Influenza vaccine for patients with chronic obstructive pulmonary disease

 

Abstract

Background

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 COPD patients but there is also the potential for influenza vaccination to cause adverse effects or not to be cost effective.

Objectives

To evaluate the evidence from RCTs for a treatment effect of influenza vaccination in COPD subjects. Outcomes of interest were exacerbation rates, hospitalisations, mortality, lung function and adverse effects.

Search methods

We searched the Cochrane Airways Group Specialised Register of trials, and reference lists of articles. References were also provided by a number of drug companies we contacted. The latest search was carried out in May 2010.

Selection criteria

RCTs that compared live or inactivated virus vaccines with placebo, either alone or with another vaccine in persons with COPD. Studies of people with asthma were excluded.

Data collection and analysis

Two reviewers extracted data. All entries were double checked. Study authors and drug companies were contacted for missing information.

Main results

Eleven trials were included but only six of these were specifically performed in COPD patients. The others were conducted on elderly and high-risk individuals, some of whom had chronic lung disease. Inactivated vaccine in COPD patients resulted in a significant reduction in the total number of exacerbations per vaccinated subject compared with those who received placebo (weighted mean difference (WMD) -0.37, 95% confidence interval -0.64 to -0.11, P = 0.006). This was due to the reduction in "late" exacerbations occurring after three or four weeks (WMD -0.39, 95% CI -0.61 to -0.18, P = 0.0004). In Howells 1961, the number of patients experiencing late exacerbations was also significantly less (odds ratio 0.13, 95% CI 0.04 to 0.45, P = 0.002). Both Howells 1961 and Wongsurakiat 2004 found that inactivated influenza vaccination reduced influenza -related respiratory infections (WMD 0.19, 95% CI 0.07 to 0.48, P = 0.0005). In both COPD patient and in elderly patients (only a minority of whom had COPD), there was a significant increase in the occurrence of local adverse reactions in vaccinees, 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. The studies are too small to have detected any effect on mortality.

An updated search conducted in September 2001did not yield any further studies. A search in 2003 yielded two further reports of the same eligible study Gorse 2003. A search in 2004 yielded two reports of the another eligible study Wongsurakiat 2004. The author informed us of another report of the same study Wongsurakiat 2004/2. An update search in May 2010 did not identify any new studies for consideration.

Authors' conclusions

It appears, from the limited number of studies performed, that inactivated vaccine reduces exacerbations in COPD patients. 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 is a mild increase in transient local adverse effects with vaccination, but no evidence of an increase in early exacerbations.

 

Plain language summary

Influenza vaccine for patients with chronic obstructive pulmonary disease

Despite the almost universal recommendation that people with chronic obstructive pulmonary disease (COPD) should receive an annual influenza vaccination, very few randomised controlled trials have evaluated the effect of influenza vaccination in these patients. This review looks at six studies in COPD patients and a further five in elderly or high risk patients, a proportion of whom had chronic lung disease. It shows that there is now some evidence from randomised trials that inactivated influenza vaccine indeed decreases "flare ups" of COPD, especially those that are related to the influenza virus itself. The inactivated influenza virus vaccine is given intramuscularly and is associated with an increase in local side effects such as pain at the site of injection. This is short-lived, not serious and is outweighed by the long term benefit of the vaccine. The inactivated virus vaccine does not cause influenza or any significant worsening of COPD.

 

摘要

背景

對慢性阻塞性肺病(COPD)患者施打流感疫苗

對於慢性阻塞性肺病患者的照顧，目前建議接種流感疫苗，但是這些建議主要是根據觀察性研究證據，很少來自於隨機對照試驗的報告。慢性阻塞性肺病患者一旦感染流行性感冒，將造成罹病率和死亡率增加；然而流感疫苗接種可能造成副作用，或不符合成本效益。

目標

有關慢性阻塞性肺病患者接受流感疫苗接種的效果，評估來自於隨機對照試驗的證據。重要結果有：發病率、住院率、死亡率、肺功能和副作用等。

搜尋策略

搜尋Cochrane Airways Group Specialised Register資料庫，以及文章的參考目錄清單。同時聯絡一些藥廠提供參考資料。最後一次搜尋時間是2007年5月。

選擇標準

在慢性阻塞性肺病患者身上，比較活性或去活性病毒疫苗和安慰劑的隨機對照試驗－單獨接種或與另一種疫苗同時接種。排除那些納入氣喘病患的研究。

資料收集與分析

兩位審查員擷取數據。所有輸入資料都經過雙重檢驗。短缺的資料則連絡研究作者和藥廠。

主要結論

共納入十一個試驗，但只有六個特別針對慢性阻塞性肺病患者。其他試驗對象為老年人和高危險群，其中有些是慢性阻塞性肺病患者。與安慰劑相比，慢性阻塞性肺病病患接受去活性疫苗者，其個人發作總次數明顯減少(加權平均差[WMD] 0.37，95% 信賴區間0.64到0.11，P = 0.006)。這是因為三到四週後的晚期發作減少(加權平均差0.39，95% 信賴區間0.61到0.18，P = 0.0004)。Howells氏1961年的 報告，經驗晚期發作的病人數也明顯減少(危險對比值 [OR] 0.13，95%信賴區間0.04到0.45，P = 0.002)。Howells氏在1961年和Wongsurakiat氏於2004年的報告都發現：去活性流感疫苗接種可以減少流感相關的呼吸道感染(加權平均差0.19，95% 信賴區間0.07到0.48，P = 0.0005)。在慢性阻塞性肺病病患和老年病患(只有一小部分有慢性阻塞性肺病)中，注射疫苗的局部不良反應明顯增加，但通常是輕度和暫時性的。沒有證據顯示：在去活性肌肉注射疫苗外，加上鼻內減毒活性病毒的效果；這些研究太小以至於無法偵測到對死亡率的影響。2001年9月的更新搜尋並沒有找到任何進一步的研究。2003 年的搜尋找到新的研究－Gorse氏2003年的兩篇報告。2004年的搜尋又找到Wongsurakiat氏2004年研究的兩篇報告。該作者通知我們同一個還有另一篇報告Wongsurakiat 2004/2。2006年5月再一次搜尋，就沒有找到任何值得參考的新研究。

作者結論

這些數量有限的研究似乎顯示：去活性流感疫苗可以減少慢性阻塞性肺病患者的發作頻率。有效程度與大型觀察性研究結果相當，主要是因為疫苗接種三週及以後的發作減少。疫苗接種後的暫時性局部副作用稍有增加，但沒有增加早期發作的證據。

翻譯人

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

雖然幾乎一致建議，慢性阻塞性肺病患者應每年接種流感疫苗，但是，評估流感疫苗在這些患者的效果的隨機對照試驗卻很少。本回顧討論六篇針對慢性阻塞性肺病的研究，另外五篇針對老人或高危險群(部份有慢性肺病)的研究。目前有一些來自於隨機對照試驗的證據顯示：去活性流感疫苗的確可以減少慢性阻塞性肺病的發作，尤其是那些和流感病毒本身有關的發作。去活性流感疫苗經由肌肉注射，因此與注射部位疼痛等局部副作用有關，但這是短暫、不嚴重的，疫苗的長期效益遠遠超越此一反應。去活性病毒疫苗不會造成流行性感冒，也不會造成慢性阻塞性肺病的明顯惡化。