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

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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.