Walters Julia A E, Tan Daniel J, White Clinton J, Gibson Peter G, Wood-Baker Richard, Walters E Haydn
School of Medicine, University of Tasmania, MS1, 17 Liverpool Street, PO Box 23, Hobart, Tasmania, Australia, 7001.
Cochrane Database Syst Rev. 2014 Sep 1;2014(9):CD001288. doi: 10.1002/14651858.CD001288.pub4.
Acute exacerbations of chronic obstructive pulmonary disease (COPD) are a major cause of hospital admission and mortality. They contribute to long-term decline in lung function, physical capacity and quality of life. The most common causes are infective, and treatment includes antibiotics, bronchodilators and systemic corticosteroids as anti-inflammatory agents.
To assess the effects of corticosteroids administered orally or parenterally for treatment of acute exacerbations of COPD, and to compare the efficacy of parenteral versus oral administration.
We carried out searches using the Cochrane Airways Group Specialised Register of Trials, MEDLINE and CENTRAL (Cochrane Central Register of Controlled Trials), and checked references of included studies and trials registries. We conducted the last search in May 2014.
Randomised controlled trials comparing corticosteroids administered orally or parenterally with an appropriate placebo, or comparing oral corticosteroids with parenteral corticosteroids in the treatment of people with acute exacerbations of COPD. Other interventions (e.g. bronchodilators and antibiotics) were standardised for both groups. We excluded clinical studies of acute asthma.
We used standard methodological procedures expected by The Cochrane Collaboration.
Sixteen studies (n = 1787) met inclusion criteria for the comparison systemic corticosteroid versus placebo and 13 studies contributed data (n = 1620). Four studies (n = 298) met inclusion criteria for the comparison oral corticosteroid versus parenteral corticosteroid and three studies contributed data (n = 239). The mean age of participants with COPD was 68 years, median proportion of males 82% and mean forced expiratory volume in one second (FEV1) per cent predicted at study admission was 40% (6 studies; n = 633). We judged risk of selection, detection, attrition and reporting bias as low or unclear in all studies. We judged risk of performance bias high in one study comparing systemic corticosteroid with control and in two studies comparing intravenous corticosteroid versus oral corticosteroid.Systemic corticosteroids reduced the risk of treatment failure by over half compared with placebo in nine studies (n = 917) with median treatment duration 14 days, odds ratio (OR) 0.48 (95% confidence interval (CI) 0.35 to 0.67). The evidence was graded as high quality and it would have been necessary to treat nine people (95% CI 7 to 14) with systemic corticosteroids to avoid one treatment failure. There was moderate-quality evidence for a lower rate of relapse by one month for treatment with systemic corticosteroid in two studies (n = 415) (hazard ratio (HR) 0.78; 95% CI 0.63 to 0.97). Mortality up to 30 days was not reduced by treatment with systemic corticosteroid compared with control in 12 studies (n = 1319; OR 1.00; 95% CI 0.60 to 1.66).FEV1, measured up to 72 hours, showed significant treatment benefits (7 studies; n = 649; mean difference (MD) 140 mL; 95% CI 90 to 200); however, this benefit was not observed at later time points. The likelihood of adverse events increased with corticosteroid treatment (OR 2.33; 95% CI 1.59 to 3.43). Overall, one extra adverse effect occurred for every six people treated (95% CI 4 to 10). The risk of hyperglycaemia was significantly increased (OR 2.79; 95% CI 1.86 to 4.19). For general inpatient treatment, duration of hospitalisation was significantly shorter with corticosteroid treatment (MD -1.22 days; 95% CI -2.26 to -0.18), with no difference in length of stay the intensive care unit (ICU) setting.Comparison of parenteral versus oral treatment showed no significant difference in the primary outcomes of treatment failure, relapse or mortality or for any secondary outcomes. There was a significantly increased rate of hyperglycaemia in one study (OR 4.89; 95% CI 1.20 to 19.94).
