Wang Kay, Bettiol Silvana, Thompson Matthew J, Roberts Nia W, Perera Rafael, Heneghan Carl J, Harnden Anthony
Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Observatory Quarter, Woodstock Road, Oxford, Oxon, UK, OX2 6GG.
Cochrane Database Syst Rev. 2014 Sep 22;2014(9):CD003257. doi: 10.1002/14651858.CD003257.pub5.
Around 16 million cases of whooping cough (pertussis) occur worldwide each year, mostly in low-income countries. Much of the morbidity of whooping cough in children and adults is due to the effects of the paroxysmal cough. Cough treatments proposed include corticosteroids, beta2-adrenergic agonists, pertussis-specific immunoglobulin, antihistamines and possibly leukotriene receptor antagonists (LTRAs).
To assess the effectiveness and safety of interventions to reduce the severity of paroxysmal cough in whooping cough in children and adults.
We updated our searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2014, Issue 1), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, the Database of Abstracts of Reviews of Effects (DARE 2014, Issue 2), accessed from The Cochrane Library, MEDLINE (1950 to 30 January 2014), EMBASE (1980 to 30 January 2014), AMED (1985 to 30 January 2014), CINAHL (1980 to 30 January 2014) and LILACS (30 January 2014). We searched Current Controlled Trials to identify trials in progress.
We selected randomised controlled trials (RCTs) and quasi-RCTs of any intervention (excluding antibiotics and vaccines) to suppress the cough in whooping cough.
Two review authors (SB, MT) independently selected trials, extracted data and assessed the quality of each trial for this review in 2009. Two review authors (SB, KW) independently reviewed additional studies identified by the updated searches in 2012 and 2014. The primary outcome was frequency of paroxysms of coughing. Secondary outcomes were frequency of vomiting, frequency of whoop, frequency of cyanosis (turning blue), development of serious complications, mortality from any cause, side effects due to medication, admission to hospital and duration of hospital stay.
We included 12 trials of varying sample sizes (N = 9 to 135), mainly from high-income countries, including a total of 578 participants. Ten trials recruited children (N = 448 participants). Two trials recruited adolescents and adults (N = 130 participants). We considered only three trials to be of high methodological quality (one trial each of diphenhydramine, pertussis immunoglobulin and montelukast). Included studies did not show a statistically significant benefit for any of the interventions. Only six trials, including a total of 196 participants, reported data in sufficient detail for analysis. Diphenhydramine did not change coughing episodes; the mean difference (MD) of coughing spells per 24 hours was 1.9; 95% confidence interval (CI) -4.7 to 8.5 (N = 49 participants from one trial). One trial on pertussis immunoglobulin reported a possible mean reduction of -3.1 whoops per 24 hours (95% CI -6.2 to 0.02, N = 47 participants) but no change in hospital stay (MD -0.7 days; 95% CI -3.8 to 2.4, N = 46 participants). Dexamethasone did not show a clear decrease in length of hospital stay (MD -3.5 days; 95% CI -15.3 to 8.4, N = 11 participants from one trial) and salbutamol showed no change in coughing paroxysms per day (MD -0.2; 95% CI -4.1 to 3.7, N = 42 participants from two trials). Only one trial comparing pertussis immunoglobulin versus placebo (N = 47 participants) reported data on adverse events: 4.3% in the treatment group (rash) versus 5.3% in the placebo group (loose stools, pain and swelling at injection site).
AUTHORS' CONCLUSIONS: There is insufficient evidence to draw conclusions about the effectiveness of interventions for the cough in whooping cough. More high-quality trials are needed to assess the effectiveness of potential antitussive treatments in patients with whooping cough.
全球每年约有1600万例百日咳病例,主要发生在低收入国家。儿童和成人百日咳的大部分发病是由于阵发性咳嗽的影响。提出的咳嗽治疗方法包括皮质类固醇、β2肾上腺素能激动剂、百日咳特异性免疫球蛋白、抗组胺药以及可能的白三烯受体拮抗剂(LTRAs)。
评估减轻儿童和成人百日咳阵发性咳嗽严重程度的干预措施的有效性和安全性。
我们更新了对Cochrane对照试验中心注册库(CENTRAL,2014年第1期)的检索,其中包含Cochrane急性呼吸道感染小组的专业注册库、效果评价文摘数据库(DARE 2014年第2期),可从Cochrane图书馆获取,检索了MEDLINE(1950年至2014年1月30日)、EMBASE(1980年至2014年1月30日)、AMED(1985年至2014年1月30日)、CINAHL(1980年至2014年1月30日)和LILACS(2014年1月30日)。我们检索了“当前对照试验”以识别正在进行的试验。
我们选择了任何干预措施(不包括抗生素和疫苗)抑制百日咳咳嗽的随机对照试验(RCT)和半随机对照试验。
两位综述作者(SB,MT)在2009年独立选择试验、提取数据并评估每项试验的质量以用于本综述。两位综述作者(SB,KW)在2012年和2014年独立审查了更新检索中识别出的其他研究。主要结局是咳嗽发作的频率。次要结局是呕吐频率、哮吼声频率、发绀(变蓝)频率、严重并发症的发生、任何原因导致的死亡率、药物副作用、住院情况和住院时间。
我们纳入了12项样本量各异的试验(N = 9至135),主要来自高收入国家,共包括578名参与者。10项试验招募儿童(N = 448名参与者)。2项试验招募青少年和成人(N = 130名参与者)。我们仅认为3项试验方法学质量高(分别为苯海拉明、百日咳免疫球蛋白和孟鲁司特的一项试验)。纳入的研究未显示任何干预措施有统计学上的显著益处。只有6项试验,共196名参与者,报告的数据足够详细可用于分析。苯海拉明未改变咳嗽发作次数;每24小时咳嗽发作的平均差值(MD)为1.9;95%置信区间(CI)-4.7至8.5(来自一项试验的49名参与者)。一项关于百日咳免疫球蛋白的试验报告每24小时哮吼声可能平均减少-3.1次(95% CI -6.2至0.02,N = 47名参与者),但住院时间无变化(MD -0.7天;95% CI -3.8至2.4,N = 46名参与者)。地塞米松未显示住院时间明显缩短(MD -3.5天;95% CI -15.3至8.4,来自一项试验的11名参与者),沙丁胺醇未显示每日咳嗽发作次数有变化(MD -0.2;95% CI -4.1至3.7,来自两项试验的42名参与者)。只有一项比较百日咳免疫球蛋白与安慰剂的试验(N = 47名参与者)报告了不良事件数据:治疗组为4.3%(皮疹),安慰剂组为5.3%(腹泻、注射部位疼痛和肿胀)。
没有足够的证据就百日咳咳嗽干预措施的有效性得出结论。需要更多高质量试验来评估潜在镇咳治疗对百日咳患者的有效性。