口服茶碱对慢性阻塞性肺疾病稳定期患者疗效和安全性的Meta分析

目的 评价口服茶碱对慢性阻塞性肺疾病(COPD)稳定期患者的疗效和安全性.方法 在Medline、Embase、Web of Science、NIH Consensus Statements、Cochrane Central Register of Controlled Trials和中国生物医学文献数据库中检索1950至2009年间比较口服茶碱和安慰剂对COPD稳定期患者疗效或安全性的随机对照试验,对符合标准的文献进行Meta分析.对二分类资料使用相对危险度(RR)进行评估,对单位相同的连续性变量通过计算加权均数差值(WMD)和95%可信区间(CI)进行评估.结果 检索到的2010篇文献中有34篇文献(包括2087例患者)符合入选标准,口服茶碱组第1秒用力呼气容积、用力肺活量、最大呼气流速和动脉血氧分压均高于安慰剂组,WMD分别为0.09 L(95%CI为0.09～0.09,P<0.01)、0.14 L(95%CI为0.13～0.14,P<0.01)、17.0 L/min(95%CI,为6.9～27.2,P<0.01)、2.89 mm Hg(1 mm Hg=0.133 kPa,95%CI为1.11～4.66,P<0.01),动脉血二氧化碳分压低于安慰剂组,WMD为-2.05 mm Hg(95%CI为-3.59- -1.42,P<0.01),6 min步行距离长于安慰剂组,WMD为38.89 m(95%CI为21.55～56.22,P<0.01).口服茶碱组急性加重发生率为14.0%,安慰剂组为19.4%,合并RR为0.74(95%CI为0.59～0.93);口服茶碱组药物相关性不良反应发生率为22.1%,安慰剂组为8.7%,合并RR为2.54(95%CI为1.37～4.70);组间差异均有统计学意义(均P<0.01).结论 与安慰剂比较,口服茶碱治疗可以改善COPD稳定期患者的肺功能、动脉血氧分压和运动耐量,但药物相关性不良反应发生率较高.

Meta-analysis of efficacy and safety of oral theophylline in chronic obstructive pulmonary disease

Objective To evaluate the efficacy and safety of oral theophylline versus placebo in patients with stable chronic obstructive pulmonary disease (COPD). Methods The databases Medline,Embase, Web of Science, Cochrane Central Register of Controlled Trials and Chinese Biomedical Database were retrieved by using the key words " Uniphyl or Theophylline or Theo-Dur or theo or Theotrim or Elixophylline or Elixophyllin or PhyUocontin or aminophylline or Methylxanthine or nuelin or doxofylline"and "obstructive or bronchitis or pulmonary emphysema or bronchial hyperreactivity or COPD or COLD or emphysema" so as to search the materials about the randomized controlled clinical trials comparing the effectiveness of stable COPD treated by oral theophylline and placebo. A meta-analysis was conducted. For continuous variables, the results of individual studies were pooled using fixed-effect weighted mean difference (WMD) with a corresponding 95% confidence interval (CI). Where the results were expressed as dichotomous variables, the relative risk (RR) with 95% CI was calculated. Results Thirty-four documents about randomized controlled clinical trials, including a total of 2087 patients, from the retrieved 2010 documents accorded to the demand of enrollment. The results of meta-analysis showed that theophylline significantly improved the forced expiratory volume in 1 s, forced vital capacity and peak expiratory flow rate (WMD 0.09 L, 95%CI0. 09 -0.09; WMD0. 14 L, 95% CI0. 13 -0. 14; WMD 17.0 L/min and 95% CI 6. 9-27.2 respectively). Arterial oxygen tension and arterial carbon dioxide tension at rest both improved with treatment (WMD 2. 89 mm Hg, 95% CI 1.11 -4.66; WMD -2.05 mm Hg and 95%CI -3.59 to - 1.42 respectively). Six-minute walk distance significantly improved ( WMD 38. 89 meters, 95% CI 21.55- 56. 22) in treatment group. The RR of acute exacerbations was smaller between both groups ( RR 0. 74,95% CI0. 59-0.93). The RR of total adverse events was similar (RR 1.05, 95% CI 0.95 -1.16) while RR of drug-related adverse events was greater (RR 2. 54, 95% CI 1.37 -4. 70). And there was significant statistical difference. Conclusion Compared with the placebo, theophylline can improve lung function,arterial blood gas tensions and walking distance while the incidence of drug-related adverse events is higher.