Department of Internal Medicine, National Hospital Organization Toneyama National Hospital, Toyonaka, Japan.
PLoS One. 2012;7(5):e35708. doi: 10.1371/journal.pone.0035708. Epub 2012 May 1.
Pulmonary cachexia is common in advanced chronic obstructive pulmonary disease (COPD), culminating in exercise intolerance and a poor prognosis. Ghrelin is a novel growth hormone (GH)-releasing peptide with GH-independent effects. The efficacy and safety of adding ghrelin to pulmonary rehabilitation (PR) in cachectic COPD patients were investigated.
METHODOLOGY/PRINCIPAL FINDINGS: In a multicenter, randomized, double-blind, placebo-controlled trial, 33 cachectic COPD patients were randomly assigned PR with intravenous ghrelin (2 µg/kg) or placebo twice daily for 3 weeks in hospital. The primary outcomes were changes in 6-min walk distance (6-MWD) and the St. George Respiratory Questionnaire (SGRQ) score. Secondary outcomes included changes in the Medical Research Council (MRC) scale, and respiratory muscle strength. At pre-treatment, serum GH levels were increased from baseline levels by a single dose of ghrelin (mean change, +46.5 ng/ml; between-group p<0.0001), the effect of which continued during the 3-week treatment. In the ghrelin group, the mean change from pre-treatment in 6-MWD was improved at Week 3 (+40 m, within-group p = 0.033) and was maintained at Week 7 (+47 m, within-group p = 0.017), although the difference between ghrelin and placebo was not significant. At Week 7, the mean changes in SGRQ symptoms (between-group p = 0.026), in MRC (between-group p = 0.030), and in maximal expiratory pressure (MEP; between-group p = 0.015) were better in the ghrelin group than in the placebo group. Additionally, repeated-measures analysis of variance (ANOVA) indicated significant time course effects of ghrelin versus placebo in SGRQ symptoms (p = 0.049) and MEP (p = 0.021). Ghrelin treatment was well tolerated.
CONCLUSIONS/SIGNIFICANCE: In cachectic COPD patients, with the safety profile, ghrelin administration provided improvements in symptoms and respiratory strength, despite the lack of a significant between-group difference in 6-MWD.
UMIN Clinical Trial Registry C000000061.
在晚期慢性阻塞性肺疾病（COPD）中，肺恶病质很常见，最终导致运动不耐受和预后不良。胃饥饿素是一种新型生长激素（GH）释放肽，具有 GH 独立的作用。本研究旨在探讨在恶病质 COPD 患者中添加胃饥饿素对肺康复（PR）的疗效和安全性。
方法/主要发现：在一项多中心、随机、双盲、安慰剂对照试验中，33 名恶病质 COPD 患者被随机分为两组，分别在医院内接受 PR 联合静脉内给予胃饥饿素（2μg/kg）或安慰剂，每日两次，共 3 周。主要终点是 6 分钟步行距离（6-MWD）和圣乔治呼吸问卷（SGRQ）评分的变化。次要终点包括英国医学研究理事会（MRC）量表和呼吸肌力量的变化。在治疗前，单次给予胃饥饿素后，血清 GH 水平从基线水平升高（平均变化，+46.5ng/ml；组间 p<0.0001），这种作用在 3 周的治疗期间持续存在。在胃饥饿素组中，治疗 3 周时，6-MWD 的平均变化较治疗前改善（+40m，组内 p=0.033），且在治疗 7 周时保持不变（+47m，组内 p=0.017），尽管胃饥饿素与安慰剂之间的差异无统计学意义。在治疗 7 周时，胃饥饿素组 SGRQ 症状（组间 p=0.026）、MRC（组间 p=0.030）和最大呼气压力（MEP；组间 p=0.015）的平均变化优于安慰剂组。此外，重复测量方差分析（ANOVA）表明，胃饥饿素与安慰剂相比，在 SGRQ 症状（p=0.049）和 MEP（p=0.021）方面有显著的时间进程效应。胃饥饿素治疗具有良好的耐受性。
结论/意义：在恶病质 COPD 患者中，尽管在 6-MWD 方面两组间无显著差异，但胃饥饿素治疗可改善症状和呼吸力量，且安全性良好。
UMIN 临床研究注册 C000000061。
