Determinants of the diminished exercise capacity in patients with chronic obstructive pulmonary disease: looking beyond the lungs
Determinants of the diminished exercise capacity in patients with chronic obstructive pulmonary disease: looking beyond the lungs
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DOI：
10.1113/jp279135
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发表时间：
2020-01-19
影响因子：
5.5
通讯作者：
Richardson, Russell S.
中科院分区：
文献类型：
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作者：
Broxterman, Ryan M.;Hoff, Jan;Richardson, Russell S.
峰值摄氧量是预后、死亡率和生活质量的主要决定因素，在慢性阻塞性肺疾病 (COPD) 患者中会降低，越来越多的证据支持外周功能障碍（尤其是骨骼肌功能障碍）的重要作用。在患有严重慢性阻塞性肺病和活动匹配对照的患者中，在单腿膝伸肌运动 (KE) 期间的最大努力时评估肌肉氧输送和利用率，其中通气被假定为次最大。该策略消除了通气作为慢性阻塞性肺病患者运动能力的主要限制，从而实现和评估最大的肌肉功能。在最大 KE 期间，与对照组相比，COPD 患者对骨骼肌微血管系统的对流动脉氧输送以及随后对线粒体的扩散氧输送均减少。这些发现强调了肺部以外影响该患者群体运动能力的因素的重要性，并可能最终影响慢性阻塞性肺病患者的预后、死亡率和生活质量。峰值摄氧量 (V?O2peak) 是预后、死亡率和生活质量的主要决定因素，在慢性阻塞性肺疾病 (COPD) 患者中会降低。越来越多的证据支持外周肌，尤其是骨骼肌，在 COPD 导致的 V2O2 峰值降低中发挥着重要作用。然而，V?O2peak 的外围决定因素尚未在该队列中得到全面评估。因此，我们测试了这样的假设：与匹配的健康对照相比，COPD 患者的肌肉对流和扩散氧 (O-2) 运输以及骨骼肌 O-2 吸收峰值 (V?MO2peak) 均有所减少，即使通过小肌肉量锻炼将通气限制（即达到最大通气量）降至最低。在单腿膝伸肌运动期间，对 8 名严重 COPD 患者（1 秒用力呼气量 (FEV1) +/- SEM = 0.9 +/- 0.1 l，预测值的 30%）和 8 名对照患者的股动脉和静脉血样本以及腿部血流量（通过热稀释）进行峰值运动时的肌肉 O-2 转运和利用率进行评估。肌肉对流 O-2 输送（0.44 +/- 0.06 对比 0.69 +/- 0.07 l min(-1)，P < 0.05）和肌肉扩散 O-2 电导（6.6 +/- 0.8 对比 10.4 +/- 0.9 ml min(-1) mmHg(-1)，P < 0.05）与以下患者相似，均降低了 1/3： COPD 患者的 V?MO2 峰值减弱（0.27 +/- 0.04 vs. 0.42 +/- 0.05 l min(-1)，P < 0.05）。当运动对心肺的限制最小化时，COPD 患者骨骼肌水平上 V?MO2peak 的对流和扩散决定因素大大减弱。这些发现强调了肺部以外因素的重要性，这些因素可能最终影响该人群的预后、死亡率和生活质量。
Key pointsPeak oxygen uptake, a primary determinant of prognosis, mortality and quality of life, is diminished in patients with chronic obstructive pulmonary disease (COPD), with mounting evidence supporting an important role for peripheral dysfunction, particularly within skeletal muscle. In patients with severe COPD and activity-matched controls, muscle oxygen transport and utilization were assessed at peak effort during single-leg knee-extensor exercise (KE), where ventilation is assumed to be submaximal. This strategy removes ventilation as the major constraint to exercise capacity in COPD, allowing maximal muscle function to be attained and evaluated. During maximal KE, both convective arterial oxygen delivery to the skeletal muscle microvasculature and subsequent diffusive oxygen delivery to the mitochondria were diminished in patients with COPD compared to control subjects. These findings emphasize the importance of factors, beyond the lungs, that influence exercise capacity in this patient population and may, ultimately, influence the prognosis, mortality and quality of life for patients with COPD. Peak oxygen uptake (V?O2peak), a primary determinant of prognosis, mortality and quality of life, is diminished in patients with chronic obstructive pulmonary disease (COPD). Mounting evidence supports an important role of the periphery, particularly skeletal muscle, in the diminished V?O2peak with COPD. However, the peripheral determinants of V?O2peak have not been comprehensively assessed in this cohort. Thus, the hypothesis was tested that both muscle convective and diffusive oxygen (O-2) transport, and therefore skeletal muscle peak O-2 uptake (V?MO2peak), are diminished in patients with COPD compared to matched healthy controls, even when ventilatory limitations (i.e. attainment of maximal ventilation) are minimized by using small muscle mass exercise. Muscle O-2 transport and utilization were assessed at peak exercise from femoral arterial and venous blood samples and leg blood flow (by thermodilution) in eight patients with severe COPD (forced expiratory volume in 1s (FEV1) +/- SEM = 0.9 +/- 0.1 l, 30% of predicted) and eight controls during single-leg knee-extensor exercise. Both muscle convective O-2 delivery (0.44 +/- 0.06 vs. 0.69 +/- 0.07 l min(-1), P < 0.05) and muscle diffusive O-2 conductance (6.6 +/- 0.8 vs. 10.4 +/- 0.9 ml min(-1) mmHg(-1), P < 0.05) were similar to 1/3 lower in patients with COPD than controls, resulting in an attenuated V?MO2peak in the patients (0.27 +/- 0.04 vs. 0.42 +/- 0.05 l min(-1), P < 0.05). When cardiopulmonary limitations to exercise are minimized, the convective and diffusive determinants of V?MO2peak, at the level of the skeletal muscle, are greatly attenuated in patients with COPD. These findings emphasize the importance of factors, beyond the lungs, that may ultimately influence this population's prognosis, mortality and quality of life.