慢性阻塞性肺疾病患者睡眠状态下的呼吸中枢驱动

Chronic obstructive pulmonary disease (COPD) characterised with airflow limitation is a common disease and is one of the leading causes of death in the world. Underlying mechanisms of dyspnea, limitation of exercise and respiratory failure in patients with COPD may be related to neural respiratory drive. Research on COPD (eg, exercise testing) is usually taken place during daytime rather than at night for convenient or other reasons. However, Sleep-related hypoventilation has been demonstrated in COPD, particularly during rapid eye movement (REM) stage, with associated oxygen desaturation although blood gases could be normal during daytime. There is evidence that patients with COPD are more likely to die at night and that nocturnal oxygen desaturation is more serious in patients with co-existing COPD and obstructive sleep apnea than that in patients with COPD alone. It is not clear whether nocturnal oxygen desaturation or respiratory failure in patients with COPD is mainly due to increase in upper airway resistance or reduction of neural respiratory drive. In this project we will assess neural respiratory drive and upper airway resistance by recording diaphragm EMG and upper airway pressure simultaneously during overnight polysmnography to understand the mechanisms of nocturnal oxygen desaturation and respiratory failure. The effect of bronchodilators on neural respiratory drive and sleep structure, in particular efficacy of neural respiratory drive will also be assessed. This project will lead to a better understanding of the pathophysiological change of COPD during sleep.

慢性阻塞性肺疾病（COPD）是一常见病，死亡率高。COPD患者气促、运动受限、呼吸衰竭的产生均与呼吸中枢驱动有关。长期以来，有关COPD患者特别是呼吸中枢驱动的研究主要在白天清醒状态下进行。然而COPD患者夜间死亡率显著大于白天；一些白天尚能维持正常通气的COPD 患者，睡眠状态下特别是快动眼睡眠期可出现血氧饱和度下降甚至呼吸衰竭。COPD患者常合并阻塞性睡眠呼吸暂停即重叠综合征，后者的发生发展除与上气道阻力增高有关外，也与呼吸中枢驱动有关。这一研究以膈肌肌电作为呼吸中枢驱动指标，同时检测上气道阻力变化，观察COPD包括重叠综合症患者夜间呼吸中枢驱动及其有效性、上气道阻力的变化以及支气管扩张剂对睡眠状态下COPD患者呼吸中枢驱动的影响，帮助阐明COPD 患者睡眠状态下的病理生理变化包括夜间通气下降及产生呼吸衰竭的机理，为合理治疗COPD包括重叠综合征提供新的思路。

我们记录50名单纯COPD患者与14名正常受试者睡眠状态下呼吸中枢驱动与通气量的变化，结果发现单纯COPD患者夜间通气量下降主要由呼吸驱动降低导致。为了探讨COPD患者合并OSA即重叠综合征患者夜间低通气与呼吸中枢驱动的关系，我们记录了16名重叠综合征患者睡眠状态下通气量与呼吸中枢驱动驱动的变化，并采用课题组建立的评价上气道阻力的新方法，膈肌肌电与气流的比值记录上气道阻力的变化。与单纯COPD患者不同，研究结果发现重叠综合征患者夜间低通气主要由上气道阻力增加所致。此外，重叠综合征患者的夜间低氧程度并不比单纯COPD患者更差。这一系列研究结果已发表于呼吸领域国际著名杂志，如美国呼吸道与危重症监护医学杂志与Thorax杂志，共发表三篇论著。