Kopsaftis Zoe, Wood-Baker Richard, Poole Phillippa
Respiratory Medicine Unit, The Queen Elizabeth Hospital, Central Adelaide Local Health Network, Adelaide, Australia.
Cochrane Database Syst Rev. 2018 Jun 26;6(6):CD002733. doi: 10.1002/14651858.CD002733.pub3.
Influenza vaccinations are currently recommended in the care of people with COPD, but these recommendations are based largely on evidence from observational studies, with very few randomised controlled trials (RCTs) reported. Influenza infection causes excess morbidity and mortality in people with COPD, but there is also the potential for influenza vaccination to cause adverse effects, or not to be cost effective.
To determine whether influenza vaccination in people with COPD reduces respiratory illness, reduces mortality, is associated with excess adverse events, and is cost effective.
We searched the Cochrane Airways Trials Register, two clinical trials registries, and reference lists of articles. A number of drug companies we contacted also provided references. The latest search was carried out in December 2017.
RCTs that compared live or inactivated virus vaccines with placebo, either alone or with another vaccine, in people with COPD.
Two review authors independently extracted data. All entries were double-checked. We contacted study authors and drug companies for missing information. We used standard methods expected by Cochrane.
We included 11 RCTs with 6750 participants, but only six of these included people with COPD (2469 participants). The others were conducted on elderly and high-risk individuals, some of whom had chronic lung disease. Interventions compared with placebo were inactivated virus injections and live attenuated intranasal virus vaccines. Some studies compared intra-muscular inactivated vaccine and intranasal live attenuated vaccine with intra-muscular inactivated vaccine and intranasal placebo. Studies were conducted in the UK, USA and Thailand.Inactivated vaccine reduced the total number of exacerbations per vaccinated participant compared with those who received placebo (mean difference (MD) -0.37, 95% confidence interval (CI) -0.64 to -0.11; P = 0.006; two RCTs, 180 participants; low quality evidence). This was due to the reduction in 'late' exacerbations, occurring after three or four weeks (MD -0.39, 95% CI -0.61 to -0.18; P = 0.0004; two RCTs, 180 participants; low quality evidence). Both in people with COPD, and in older people (only a minority of whom had COPD), there were significantly more local adverse reactions in people who had received the vaccine, but the effects were generally mild and transient.There was no evidence of an effect of intranasal live attenuated virus when this was added to inactivated intramuscular vaccination.Two studies evaluating mortality for influenza vaccine versus placebo were too small to have detected any effect on mortality. However, a large study (N=2215) noted that there was no difference in mortality when adding live attenuated virus to inactivated virus vaccination, AUTHORS' CONCLUSIONS: It appeared, from the limited number of RCTs we were able to include, all of which were more than a decade old, that inactivated vaccine reduced exacerbations in people with COPD. The size of effect was similar to that seen in large observational studies, and was due to a reduction in exacerbations occurring three or more weeks after vaccination, and due to influenza. There was a mild increase in transient local adverse effects with vaccination, but no evidence of an increase in early exacerbations. Addition of live attenuated virus to the inactivated vaccine was not shown to confer additional benefit.
目前建议对慢性阻塞性肺疾病(COPD)患者进行流感疫苗接种,但这些建议主要基于观察性研究的证据,随机对照试验(RCT)报道极少。流感感染会导致COPD患者出现更多的发病和死亡情况,但流感疫苗接种也有可能产生不良反应,或者不具有成本效益。
确定COPD患者接种流感疫苗是否能减少呼吸道疾病、降低死亡率、是否会增加不良事件以及是否具有成本效益。
我们检索了Cochrane Airways试验注册库、两个临床试验注册库以及文章的参考文献列表。我们联系的多家制药公司也提供了参考文献。最近一次检索于2017年12月进行。
将活病毒或灭活病毒疫苗与安慰剂进行比较的随机对照试验,单独使用或与另一种疫苗联合使用,研究对象为COPD患者。
两位综述作者独立提取数据。所有条目都进行了双重检查。我们联系研究作者和制药公司获取缺失信息。我们采用Cochrane期望的标准方法。
我们纳入了11项随机对照试验,共6750名参与者,但其中只有6项纳入了COPD患者(2469名参与者)。其他试验是针对老年人和高危个体进行的,其中一些人患有慢性肺部疾病。与安慰剂相比的干预措施包括灭活病毒注射和减毒活鼻内病毒疫苗。一些研究比较了肌肉注射灭活疫苗和鼻内减毒活疫苗与肌肉注射灭活疫苗和鼻内安慰剂。研究在英国、美国和泰国进行。与接受安慰剂的参与者相比,灭活疫苗降低了每个接种参与者的总加重次数(平均差(MD)-0.37,95%置信区间(CI)-0.64至-0.11;P = 0.006;两项随机对照试验,180名参与者;低质量证据)。这是由于“晚期”加重次数的减少,即接种三或四周后发生的加重(MD -0.39,95% CI -0.61至-0.18;P = 0.0004;两项随机对照试验,180名参与者;低质量证据)。在COPD患者以及老年人(其中只有少数患有COPD)中,接种疫苗的人出现局部不良反应的情况明显更多,但这些影响通常较轻且为短暂性。当将减毒活鼻内病毒添加到肌肉注射灭活疫苗中时,没有证据表明有效果。两项评估流感疫苗与安慰剂死亡率的研究规模太小,无法检测到对死亡率的任何影响。然而,一项大型研究(N = 2215)指出,在灭活病毒疫苗接种中添加减毒活病毒时,死亡率没有差异。
从我们能够纳入的有限数量的随机对照试验来看,所有这些试验都有十多年的历史了,灭活疫苗似乎能减少COPD患者的加重情况。效果大小与大型观察性研究中所见相似,这是由于接种疫苗三周或更长时间后以及因流感导致的加重情况减少。接种疫苗后短暂的局部不良反应略有增加,但没有证据表明早期加重情况增加。在灭活疫苗中添加减毒活病毒并未显示出额外的益处。