目的：系统评价茶碱联合噻托溴铵对稳定期慢性阻塞性肺疾病（COPD）患者肺功能及相关指标的影响，为临床提供循证参考。方法：计算机检索Cochrane图书馆、PubMed、EMBase、中国生物医学文献数据库、 CNKI、维普数据库和万方数字化期刊全文数据库中关于茶碱联合噻托溴铵治疗稳定期COPD患者的随机对照 试验（RCT），根据纳入与排除标准进行筛选，提取资料后按照改良的Jadad 评分表评价文献质量，并采用 RevMan 5.2统计软件对相关指标进行统计分析。结果：共纳入20项RCT，合计1496例患者。Meta分析结果显 示, 茶碱与噻托溴铵联用可明显提升患者的第1秒用力呼气容积（FEV1）[SMD＝0.52，95%CI（0.33，0.71），P < 0.001]、第1秒用力呼气容积占预计值百分比（preFEV1%）[MD＝5.05，95%CI（3.86，6.24），P < 0.001]、第1秒用力 呼气容积与用力肺活量的比值（FEV1/FVC）[SMD = 0.70，95%CI(0.34，1.05），P < 0.001]、用力肺活量（FVC） [MD = 0.21，95%CI（0.14,0.29），P < 0.001]、深吸气量(IC）[MD = 0.33，95%CI（0.23，0.42），P < 0.001]，明显降低患 者的圣乔治呼吸问卷评分（SGRQ）[SMD = -0.96，95%CI（-1.35，-0.58），P < 0.001]、mMRC评分[MD = -0.66，95% CI（-0.87，-0.44），P < 0.001]，差异均具有统计学意义；试验组6 min步行试验距离（6WMD）[SMD = 0.68，95%CI （-0.24，1.60），P = 0.15]与再次入院时间[MD = -0.10，95%CI（-0.38，0.18），P = 0.48]以及急性加重次数[SMD = - 0.36，95%CI（-0.74，0.02），P = 0.06]与对照组相比，差异均无统计学意义。结论：茶碱与噻托溴铵联用可改善稳 定期COPD患者肺功能，减轻呼吸困难症状，且未增加不良反应发生率。

Objective: To systematically evaluate the effect of theophylline plus tiotropium on lung function and related parameters in patients with stable chronic obstructive pulmonary disease (COPD), and provide evidence-based reference for clinical. Methods: Retrieved from Cochrane Library, PubMed, EMBase, CBM, CNKI, VIP and WanFang Database, randomized controlled trials (RCTs) of theophylline plus tiotropium in the treatment of patients with stable COPD were collected. RCTs were screened according to the inclusion and exclusion criteria after the data was extracted, and the quality of the included studies were evaluated with modified Jadad scale. Then, meta-analysis was performed by using RevMan 5.2 software. Results: Totally 20 RCTs were included, involving 1496 patients. Meta-analysis showed that the theophylline plus tiotropium significantly increased FEV1 [SMD = 0.52, 95%CI(0.33, 0.71), P < 0.001], preFEV1% [MD = 5.05, 95%CI(3.86, 6.24), P < 0.001], FEV1/FVC [SMD = 0.70, 95%CI (0.34, 1.05), P < 0.001], FVC [MD = 0.21, 95% CI (0.14, 0.29), P < 0.001], and IC [MD = 0.33, 95%CI(0.23, 0.42), P < 0.001] in patients, significantly reduced SGRQ [SMD = -0.96, 95%CI(-1.35, -0.58), P < 0.001], mMRC scores [MD = -0.66, 95%CI(-0.87, -0.44), P < 0.001], with statistical significance. The 6-minute walk distance (6MWD) [SMD = 0.68, 95%CI(-0.24, 1.60), P = 0.15], readmission time [MD = -0.1095%CI(-0.38, 0.18), P = 0.48] and the number of acute exacerbations [SMD = -0.36, 95%CI(-0.74, 0.02), P = 0.06] showed no statistically significant difference between trail group and control group. Conclusion: Theophylline plus tiotropium can improve the lung function of patients with stable COPD and alleviate the symptoms of dyspnea without increasing the incidence of adverse reactions.

国家自然科学基金委青年基金项目（81402991）：基于AC酶靶点筛选云南特色药用植物毛喉鞘蕊花中抗COPD活性成分，负责人：翁稚颖；云 南省科技厅国际合作重点项目（2014IA033）：药物高效筛选新技术的引进和应用,负责人：翁稚颖；云南省科技厅应用基础重点项目 （2017FA043)：异佛司可林拮抗COPD药理作用分子机制研究,负责人：杨为民；云南省科技厅重点新产品研发项目（2014BC012)：治疗慢性阻塞 性肺病化学I类新药异佛司可林片临床前研究,负责人：杨为民。