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噻托溴铵治疗早期慢性阻塞性肺疾病
Tiotropium in Early-Stage Chronic Obstructive Pulmonary Disease


Yumin Zhou ... 呼吸系统疾病 • 2017.09.07
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噻托溴铵显著缓解早期慢性阻塞性肺疾病肺功能下降

 

陈亚红

北京大学第三医院呼吸与危重症医学科

 

中国慢性阻塞性肺疾病(慢阻肺)早期诊断率低,初诊为慢阻肺中重度者超过60%,所有被诊断为慢阻肺的患者中,仅35.1%的患者以往被诊断为慢阻肺1。人群流行病学研究发现,《慢性阻塞性肺疾病全球倡议》(GOLD)1级和2级患者比例超过70%,这些患者没有明显的活动受限和呼吸困难,很少接受药物治疗,只有当疾病明显进展后才到医院就诊。GOLD 2017提出慢阻肺的治疗目标包括短期目标(改善症状、活动耐力和生活质量)和长期目标(延缓疾病进展速率、减少急性加重频率、降低病死率)2,目前的慢阻肺治疗药物临床试验较少关注GOLD 1级或CAT评分<10分的患者,即使少数对其关注的研究也仅是进行事后分析。因此,早期慢阻肺存在被忽略的现象。慢阻肺的诊断和治疗前移是将来慢阻肺防控的突破。

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摘要


背景

轻度或中度慢性阻塞性肺疾病(COPD)患者因为症状较少而很少接受药物治疗。我们的研究假设轻或中度COPD患者长期使用噻托溴铵会改善肺功能,并改善肺功能下降。

 

方法

在中国开展的一项多中心、随机、双盲、安慰剂对照临床试验中,我们随机分配841例《慢性阻塞性肺疾病全球倡议》(GOLD)1级(轻度)或2级(中度)COPD患者分别接受每日1次吸入给药的(18 μg)噻托溴铵(419例患者)或匹配安慰剂(422例患者)治疗达2年。研究主要终点是基线至24个月吸入支气管扩张剂前第一秒用力呼气量(FEV1)变化的组间差异。次要终点包括基线至24个月吸入支气管扩张剂后FEV1变化的组间差异、第30日至24个月吸入支气管扩张剂前FEV1年度降幅的组间差异和吸入后FEV1年度降幅的组间差异。

 

结果

在随机分配的841例患者中,噻托溴铵组388例患者和安慰剂组383例患者进入全分析集。整个临床试验中,噻托溴铵组患者FEV1均高于安慰剂组患者(均值差范围,吸入支气管扩张剂前为127~169 mL,而吸入支气管扩张剂后为71~133 mL,所有比较P<0.001)。吸入支气管扩张剂前FEV1年度降幅均值(±SE)未出现显著改善:噻托溴铵组降幅为每年38 mL±6 mL,而安慰剂组降幅为每年53 mL±6 mL(差值为每年15 mL;95%置信区间[CI],-1~31;P=0.06)。相比之下,噻托溴铵组吸入支气管扩张剂后年度降幅比安慰剂组显著较小(每年29 mL±5 mL vs.每年51 mL±6 mL;差值为每年22 mL [95% CI,6~37];P=0.006)。两组不良事件发生率基本相似。

 

结论

GOLD 1级或2级COPD患者中,与安慰剂相比,噻托溴铵提高了24个月时的FEV1,同时改善了吸入支气管扩张剂后FEV1的年度降幅(勃林格殷格翰公司等资助;Tie-COPD在ClinicalTrials.gov注册号为NCT01455129)。





作者信息

Yumin Zhou, M.D., Ph.D., Nan-shan Zhong, Ph.D., Xiaochen Li, M.D., Shuyun Chen, M.D., Jinping Zheng, M.D., Dongxing Zhao, M.D., Weimin Yao, M.D., Rongchang Zhi, M.D., Liping Wei, M.D., Bingwen He, M.D., Xiangyan Zhang, M.D., Changli Yang, M.D., Ying Li, M.D., Fenglei Li, M.D., Juan Du, M.D., Jianping Gui, M.D., Bin Hu, M.D., Chunxue Bai, M.D., Ping Huang, M.D., Gang Chen, M.D., Yongjian Xu, M.D., Changzheng Wang, M.D., Biao Liang, M.D., Yinhuan Li, M.D., Guoping Hu, M.D., Hui Tan, M.D., Xianwei Ye, M.D., Xitao Ma, M.D., Yan Chen, M.D., Xiwei Hu, M.D., Jia Tian, M.D., Xiaodan Zhu, M.D., Zhe Shi, M.D., Xiufang Du, M.D., Minjing Li, M.D., Shengming Liu, M.D., Ronghuan Yu, M.D., Jianping Zhao, M.D., Qianli Ma, M.D., Canmao Xie, M.D., Xiongbin Li, M.D., Tao Chen, M.D., Yingxiang Lin, M.D., Lizhen Zeng, M.D., Changxiu Ye, M.D., Weishu Ye, M.D., Xiangwen Luo, M.D., Lingshan Zeng, M.D., Shuqing Yu, M.D., Wei-jie Guan, Ph.D., and Pixin Ran, Ph.D.
From the National Center for Respiratory Diseases, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Diseases, the First Affiliated Hospital (Y.Z., N.Z., Xiaochen Li, S.C., J. Zheng, D.Z., W.G., P.R.), the Third Affiliated Hospital (L.W., G.H.), and Liwan Hospital (F.L., Y.C.), Guangzhou Medical University, Guangzhou Panyu Center Hospital (R.Z., Yinhuan Li), the First Affiliated Hospital, Sun Yat-sen University (C.X.), and the First Affiliated Hospital of Jinan University (S.L.), Guangzhou, Chenzhou No. 1 People’s Hospital, Chenzhou (B. He, H.T.), Guizhou Provincial People’s Hospital, Guizhou (X. Zhang, X.Y.), Wengyuan County People’s Hospital (C. Yang, Lizhen Zeng, C. Ye) and Shaoguan Iron and Steel Group Company Limited Hospital (T.C.), Shaoguan, Henan Provincial People’s Hospital, Zhengzhou (Ying Li, X.M.), the Affiliated Hospital of GuiYang Medical College, GuiYang (J.D., X.H.), the Second People’s Hospital of Hunan Province, Changsha (J.G., J.T.), Huizhou First Hospital, Huizhou (B. Hu, Z.S.), Affiliated Zhongshan Hospital of Fudan University (C.B., X. Zhu) and Shanghai Xuhui Central Hospital (R.Y.), Shanghai, Shenzhen Sixth People’s Hospital, Shenzhen (P.H., X.D.), the First People’s Hospital of Foshan, Foshan (G.C., M.L.), Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan (Y.X., J. Zhao), Xinqiao Hospital, Chongqing (C.W., Q.M.), the Affiliated Hospital, Guangdong Medical University (W. Yao, B.L.), and the Second People’s Hospital of Zhanjiang (Xiongbin Li), Zhanjiang, Beijing Chao-Yang Hospital, Beijing (Y. Lin), and Lianping County People’s Hospital, Heyuan (W. Ye, X. Luo, Lingshan Zeng, S.Y.) — all in China. Address reprint requests to Dr. Ran at 151 Yanjiang Xi Rd., 510120 Guangzhou City, Guangdong, China, or at pxran@gzhmu.edu.cn. A complete list of the investigators in the Tiotropium in Early Chronic Obstructive Pulmonary Disease Patients in China (Tie-COPD) trial is provided in the Supplementary Appendix, available at NEJM.org.

 

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