AUTHORS' CONCLUSIONS: There is high-quality evidence to support treatment of exacerbations of COPD with systemic corticosteroid by the oral or parenteral route in reducing the likelihood of treatment failure and relapse by one month, shortening length of stay in hospital inpatients not requiring assisted ventilation in ICU and giving earlier improvement in lung function and symptoms. There is no evidence of benefit for parenteral treatment compared with oral treatment with corticosteroid on treatment failure, relapse or mortality. There is an increase in adverse drug effects with corticosteroid treatment, which is greater with parenteral administration compared with oral treatment.
慢性阻塞性肺疾病(COPD)急性加重是住院和死亡的主要原因。它们导致肺功能、身体能力和生活质量的长期下降。最常见的原因是感染性的,治疗包括使用抗生素、支气管扩张剂和全身用皮质类固醇作为抗炎药物。
评估口服或胃肠外给予皮质类固醇治疗COPD急性加重的效果,并比较胃肠外给药与口服给药的疗效。
我们使用Cochrane Airways Group专业试验注册库、MEDLINE和CENTRAL(Cochrane对照试验中心注册库)进行检索,并检查纳入研究的参考文献和试验注册库。我们于2014年5月进行了最后一次检索。
随机对照试验,比较口服或胃肠外给予皮质类固醇与适当的安慰剂,或比较口服皮质类固醇与胃肠外皮质类固醇治疗COPD急性加重患者。两组的其他干预措施(如支气管扩张剂和抗生素)均标准化。我们排除了急性哮喘的临床研究。
我们采用了Cochrane协作网预期的标准方法程序。
16项研究(n = 1787)符合全身用皮质类固醇与安慰剂比较的纳入标准,13项研究提供了数据(n = 1620)。4项研究(n = 298)符合口服皮质类固醇与胃肠外皮质类固醇比较的纳入标准,3项研究提供了数据(n = 239)。COPD参与者的平均年龄为68岁,男性中位数比例为82%,研究入组时预计的一秒用力呼气容积(FEV1)平均百分比为40%(6项研究;n = 633)。我们判断所有研究中选择、检测、失访和报告偏倚的风险为低或不明确。在一项比较全身用皮质类固醇与对照组的研究以及两项比较静脉用皮质类固醇与口服皮质类固醇的研究中,我们判断执行偏倚的风险为高。在9项治疗持续时间中位数为14天的研究(n = 917)中,与安慰剂相比,全身用皮质类固醇使治疗失败风险降低了一半以上,比值比(OR)为0.48(95%置信区间(CI)0.35至0.67)。证据质量被评为高质量,使用全身用皮质类固醇治疗9人(95%CI 7至14)可避免1例治疗失败。在两项研究(n = 415)中,有中等质量的证据表明,全身用皮质类固醇治疗一个月内复发率较低(风险比(HR)0.78;95%CI 0.63至0.97)。与对照组相比,12项研究(n = 1319;OR 1.00;95%CI 0.60至1.66)中全身用皮质类固醇治疗并未降低30天内的死亡率。在长达72小时的测量中,FEV1显示出显著的治疗益处(7项研究;n = 649;平均差(MD)140 mL;95%CI 90至200);然而,在后期时间点未观察到这种益处。皮质类固醇治疗会增加不良事件的可能性(OR 2.33;95%CI 1.59至3.43)。总体而言,每治疗6人就会多出现1例不良事件(95%CI 4至10)。高血糖风险显著增加(OR 2.79;95%CI 1.86至4.19)。对于一般住院治疗,皮质类固醇治疗可显著缩短住院时间(MD -1.22天;95%CI -2.26至-0.18),在重症监护病房(ICU)环境下住院时间无差异。胃肠外与口服治疗的比较显示,在治疗失败、复发或死亡率的主要结局以及任何次要结局方面均无显著差异。在一项研究中,高血糖发生率显著增加(OR 4.89;95%CI 1.20至19.94)。
有高质量证据支持通过口服或胃肠外途径使用全身用皮质类固醇治疗COPD加重,可降低治疗失败和一个月内复发的可能性,缩短不需要在ICU进行辅助通气的住院患者的住院时间,并使肺功能和症状更早改善。在治疗失败、复发或死亡率方面,没有证据表明胃肠外治疗与口服皮质类固醇治疗相比有优势。皮质类固醇治疗会增加药物不良反应,与口服治疗相比,胃肠外给药时不良反应更大。