Neuro-physiological mechanisms of perceived respiratory discomfort (dyspnea) in humans under conditions of physiological stress

“呼吸困难”这个词用来描述人们意识到随着身体压力的增加(如锻炼)而增加的呼吸不适。在普通人群中，呼吸困难的症状是残疾和死亡的独立预测因素。在患有慢性肺病和/或心脏病的患者中，呼吸困难对运动不耐受和感觉到的与健康相关的低质量生活质量有重要影响。然而，呼吸困难的原因仍然知之甚少，很大程度上还没有得到充分的研究，这是我的研究计划的主要重点。因此，拟议的研究将系统地检验这一假设，即呼吸困难的强度、质量和不适是由呼吸动力和呼吸系统同步的机械/肌肉反应之间的复杂和动态相互作用调节的。为此，将在几种实验条件下检查和比较静止自行车上剧烈运动的详细生理和知觉反应，这些条件旨在增加呼吸动力，削弱呼吸系统的机械/肌肉反应，或两者兼而有之。此外，这些研究将(I)分离肺部、呼吸道和呼吸肌的感觉神经在呼吸困难原因中的作用，以及(Ii)通过比较旨在改变这些促成因素的活动的特定干预措施前后运动的生理和感知反应，研究中枢神经系统在形成呼吸困难表现中的作用。这些研究的结果不仅将加强我们对综合人类呼吸和感觉生理学的基本理解，也将为我们深入了解呼吸困难的原因以及在健康和疾病中缓解呼吸困难的机制提供有价值的见解。

"Dyspnea" is the term used to describe the awareness of increased breathing discomfort that accompanies an increase in physical stress (e.g., exercise) in humans. In the general population, the symptom of dyspnea is an independent predictor of disability and death. In patients with chronic lung and/or heart disease, dyspnea contributes importantly to exercise intolerance and perceived poor health-related quality-of-life. Nevertheless, the causes of dyspnea remain poorly understood, largely understudied and represent the primary focus of my research program. Accordingly, the proposed studies will systematically test the hypothesis that the intensity, quality and unpleasantness of dyspnea is modulated by a complex and dynamic interaction between the drive to breathe and the simultaneous mechanical/muscular response of the respiratory system. To this end, detailed physiological and perceptual responses to strenuous exercise on a stationary bicycle will be examined and compared under several experimental conditions designed to increase the drive to breathe, impair the mechanical/muscular response of the respiratory system or both in combination. In addition, these studies will (i) isolate the role of the sensory nerves in the lungs, airways and breathing muscles in dyspnea causation and (ii) examine the role of the central nervous system in shaping the expression of dyspnea by comparing physiological and perceptual responses to exercise before and after specific interventions designed to alter the activity of these contributory factors. The results from these studies will not only enhance our fundamental understanding of integrative human respiratory and sensory physiology, they will provide valuable insight into the mechanisms of dyspnea causation and, by extension, dyspnea relief in both health and disease.