单位：[1]National Center for Respiratory Diseases, State Key Laboratory of Respiratory Disease,Guangzhou Institute of Respiratory Diseases, the First Affiliated Hospital，Guangzhou Medical University,China[2]Third Affiliated Hospital, Guangzhou Medical University,China[3]Liwan Hospital, Guangzhou Medical University,China[4]Guangzhou Medical University, Guangzhou Panyu Center Hospital,China[5]First Affiliated Hospital, Sun Yat-sen University,China中山大学附属第一医院[6]First Affiliated Hospital of Jinan University,Guangzhou,China[7]Chenzhou No. 1 People’s Hospital, Chenzhou,China[8]Guizhou Provincial People’s Hospital, Guizhou,China[9]Wengyuan County People’s Hospital,China[10]Shaoguan Iron and Steel Group Company Limited Hospital,China[11]Shaoguan, Henan Provincial People’s Hospital, Zhengzhou,China[12]Affiliated Hospital of GuiYang Medical College, GuiYang,China[13]Second People’s Hospital of Hunan Province, Changsha,China[14]Huizhou First Hospital, Huizhou,China[15]Affiliated Zhongshan Hospital of Fudan University,China[16]Shanghai Xuhui Central Hospital, Shanghai,China[17]Shenzhen Sixth People’s Hospital, Shenzhen,China[18]First People’s Hospital of Foshan, Foshan,China[19]Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan,China华中科技大学同济医学院附属同济医院[20]Xinqiao Hospital, Chongqing,China[21]Affiliated Hospital, Guangdong Medical University,China[22]Second People’s Hospital of Zhanjiang, Zhanjiang,China[23]Beijing Chao-Yang Hospital, Beijing,China北京朝阳医院[24]Lianping County People’s Hospital, Heyuan ,China
BACKGROUND Patients with mild or moderate chronic obstructive pulmonary disease (COPD) rarely receive medications, because they have few symptoms. We hypothesized that long-term use of tiotropium would improve lung function and ameliorate the decline in lung function in patients with mild or moderate COPD. METHODS In a multicenter, randomized, double-blind, placebo-controlled trial that was conducted in China, we randomly assigned 841 patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1 (mild) or 2 (moderate) severity to receive a once-daily inhaled dose (18 mu g) of tiotropium (419 patients) or matching placebo (422) for 2 years. The primary end point was the between-group difference in the change from baseline to 24 months in the forced expiratory volume in 1 second (FEV 1) before bronchodilator use. Secondary end points included the between-group difference in the change from baseline to 24 months in the FEV 1 after bronchodilator use and the between-group difference in the annual decline in the FEV 1 before and after bronchodilator use from day 30 to month 24. RESULTS Of 841 patients who underwent randomization, 388 patients in the tiotropium group and 383 in the placebo group were included in the full analysis set. The FEV 1 in patients who received tiotropium was higher than in those who received placebo throughout the trial (ranges of mean differences, 127 to 169 ml before bronchodilator use and 71 to 133 ml after bronchodilator use; P<0.001 for all comparisons). There was no significant amelioration of the mean (+/- SE) annual decline in the FEV 1 before bronchodilator use: the decline was 38 +/- 6 ml per year in the tiotropium group and 53 +/- 6 ml per year in the placebo group (difference, 15 ml per year; 95% confidence interval [CI], -1 to 31; P = 0.06). In contrast, the annual decline in the FEV 1 after bronchodilator use was significantly less in the tiotropium group than in the placebo group (29 +/- 5 ml per year vs. 51 +/- 6 ml per year; difference, 22 ml per year [95% CI, 6 to 37]; P = 0.006). The incidence of adverse events was generally similar in the two groups. CONCLUSIONS Tiotropium resulted in a higher FEV 1 than placebo at 24 months and ameliorated the annual decline in the FEV 1 after bronchodilator use in patients with COPD of GOLD stage 1 or 2. (Funded by Boehringer Ingelheim and others; Tie-COPD ClinicalTrials.gov number, NCT01455129.)
基金：
Supported in part by an investigator-initiated study program by Boehringer Ingelheim and by grants from the National Key Technology Research and Development Program of the 12th and 13th National 5-Year Development Plan (2012BAI05B01 and 2016YFC1304101) and the Guangdong Provincial Science and Technology Research Department (2011B031800132).
第一作者单位：[1]National Center for Respiratory Diseases, State Key Laboratory of Respiratory Disease,Guangzhou Institute of Respiratory Diseases, the First Affiliated Hospital，Guangzhou Medical University,China
共同第一作者：
通讯作者：
通讯机构：[1]National Center for Respiratory Diseases, State Key Laboratory of Respiratory Disease,Guangzhou Institute of Respiratory Diseases, the First Affiliated Hospital，Guangzhou Medical University,China[*1]151 Yanjiang Xi Rd., 510120 Guangzhou City, Guangdong, China
推荐引用方式(GB/T 7714)：
Y. Zhou,N. Zhong,Xiaochen Li,et al.Tiotropium in Early-Stage Chronic Obstructive Pulmonary Disease[J].NEW ENGLAND JOURNAL OF MEDICINE.2017,377(10):923-935.doi:10.1056/NEJMoa1700228.
APA：
Y. Zhou,N. Zhong,Xiaochen Li,S. Chen,J. Zheng...&P. Ran.(2017).Tiotropium in Early-Stage Chronic Obstructive Pulmonary Disease.NEW ENGLAND JOURNAL OF MEDICINE,377,(10)
MLA：
Y. Zhou,et al."Tiotropium in Early-Stage Chronic Obstructive Pulmonary Disease".NEW ENGLAND JOURNAL OF MEDICINE 377..10(2017):923-935
医学