Bishop Clark, Hudson Valerie M, Hilton Sterling C, Wilde Cathleen
Utah Valley Regional Medical Center, Provo, UT, USA.
Chest. 2005 Jan;127(1):308-17. doi: 10.1378/chest.127.1.308.
To assess the impact of inhaled, buffered reduced glutathione (GSH) on clinical indicators of cystic fibrosis (CF) pathophysiology.
A randomized, double-blind, placebo-controlled pilot study was conducted over an 8-week period. Nineteen subjects, age 6 to 19 years, with CF status documented by positive sweat chloride test results (> 60 mEq/L) were recruited for the trial. After matching on age and sex, 10 patients were randomly assigned to the treatment group and 9 patients to the placebo group. Primary outcomes were FEV1, FVC, forced expiratory flow at 25 to 75% of vital capacity, and peak flow; secondary outcomes were body mass index, 6-min walk distance, and self-reported cough frequency, mucus production/viscosity/color, wellness, improvement, and stamina. INTERVENTIONS AND ANALYSIS: Treatment was buffered GSH, and placebo was sodium chloride with a hint of quinine. The total daily dose of buffered GSH was approximately 66 mg/kg of body weight, and the total daily dose of placebo was approximately 15 mg/kg of body weight (quinine, 25 to 30 microg/kg). Doses were distributed across four inhalation sessions per day and spaced 3- to 4-h apart. General linear mixed models were used to analyze the data. The final sample size was nine subjects in the treatment group and seven subjects in the placebo group.
Mean change for peak flow was -6.5 L/min for the placebo group and +33.7 L/min for the GSH group (p = 0.04), and self-reported average improvement on a scale from 1 to 5 (1 being much worse and 5 being much better) was 2.8 for placebo and 4.7 for GSH (p = 0.004). Of the 13 primary and secondary outcomes examined, 11 outcomes favored the treatment group over the placebo group (p = 0.002), indicating a general tendency of improvement in the GSH group. No adverse events in the treatment group were noted.
This pilot study indicates the promise of nebulized buffered GSH to ameliorate CF disease, and longer, larger, and improved studies of inhaled GSH are warranted.
评估吸入性缓冲还原型谷胱甘肽（GSH）对囊性纤维化（CF）病理生理学临床指标的影响。
进行了一项为期8周的随机、双盲、安慰剂对照的试点研究。招募了19名年龄在6至19岁之间、汗液氯化物试验结果阳性（>60 mEq/L）证明患有CF的受试者参与试验。在按年龄和性别匹配后，10名患者被随机分配到治疗组，9名患者被分配到安慰剂组。主要结局指标为第一秒用力呼气容积（FEV1）、用力肺活量（FVC）、肺活量25%至75%时的用力呼气流量以及峰值流速；次要结局指标为体重指数、6分钟步行距离以及自我报告的咳嗽频率、痰液产生/黏稠度/颜色、健康状况、改善情况和耐力。
治疗药物为缓冲型GSH，安慰剂为含微量奎宁的氯化钠。缓冲型GSH的每日总剂量约为66 mg/kg体重，安慰剂的每日总剂量约为15 mg/kg体重（奎宁，25至30 μg/kg）。剂量分布在每天4次吸入疗程中，每次间隔3至4小时。使用一般线性混合模型分析数据。最终样本量为治疗组9名受试者，安慰剂组7名受试者。
安慰剂组峰值流速的平均变化为-6.5 L/分钟，GSH组为+33.7 L/分钟（p = 0.04），自我报告的1至5分评分（1分为差得多，5分为好得多）的平均改善情况，安慰剂组为2.8，GSH组为4.7（p = 0.004）。在检查的13项主要和次要结局指标中，11项指标治疗组优于安慰剂组（p = 0.002），表明GSH组总体有改善趋势。治疗组未观察到不良事件。
这项试点研究表明雾化缓冲型GSH有望改善CF疾病，有必要对吸入性GSH进行更长时间、更大规模和改进后的研究。
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