Physiological mechanisms of dyspnea: role of neural respiratory drive

“呼吸困难”是指人类在运动等身体压力条件下所经历的呼吸不适的主观意识。在一般人群和慢性心肺疾病患者中，呼吸困难的症状已经成为残疾和死亡的一个非常强大的独立预测因子。事实上，一般人群中大约10%的成年人和高达75%的晚期慢性阻塞性肺疾病成年人报告出现严重的呼吸困难，这损害了他们参加常规体育活动的能力。尽管呼吸困难的负担和影响很大，但这种症状的根本原因仍然知之甚少，而且在很大程度上没有得到充分的研究。因此，该研究计划的总体目标是通过(1)评估实验操作呼吸驱动对运动中感知到的呼吸困难评分的影响，从而更好地理解人类受试者呼吸困难的复杂生理机制；(2)评估吸气弹性负荷和吸气阻力负荷对运动中呼吸驱动和感知呼吸困难评分之间关系的单独影响；(3)确定呼吸驱动增加的来源是否影响呼吸困难的感知。未来的治疗方法可以更有效地缓解从健康到慢性心肺疾病的人类受试者的呼吸困难，这需要更好地理解这种普遍、复杂和潜在致残症状的确切生理机制，这将作为NSERC发现研究计划的结果出现。

“Dyspnea” refers to the subjective awareness of breathing discomfort experienced by humans under conditions of physical stress such as exercise. In the general population and in patients with chronic cardiopulmonary disease, the symptom of dyspnea has emerged as a very strong indepenent predictor of disability and death. Indeed, approximately 10% of adults in the general population and up to 75% of adults with advanced chronic obstructive lung disease report experiencing dyspnea so severe that it impairs their ability to participate in regular physical activity. Despite the high burden and impact of dyspnea, the underlying cause(s) of this symptom remain poorly understood and largely understudied. Thus, the general aim of the proposed research program is to better understand the complex physiological mechanisms of dyspnea in human subjects by (1) assessing the effects of experimentally manipulating the drive to breathe on ratings of perceived dyspnea during exercise, (2) assessing the separate effects of inspiratory elastic and inspiratory resistive loading on the relationship between the drive to breathe and ratings of perceived dyspnea during exercise and (3) determining whether the origin of increased drive to breath influences the perception of dyspnea. Future therapies that lead to more effective relief of dyspnea in human subjects from health to chronic cardiopulmonary disease await a better understanding of the precise physiological mechanisms of this prevalent, complex and potentially disabling symptom, which will emerge as a result of this NSERC Discovery research program.