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

“呼吸困难”是一个术语，用来描述随着身体压力（如运动）的增加而增加的呼吸不适的意识。在一般人群中，呼吸困难的症状是残疾和死亡的独立预测因子。在慢性肺病和/或心脏病患者中，呼吸困难对运动不耐受和感知健康相关生活质量差有重要影响。然而，呼吸困难的原因仍然知之甚少，在很大程度上没有得到充分的研究，这是我研究计划的主要重点。因此，所提出的研究将系统地验证这样的假设，即呼吸困难的强度、质量和不愉快是由呼吸驱动和呼吸系统同时的机械/肌肉反应之间复杂的动态相互作用调节的。为此，将在几个实验条件下检查和比较在固定自行车上剧烈运动的详细生理和知觉反应，这些实验条件旨在增加呼吸的动力，损害呼吸系统的机械/肌肉反应，或两者兼而有之。此外，这些研究将(i)分离肺、气道和呼吸肌的感觉神经在呼吸困难病因中的作用，（ii）通过比较特定干预之前和之后对运动的生理和知觉反应来检查中枢神经系统在形成呼吸困难表达中的作用，这些干预旨在改变这些促成因素的活动。这些研究的结果不仅将增强我们对综合人类呼吸和感觉生理学的基本理解，而且将为呼吸困难的病因机制提供有价值的见解，进而为健康和疾病的呼吸困难缓解提供有价值的见解。

"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.