Sex-differences in respiratory sensation and muscle function during conditions of physiological stress

我以前的NSERC资助的工作表明，在运动期间，女性：1）更有可能发展呼吸限制; 2）呼吸功更高; 3）操作肺容量增加; 4）呼吸困难的评分更高（即，与男性相比，我最近的NSERC发现基金（DG）的资助导致了两个新的发现，增加了我们对健康人类呼吸生理学性别差异的理解。首先，我们发现，除了在运动中报告更高的呼吸困难强度等级外，女性相对于男性经历了不同质量的呼吸困难。具体来说，女性明显更有可能选择呼吸困难的短语，暗示吸气困难和浅呼吸相对于男性。然而，这种呼吸感觉性别差异的确切生理机制仍然未知。我们的第二个重大发现是，健康女性在运动时与男性不同地使用吸气肌。具体来说，女性在锻炼时更依赖于她们的“肺外”吸气肌。为什么女性比男性更多地使用这些肌肉，以及相应的生理和感官后果也仍然未知。因此，这次NSERC DG更新将寻求扩大这两个最近的发现。最终，这项研究计划的长期目标是提高我们对生理应激增加条件下呼吸生理性别差异的理解。 短期目标1将系统地研究健康人呼吸困难强度和定性方面性别差异的生理机制。总体假设是，由于神经呼吸驱动（NRD）的增加，女性报告了更强烈的呼吸困难评级，而呼吸困难定性描述符的性别差异主要是由于NRD与呼吸系统机械输出[即神经机械解偶联（NMU）]之间关系的差异。短期目标2将研究在全身运动和吸气肌负荷期间呼吸肌募集的性别差异的机制和后果。总体假设是，女性比男性更多地使用其呼吸肌外吸气肌，作为以增加呼吸困难为代价最小化呼吸工作/疲劳的策略。这项为期5年的研究计划将加强我们对男性和女性在生理压力增加的情况下如何呼吸的基本理解，并将为呼吸感觉和肌肉招募的性别差异提供新的见解。最终，这项应用人体生理学研究计划将对我们设计更有效的干预措施以增强人类呼吸肌力量和运动耐受力的能力产生直接影响。

My previous NSERC funded work has shown that during exercise, women: 1) are more likely to develop ventilatory constraints; 2) have a higher work of breathing; 3) have increased operating lung volumes; and 4) experience more intense ratings of dyspnea (i.e., breathlessness) compared to men. Funding from my most recent NSERC Discovery Grant (DG) resulted in two novel discoveries that have increased our understanding of sex differences in respiratory physiology in healthy humans. First, we showed that in addition to reporting higher dyspnea intensity ratings during exercise, women experienced different qualities of dyspnea relative to men. Specifically, women were significantly more likely to select dyspnea phrases alluding to inspiratory difficulty and shallow breathing relative to men. However, the precise physiological mechanisms for this sex difference in respiratory sensation remain unknown. Our second major discovery was that healthy women recruit their inspiratory muscles differently than men during exercise. Specifically, women rely more heavily on their `extradiaphragmatic' inspiratory muscles during exercise. Why women recruit these muscles more than men and the corresponding physiological and sensory consequences also remain unknown. Accordingly, this NSERC DG renewal will seek to expand on these two recent discoveries. Ultimately, the long-term objective of this research program is to enhance our understanding of sex differences in respiratory physiology during conditions of increased physiological stress. Short-term objective 1 will systematically examine the physiological mechanism underlying sex differences in both the intensity and qualitative dimensions of dyspnea in healthy humans. The overarching hypothesis is that women report more intense dyspnea ratings due to an increase in neural respiratory drive (NRD), whereas sex differences in the qualitative descriptors of dyspnea are primarily due to differences in the relationship between NRD and the mechanical output of the respiratory system [i.e. neuromechanical uncoupling (NMU)]. Short-term objective 2 will examine the mechanisms and consequences of sex differences in respiratory muscle recruitment during both whole-body exercise and inspiratory muscle loading. The overarching hypothesis is that women recruit their extradiaphragmatic inspiratory muscles more than men as a strategy to minimize diaphragmatic work/fatigue at the expense of increased dyspnea. The proposed 5-year research program will enhance our fundamental understanding of how men and women breathe during conditions of increased physiological stress and will provide novel insight into sex differences in respiratory sensation and muscle recruitment. Ultimately, this applied human physiology research program will have a direct impact on our ability to design more effective interventions to enhance respiratory muscle strength and exercise tolerance in humans.