Division of Pulmonary Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, Alberta, Canada.
J Physiol. 2021 Mar;599(5):1665-1683. doi: 10.1113/JP280913. Epub 2021 Jan 25.
Patients with mild chronic obstructive pulmonary disease (COPD) have an elevated ventilatory equivalent to CO production ( / ) during exercise, secondary to increased dead space ventilation. The reason for the increased dead space is unclear, although pulmonary microvascular dysfunction and the corresponding capillary hypoperfusion is a potential mechanism. Despite emerging evidence that mild COPD is associated with pulmonary microvascular dysfunction, limited research has focused on experimentally modulating the pulmonary microvasculature during exercise in mild COPD. The present study sought to examine the effect of inhaled nitric oxide (iNO), a selective pulmonary vasodilator, on / , dyspnoea and exercise capacity in patients with mild COPD. Experimental iNO increased peak oxygen uptake in mild COPD, secondary to reduced / and dyspnoea. This is the first study to demonstrate that experimental manipulation of the pulmonary circulation alone, can positively impact dyspnoea and exercise capacity in mild COPD.
Patients with mild chronic obstructive pulmonary disease (COPD) have an exaggerated ventilatory response to exercise, contributing to dyspnoea and exercise intolerance. Previous research in mild COPD has demonstrated an elevated ventilatory equivalent to CO production ( / ) during exercise, secondary to increased dead space ventilation. The reason for the increased dead space is unclear, although pulmonary microvascular dysfunction and the corresponding capillary hypoperfusion is a potential mechanism. The present study tested the hypothesis that inhaled nitric oxide (iNO), a selective pulmonary vasodilator, would lower / and dyspnoea, and improve exercise capacity in patients with mild COPD. In this multigroup randomized-control cross-over study, 15 patients with mild COPD (FEV = 89 ± 11% predicted) and 15 healthy controls completed symptom-limited cardiopulmonary exercise tests while breathing normoxic gas or 40 ppm iNO. Compared with placebo, iNO significantly increased peak oxygen uptake (1.80 ± 0.14 vs. 1.53 ± 0.10 L·min , P < 0.001) in COPD, whereas no effect was observed in controls. At an equivalent work rate of 60 W, iNO reduced / by 3.8 ± 4.2 units (P = 0.002) and dyspnoea by 1.1 ± 1.2 Borg units (P < 0.001) in COPD, whereas no effect was observed in controls. Operating lung volumes and oxygen saturation were unaffected by iNO in both groups. iNO increased peak oxygen uptake in COPD, secondary to reduced / and dyspnoea. These data suggest that mild COPD patients demonstrate pulmonary microvascular dysfunction that contributes to increased / , dyspnoea and exercise intolerance. This is the first study to demonstrate that experimental manipulation of the pulmonary circulation alone, can positively impact dyspnoea and exercise capacity in mild COPD.
患有轻度慢性阻塞性肺疾病（COPD）的患者在运动期间的 CO 产生通气当量（ / ）升高，这是由于死腔通气增加所致。增加死腔的原因尚不清楚，尽管肺微血管功能障碍和相应的毛细血管低灌注是潜在的机制。尽管有越来越多的证据表明轻度 COPD 与肺微血管功能障碍有关，但很少有研究关注在轻度 COPD 期间实验性调节肺微血管。本研究旨在研究吸入一氧化氮（iNO），一种选择性肺血管扩张剂，对轻度 COPD 患者的 / 、呼吸困难和运动能力的影响。实验性 iNO 增加了轻度 COPD 患者的峰值摄氧量，这是由于 / 和呼吸困难减少所致。这是第一项表明单独实验性调节肺循环就可以积极影响轻度 COPD 患者的呼吸困难和运动能力的研究。
患有轻度慢性阻塞性肺疾病（COPD）的患者在运动时会出现过度通气反应，导致呼吸困难和运动耐受力下降。以前在轻度 COPD 中的研究表明，由于死腔通气增加，运动时的 CO 产生通气当量（ / ）升高。增加死腔的原因尚不清楚，尽管肺微血管功能障碍和相应的毛细血管低灌注是潜在的机制。本研究检验了假设，即吸入一氧化氮（iNO），一种选择性肺血管扩张剂，将降低 / 和呼吸困难，并改善轻度 COPD 患者的运动能力。在这项多组随机对照交叉研究中，15 名轻度 COPD 患者（FEV = 89 ± 11%预测值）和 15 名健康对照者在呼吸正常氧或 40 ppm iNO 时完成了症状限制心肺运动测试。与安慰剂相比，iNO 可使 COPD 患者的峰值摄氧量（1.80 ± 0.14 对 1.53 ± 0.10 L·min ，P < 0.001）显著增加，而对照组则没有观察到这种作用。在等效的 60 W 工作率下，iNO 降低了 COPD 患者的 / 3.8 ± 4.2 个单位（P = 0.002）和呼吸困难 1.1 ± 1.2 个 Borg 单位（P < 0.001），而对照组则没有观察到这种作用。两组的肺容积和氧饱和度均不受 iNO 影响。iNO 增加了 COPD 患者的峰值摄氧量，这是由于 / 和呼吸困难减少所致。这些数据表明，轻度 COPD 患者表现出肺微血管功能障碍，这导致 / 增加、呼吸困难和运动耐受力下降。这是第一项表明单独实验性调节肺循环就可以积极影响轻度 COPD 患者的呼吸困难和运动能力的研究。
