress may contribute to exercise tolerance and dyspnoea perception, with potential implications across health and respiratory disease. We hypothesized that dead space loading (DSL) normalized to 15% of forced vital capacity would increase exertional dyspnoea, exacerbate inherent sex-based differences in the respiratory system's response to exercise, and elicit higher diaphragmatic and extra-diaphragmatic respiratory muscle activity in females than in males. Forty healthy, non-smokers (20 males, 20 females; 24 ± 5 years old; maximal O₂ uptake: 96 ± 20% predicted) completed familiarization followed by two maximal incremental cycling tests on separate days with and without DSL in a randomized, single-blinded and counter-balanced order. Diaphragm activity was recorded using a multi-pair electrode oesophageal catheter, while extra-diaphragmatic inspiratory muscle activity was recorded with bipolar surface electrodes. DSL was 797 ± 114 mL in males and 585 ± 71 mL in females (P < 0.001). Dyspnoea ratings increased similarly in both sexes with DSL, with no sex differences during or after exercise. Minute ventilation was increased with DSL throughout exercise [peak-males: Δ16 L·min^-1·%peak work^-1, CI: (12,19), P < 0.001; females: Δ11 L·min^-1·%peak work^-1, CI: (8,15), P < 0.001], as well as indices of mechanical ventilatory constraints (e.g. tidal volume, power of breathing) at peak exercise in both sexes, where males had a greater increase with DSL for most variables than females. Diaphragm and extra-diaphragmatic activity were increased with DSL in both sexes, with a greater increase in extra-diaphragmatic activity in females near maximal exercise. These findings suggest that while sex differences in respiratory function and respiratory muscle activation exist, they do not necessarily translate to sex differences in dyspnoea perception during maximal incremental cycling. KEY POINTS: Sex differences in respiratory anatomy and function are known to influence dyspnoea perception during exercise; however, the effects of higher ventilatory demand and mechanical ventilatory constraints on these differences remain poorly understood. Using a simple-randomization, single-blinded and counter-balanced study design, we stimulated minute ventilation ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:msub><mml:mover><mml:mi>V</mml:mi> <mml:mo>̇</mml:mo></mml:mover> <mml:mi>E</mml:mi></mml:msub> <mml:annotation>${\dot V_{\mathrm{E}}}$</mml:annotation></mml:semantics> </mml:math> ) and increased mechanical ventilatory constraints during maximal incremental cycling using dead space loading (DSL) customized to 15% of each individual's forced vital capacity. Dyspnoea was assessed using a multidimensional approach during and immediately after exercise. Despite increases in the sensations of breathing work/effort, unsatisfied inspiration and unsatisfied expiration with DSL in both sexes, there were no sex differences in dyspnoea perception during exercise with DSL. DSL increased <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:msub><mml:mover><mml:mi>V</mml:mi> <mml:mo>̇</mml:mo></mml:mover> <mml:mi>E</mml:mi></mml:msub> <mml:annotation>${\dot V_{\mathrm{E}}}$</mml:annotation></mml:semantics> </mml:math> and indicators of mechanical ventilatory constraints in both sexes compared to control exercise. Both sexes experienced an increase in diaphragmatic and extra-diaphragmatic muscle activity, where females had a greater increase in extra-diaphragmatic activity with DSL than males.