Department of Medicine and Queen's University and Kingston Health Sciences Centre, Kingston, Ontario, Canada.
Department of Chest Diseases, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
J Appl Physiol (1985). 2019 Oct 1;127(4):1107-1116. doi: 10.1152/japplphysiol.00341.2019. Epub 2019 Aug 1.
The mechanisms linking reduced diffusing capacity of the lung for carbon monoxide (Dl) to dyspnea and exercise intolerance across the chronic obstructive pulmonary disease (COPD) continuum are poorly understood. COPD progression generally involves both Dl decline and worsening respiratory mechanics, and their relative contribution to dyspnea has not been determined. In a retrospective analysis of 300 COPD patients who completed symptom-limited incremental cardiopulmonary exercise tests, we tested the association between peak oxygen-uptake (V̇o), Dl, and other resting physiological measures. Then, we stratified the sample into tertiles of forced expiratory volume in 1 s (FEV) and inspiratory capacity (IC) and compared dyspnea ratings, pulmonary gas exchange, and respiratory mechanics during exercise in groups with normal and low Dl [i.e., <lower limit of normal (LLN)] using Global Lung Function Initiative reference values. Dl was associated with peak V̇o ( = 0.006), peak work-rate ( = 0.005), and dyspnea/V̇o slope ( < 0.001) after adjustment for other independent variables (airway obstruction and hyperinflation). Within FEV and IC tertiles, peak V̇o and work rate were lower ( < 0.05) in low versus normal Dl groups. Across all tertiles, low Dl groups had higher dyspnea ratings, greater ventilatory inefficiency and arterial oxygen desaturation, and showed greater mechanical volume constraints at a lower ventilation during exercise than the normal Dl group (all < 0.05). After accounting for baseline resting respiratory mechanical abnormalities, Dl<LLN was consistently associated with greater dyspnea and poorer exercise performance compared with preserved Dl. The higher dyspnea ratings and earlier exercise termination in low Dl groups were linked to significantly greater pulmonary gas exchange abnormalities, higher ventilatory demand, and associated accelerated dynamic mechanical constraints. Our study demonstrated that chronic obstructive pulmonary disease patients with diffusing capacity of the lung for carbon monoxide (Dl) less than the lower limit of normal had greater pulmonary gas exchange abnormalities, which resulted in higher ventilatory demand and greater dynamic mechanical constraints at lower ventilation during exercise. This, in turn, led to greater exertional dyspnea and exercise intolerance compared with patients with normal Dl.
一氧化碳弥散量（Dl）降低与呼吸困难和运动不耐受在慢性阻塞性肺疾病（COPD）连续体中的联系机制尚不清楚。COPD 的进展通常涉及 Dl 下降和呼吸力学恶化，其对呼吸困难的相对贡献尚未确定。在对完成症状限制递增心肺运动试验的 300 例 COPD 患者的回顾性分析中，我们测试了峰值摄氧量（V̇o）、Dl 与其他静息生理指标之间的相关性。然后，我们根据 1 秒用力呼气量（FEV）和吸气量（IC）的 tertiles 将样本分层，并比较了使用全球肺功能倡议参考值时 Dl 正常[即，<正常值下限（LLN）]和 Dl 低[即，<LLN]组的呼吸困难评分、肺气体交换和运动期间的呼吸力学。调整其他独立变量（气道阻塞和过度充气）后，Dl 与峰值 V̇o（=0.006）、峰值工作率（=0.005）和呼吸困难/V̇o 斜率（<0.001）相关。在 FEV 和 IC tertiles 内，低 Dl 组的峰值 V̇o 和工作率均低于正常 Dl 组（<0.05）。在所有 tertiles 中，低 Dl 组的呼吸困难评分更高、通气效率更低、动脉血氧饱和度更低，并且在运动时较低的通气下显示出更大的机械容积限制（均 <0.05）。在考虑到基线静息呼吸力学异常后，与保留 Dl 相比，Dl <LLN 始终与更大的呼吸困难和更差的运动表现相关。低 Dl 组的呼吸困难评分较高和运动更早终止与肺气体交换异常明显更大、通气需求更高以及相关的动态机械限制加速有关。我们的研究表明，一氧化碳弥散量（Dl）低于正常值下限的慢性阻塞性肺疾病患者有更大的肺气体交换异常，这导致在运动时较低的通气下需要更高的通气需求和更大的动态机械限制。这反过来又导致与正常 Dl 的患者相比，更大的运动性呼吸困难和运动不耐受。
