Yoshimura Kenji, Maekura Ryoji, Hiraga Toru, Miki Keisuke, Kitada Seigo, Miki Mari, Tateishi Yoshitaka, Mori Masahide
Department of Respiratory Medicine, National Hospital Organization Toneyama Hospital , Toyonaka-city, Osaka , Japan.
COPD. 2014 Dec;11(6):615-26. doi: 10.3109/15412555.2014.898038. Epub 2014 Jun 10.
The survival rate of chronic obstructive pulmonary disease (COPD) patients with severely reduced exercise capacity is extremely low. We recently identified three life-threatening pathophysiological conditions during cardiopulmonary exercise testing (CPET): (1) exercise-induced hypoxemia, (2) sympathetic overactivity, and (3) progressive respiratory acidosis at low-intensity exercise. The present prospective observation study aimed to determine whether these parameters constitute risk factors of mortality in moderate-to-very severe COPD. Ninety-six COPD patients were followed-up, monthly, for >3 years. Subsequently, spirometry and CPET were performed to examine parameters of exercise-induced hypoxemia ([PaO2 slope, mmHg/L · min(-1)] = Decrease in PaO2/ΔV˙ O2 (Difference in ΔV˙ O2 between at rest and at peak exercise)), progression of acidosis ([ΔpH/ΔV˙ O2,/L · min(-1)] = Decrease in pH/ΔV˙ O2), and sympathetic overactivity ([Δnorepinephrine (NE)/ΔV˙ O2, ng/mL/L · min(-1)] = Increase in NE/ΔV˙ O2). Univariate analysis revealed a significant association between the three conditions with increased mortality. Kaplan-Meier analysis showed that the quartile combining the steepest PaO2 slope (≤-55 mmHg/ΔV˙ O2 [L/min]), steepest decrease in arterial blood pH (≤ -1.72/ΔV˙ O2 [L/min]), and most rapid increase in plasma NE level (≥ 5.2 ng/VO2 [L/min]) during incremental exercise was associated with higher all-cause mortality. These conditions showed cumulative effects on COPD patients' survival. Multivariate analyses revealed that these three life-threatening factors are also independent predictors of mortality based on age, heart rate and PaO2 at rest, body mass index, and forced expiratory volume in 1 s. Thus, these new exercise-induced mortality risk factors may lead to more efficient pulmonary rehabilitation programs for COPD patients based on patient-specific exercise-induced pathophysiological profiles.
运动能力严重下降的慢性阻塞性肺疾病（COPD）患者的生存率极低。我们最近在心肺运动试验（CPET）期间确定了三种危及生命的病理生理状况：（1）运动性低氧血症，（2）交感神经过度活跃，以及（3）低强度运动时进行性呼吸性酸中毒。本前瞻性观察研究旨在确定这些参数是否构成中度至极重度COPD患者死亡的危险因素。对96例COPD患者进行了为期3年以上的每月随访。随后，进行了肺活量测定和CPET，以检查运动性低氧血症参数（[动脉血氧分压斜率，mmHg/L·min（-1）]=动脉血氧分压下降值/每分通气量变化量（静息与运动峰值时每分通气量的差值））、酸中毒进展（[pH变化量/每分通气量变化量，/L·min（-1）]=pH下降值/每分通气量变化量）和交感神经过度活跃（[去甲肾上腺素（NE）变化量/每分通气量变化量，ng/mL/L·min（-1）]=NE增加量/每分通气量变化量）。单因素分析显示这三种状况与死亡率增加之间存在显著关联。Kaplan-Meier分析表明，在递增运动期间，将最陡的动脉血氧分压斜率（≤-55 mmHg/每分通气量变化量[L/min]）、动脉血pH最陡下降（≤-1.72/每分通气量变化量[L/min]）和血浆NE水平最快升高（≥5.2 ng/每分通气量变化量[L/min]）相结合的四分位数与全因死亡率较高相关。这些状况对COPD患者的生存具有累积影响。多因素分析显示，基于年龄、静息心率和动脉血氧分压、体重指数以及第1秒用力呼气量，这三种危及生命的因素也是死亡率的独立预测因素。因此，这些新的运动诱导的死亡风险因素可能会根据患者特定的运动诱导病理生理特征，为COPD患者带来更有效的肺康复计划。
