Resistive unloading of the respiratory system did not reverse the blunted ventilatory response to heavy exercise in older adults with obesity

Introduction: Obesity is associated with changes in respiratory function that may limit the ability to increase ventilation during exercise. We have shown that the ventilatory response to heavy exercise (i.e. Formula: see textE/Formula: see textCO 2 slope) is blunted in older adults with obesity, which is likely due to the presence of obesity-related mechanical constraints that are imposed on breathing. Whether resistive unloading of the respiratory system in older adults with obesity increases the ventilatory response to heavy exercise remains unclear. To test this hypothesis, we measured the ventilatory response to heavy exercise in older adults with and without obesity while breathing room air or a low-density helium-oxygen gas mixture (HeO 2 ). Methods: Sixteen older adults (65-75 years) were evaluated including 8 classified without obesity (age: 70 ± 4 yr, BMI: 23.8 ± 2.7 kg/cm2, 75% female) and 8 with obesity (age: 69 ± 2 yr, BMI: 35.2 ± 5.7 kg/cm2, 63% female). Participants completed 6 minutes of constant-load submaximal exercise followed by maximal incremental exercise breathing room air (RA) or heliox (21% O 2 / 79% Helium) in randomized single-blind order. The ventilatory response to exercise was defined as the slope of the relation between Formula: see textE and Formula: see textCO 2 from minute 6 of constant-load cycling to peak exercise. Results: The Formula: see textE/Formula: see textCO 2 slope from minute 6 of constant-load exercise to peak exercise was not significantly different across conditions in older adults without obesity (RA: 51.5 ± 14.5 vs. HeO 2 : 49.2 ± 18.3, P = 0.531) or with obesity (RA: 42.1 ± 5.5 vs. HeO 2 : 41.9 ± 8.3, P = 0.945). At peak exercise PETCO 2 was lower in participants without obesity when breathing HeO 2 (RA: 35.0 ± 5.0 mmHg vs. HeO 2 : 31.6 ± 5.6 mmHg, P = 0.004), however, it remained similar across conditions in participants with obesity (RA: 35.4 ± 2.9 mmHg vs. HeO 2 : 35.3 ± 3.8 mmHg, P = 0.886). Conclusion: Our data demonstrate that resistive unloading of breathing did not reverse the blunted ventilatory response in older adults with obesity. These results suggest that airway resistance may not play a major role in the blunting of the ventilatory response to heavy exercise in older adults with obesity. Funding source: R00HL164957, R01AG070262 This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.