Sex differences in the work of breathing during exercise are independent of forced vital capacity in healthy adults

During exercise, females have a higher work of breathing (Ẇ_B) than males for a given 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}_{\text {E}}$</mml:annotation></mml:semantics> </mml:math> ) ≥ 50-60 L min^-1, presumably due to sex differences in airway size. However, on average, males have greater forced vital capacity (FVC) than females, and the confounding effect of FVC on sex differences in Ẇ_B is unknown. To determine the effects of FVC and sex on Ẇ_B during exercise in healthy adults, 30 healthy adults (15 males, 15 females) completed spirometry and an incremental cycle exercise test to exhaustion. Throughout exercise, Ẇ_B was calculated based on oesophageal pressure and open-circuit spirometry. The Ẇ_B- <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:msub><mml:mover><mml:mi>V</mml:mi> <mml:mo>̇</mml:mo></mml:mover> <mml:mi>E</mml:mi></mml:msub> <mml:annotation>$ \dot {V}_{\text {E}}$</mml:annotation></mml:semantics> </mml:math> relationship was compared between the sexes across all participants and in seven males and seven females matched for FVC and age. Across all participants, FVC had no effect on the Ẇ_B- <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:msub><mml:mover><mml:mi>V</mml:mi> <mml:mo>̇</mml:mo></mml:mover> <mml:mi>E</mml:mi></mml:msub> <mml:annotation>$ \dot {V}_{\text {E}}$</mml:annotation></mml:semantics> </mml:math> relationship (P = 0.323), and females had a higher Ẇ_B than males at a <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:msub><mml:mover><mml:mi>V</mml:mi> <mml:mo>̇</mml:mo></mml:mover> <mml:mi>E</mml:mi></mml:msub> <mml:annotation>$ \dot {V}_{\text {E}}$</mml:annotation></mml:semantics> </mml:math> of 50 (P = 0.030), 60 (P = 0.023), 70 (P = 0.021) and 80 L min^-1 (P = 0.020). At a <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:msub><mml:mover><mml:mi>V</mml:mi> <mml:mo>̇</mml:mo></mml:mover> <mml:mi>E</mml:mi></mml:msub> <mml:annotation>$ \dot {V}_{\text {E}}$</mml:annotation></mml:semantics> </mml:math> of 35 ± 2 L min^-1, FVC was not associated with Ẇ_B (r²= 0.042, P = 0.278). Conversely, at a <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:msub><mml:mover><mml:mi>V</mml:mi> <mml:mo>̇</mml:mo></mml:mover> <mml:mi>E</mml:mi></mml:msub> <mml:annotation>$ \dot {V}_{\text {E}}$</mml:annotation></mml:semantics> </mml:math> of 70 ± 5 L min^-1, FVC was associated with Ẇ_B across all participants (r²= 0.164, P = 0.026), but not within each sex (males: r²= 0.077, P = 0.317; females: r²= 0.011, P = 0.714). In the males and females matched for FVC and age, females had a higher Ẇ_B than males at a <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:msub><mml:mover><mml:mi>V</mml:mi> <mml:mo>̇</mml:mo></mml:mover> <mml:mi>E</mml:mi></mml:msub> <mml:annotation>$ \dot {V}_{\text {E}}$</mml:annotation></mml:semantics> </mml:math> of 60 (P = 0.049), 70 (P = 0.019), 80 (P = 0.020) and 90 L min^-1 (P = 0.014). Overall, our findings indicate that sex differences in Ẇ_B during exercise are not influenced by male-female differences in FVC.