Drummond M Bradley, Dasenbrook Elliott C, Pitz Marshall W, Murphy David J, Fan Eddy
Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD 21287, USA.
JAMA. 2008 Nov 26;300(20):2407-16. doi: 10.1001/jama.2008.717.
Recent studies of inhaled corticosteroid (ICS) therapy for managing stable chronic obstructive pulmonary disease (COPD) have yielded conflicting results regarding survival and risk of adverse events.
To systematically review and quantitatively synthesize the effects of ICS therapy on mortality and adverse events in patients with stable COPD.
Search of MEDLINE, CENTRAL, EMBASE, CINAHL, Web of Science, and PsychInfo through February 9, 2008.
Eligible studies were double-blind, randomized controlled trials comparing ICS therapy for 6 or more months with nonsteroid inhaled therapy in patients with COPD.
Two authors independently abstracted data including study characteristics, all-cause mortality, pneumonia, and bone fractures. The I(2) statistic was used to assess heterogeneity. Study-level data were pooled using a random-effects model (when I(2) > or = 50%) or a fixed-effects model (when I(2) < 50%). For the primary outcome of all-cause mortality at 1 year, our meta-analysis was powered to detect a 1.0% absolute difference in mortality, assuming a 2-sided alpha of .05 and power of 0.80.
Eleven eligible randomized controlled trials (14,426 participants) were included. In trials with mortality data, no difference was observed in 1-year all-cause mortality (128 deaths among 4636 patients in the treatment group and 148 deaths among 4597 patients in the control group; relative risk [RR], 0.86; 95% confidence interval [CI], 0.68-1.09; P = .20; I(2) = 0%). In the trials with data on pneumonia, ICS therapy was associated with a significantly higher incidence of pneumonia (777 cases among 5405 patients in the treatment group and 561 cases among 5371 patients in the control group; RR, 1.34; 95% CI, 1.03-1.75; P = .03; I(2) = 72%). Subgroup analyses indicated an increased risk of pneumonia in the following subgroups: highest ICS dose (RR, 1.46; 95% CI, 1.10-1.92; P = .008; I(2) = 78%), shorter duration of ICS use (RR, 2.12; 95% CI, 1.47-3.05; P < .001; I(2) = 0%), lowest baseline forced expiratory volume in the first second of expiration (RR, 1.90; 95% CI, 1.26-2.85; P = .002; I(2) = 0%), and combined ICS and bronchodilator therapy (RR, 1.57; 95% CI, 1.35-1.82; P < .001; I(2) = 24%).
Among patients with COPD, ICS therapy does not affect 1-year all-cause mortality. ICS therapy is associated with a higher risk of pneumonia. Future studies should determine whether specific subsets of patients with COPD benefit from ICS therapy.
近期关于吸入性糖皮质激素（ICS）治疗稳定期慢性阻塞性肺疾病（COPD）的研究在生存率和不良事件风险方面得出了相互矛盾的结果。
系统评价并定量综合ICS治疗对稳定期COPD患者死亡率和不良事件的影响。
检索截至2008年2月9日的MEDLINE、CENTRAL、EMBASE、CINAHL、Web of Science和PsychInfo。
符合条件的研究为双盲随机对照试验，比较COPD患者接受6个月或更长时间的ICS治疗与非类固醇吸入治疗。
两位作者独立提取数据，包括研究特征、全因死亡率、肺炎和骨折情况。使用I²统计量评估异质性。采用随机效应模型（当I²≥50%时）或固定效应模型（当I²<50%时）汇总研究水平的数据。对于1年全因死亡率这一主要结局，我们的荟萃分析旨在检测死亡率1.0%的绝对差异，假设双侧α为0.05，检验效能为0.80。
纳入了11项符合条件的随机对照试验（14426名参与者）。在有死亡率数据的试验中，1年全因死亡率未观察到差异（治疗组4636例患者中有128例死亡，对照组4597例患者中有148例死亡；相对危险度[RR]，0.86；95%置信区间[CI]，0.68 - 1.09；P = 0.20；I² = 0%）。在有肺炎数据的试验中，ICS治疗与肺炎发生率显著升高相关（治疗组5405例患者中有777例，对照组5371例患者中有561例；RR，1.34；95% CI，1.03 - 1.75；P = 0.03；I² = 72%）。亚组分析表明，在以下亚组中肺炎风险增加：ICS最高剂量组（RR，1.46；95% CI，1.10 - 1.92；P = 0.008；I² = 78%）、ICS使用时间较短组（RR，2.12；95% CI，1.47 - 3.05；P < 0.001；I² = 0%）、第一秒用力呼气容积基线最低组（RR，1.90；95% CI，1.26 - 2.85；P = 0.002；I² = 0%）以及ICS与支气管扩张剂联合治疗组（RR，1.57；95% CI，1.35 - 1.82；P < 0.001；I² = 24%）。
在COPD患者中，ICS治疗不影响1年全因死亡率。ICS治疗与肺炎风险较高相关。未来研究应确定COPD患者的特定亚组是否从ICS治疗中获益。
