Anticholinergic agents for chronic asthma in adults

 

Abstract

Background

Anticholinergic agents such as ipratropium bromide are sometimes used in the treatment of chronic asthma. They effect bronchodilation and have also been used in combination with ß2 -agonists in the management of chronic asthma.

Objectives

To examine the effectiveness of anticholinergic agents versus placebo and in comparison with ß2 -agonists or as adjunctive therapy to ß2 -agonists.

Search methods

The Cochrane Airways Group asthma and wheeze database was searched with a pre-defined search strategy. Searches were current as of August 2008. Reference lists of articles were also examined.

Selection criteria

Randomised trials or quasi-randomised trials were considered for inclusion. Studies assessing an anticholinergic agent versus placebo or in combination/comparison with ß2 -agonists were included. In practice, all ß2 -agonists were short acting. Short-term (less than 24 hours duration) were not considered for this review.

Data collection and analysis

Two reviewers independently assessed abstracts for retrieval of full text articles. Papers were then assessed for suitability for inclusion in the review. Data from included studies were extracted by two reviewers and entered into the software package (RevMan 4.2). We contacted authors for missing data and some responded. Adverse effect data were analysed if reported in the included studies.

Main results

The studies analysed were in two groups: those comparing anticholinergics with placebo and those comparing the combination of anticholinergics with short acting ß2 -agonists versus short acting ß2 -agonists alone. The former group had 13 studies involving 205 participants included in this review, and the latter 9 studies involving 440 patients. Generally methodological quality was poorly reported, and there were some reservations with respect to the quality of the studies. Despite the limited number of studies that could be combined, anticholinergic agents in comparison with placebo resulted in more favourable symptom scores particularly in respect of daytime dyspnoea (WMD -0.09 (95%CI -0.14, -0.04, 3 studies, 59 patients). Daily peak flow measurements also showed a statistically significant improvement for the anticholinergic (e.g. morning PEF: WMD =14.38 litres/min (95%CI 7.69, 21.08; 3 studies, 59 patients). However the clinical significance is small and in terms of peak flow measurements equates to approximately a 7% increase over placebo. The more clinically relevant comparison of a combination of anticholinergic plus short acting ß2 -agonist versus short acting ß2 -agonist alone gave no evidence in respect of symptom scores or peak flow rates of any significant differences between the two regimes. Again there are reservations with respect to the quality of the information from which these conclusions are drawn. An update search in August 2004 did not identify any new studies.

Authors' conclusions

Overall this review provides no justification for routinely introducing anticholinergics as part of add-on treatment for patients whose asthma is not well controlled on standard therapies. This does not exclude the possibility that there may be a sub-group of patients who derive some benefit and a trial of treatment in individual patients may still be justified. The role of long term anticholinergics such as tiotropium bromide has yet to be established in patients with asthma and any future trials might draw on the messages derived from this review.

 

Plain language summary

Anticholinergic agents for chronic asthma in adults

Anticholinergic agents such as Atrovent are sometimes used to treat people with asthma as a bronchodilator that opens up the airways in the lungs. This review found that although this treatment was better than placebo, the size of the effect was rather small. When the drug was used in combination with more widely used bronchodilators (beta-agonists such as fenoterol), it did not appear to add much benefit. However, there are concerns about the quality of the studies that have been analysed. It could be that there are some adults with chronic asthma who respond to treatment with anticholinergic drugs, but the review has not been able to identify their common characteristics.

 

摘要

背景

以抗膽鹼藥物治療成人慢性氣喘

抗膽鹼藥物(anticholinergic agents)如ipratropium bromide有時會被用於治療慢性氣喘。這些藥物具有擴張支氣管的效力，亦曾合併2促效劑用於治療慢性氣喘。

目標

評估抗膽鹼藥物相較於安慰劑及2促效劑的療效，以及作為2促效劑的輔助治療的效果。

搜尋策略

我們依據預先訂妥的策略來搜尋Cochrane Airways Group Asthma and Wheeze Database。搜尋日期至2004年8月。相關論文之參考文獻亦作檢視。

選擇標準

相關之隨機或半隨機試驗均考慮納入。凡評估抗膽鹼藥物與安慰劑或2促效劑比較，以及與2促效劑合併治療的研究均予納入。實際上所有2促效劑均屬短效。而研究則分為短程(小於24小時)及長程，本回顧乃報導後者，前者則在另一篇回顧「以抗膽鹼藥物短程治療成人慢性氣喘」。

資料收集與分析

兩位評論者獨立評估文獻摘要以確認要蒐集哪些論文的全文。然後再評估哪些論文適於納入回顧中。被納入論文的數據由兩位評論者選取並輸入套裝軟體中(RevMan 4.2)。我們聯繫數據有漏失的研究之作者而獲得一些回應。納入的研究中所有報告的不良效應數據亦予以分析。

主要結論

相關研究分為兩組：比較抗膽鹼藥物與安慰劑，以及比較抗膽鹼藥物合併使用短效2促效劑與單獨使用短效2促效劑。在本回顧中，前一組有13項研究涉及205名參與者，後一組有9項研究涉及440名參與者。大體上這些研究在方法學的陳述不佳，而研究品質亦有一些有待商榷之處。儘管這些有限的研究可以合併分析，與安慰劑相較，抗膽鹼藥物有較佳的症狀評分，特別是日間呼吸困難(權重平均差﹝WMD﹞：−0.09；95% CI：−0.14 – −0.04，3項研，59名病人)。日常頂峰流量測量在抗膽鹼藥物組亦呈現統計學有意義的改善(如早上的PEF：WMD = 14.38 L/分鐘；95% CI：7.69 – 21.08，3項研，59名病人)。然而其臨床意義不大，如頂峰流量測量的改善優於安慰劑的程度約僅有7%。較與臨床相關的試驗是比較合併抗膽鹼藥物及短效2促效劑與單獨使用短效2促效劑之效益，但沒有證據顯示這兩種治療在症狀評分及頂峰流量等並無顯著差異。再次提醒的是由於資料品質有問題，故要由此下結論仍有所保留。在2004年8月的更新搜尋並未找到新的研究。

作者結論

整體而言本回顧並未對以標準治療無良好控制的氣喘病人是否應常規附加使用抗膽鹼藥物的議題提供支持證據。但這並非排除其可能性，或許會有某一子群(subgroup)的病人會獲得效益，故須對獨特的病人進行試驗。氣喘病人長期使用抗膽鹼藥物如tiotropium bromide仍未有定論，本回顧將持續把未來的試驗引入分析。

翻譯人

本摘要由中國醫藥大學附設醫院陳祖裕翻譯。

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

總結

沒有足夠的證據可判斷成年慢性氣喘病人應常規使用如Atrovent等抗膽鹼藥物。抗膽鹼藥物如Atrovent因屬支氣管擴張劑可打開肺內氣道而有時被用來治療氣喘病人。本回顧顯示，雖然此一治療(抗膽鹼藥物)優於安慰劑，但效果卻太小。當此藥與較常用的支氣管擴張劑(2促效劑如fenoterol)合併使用時並未呈現附加效益。然而，對於這些被分析的研究其品質令人關切。可以說某些成年慢性氣喘病人會對抗膽鹼藥物有所反應，但本回顧並未能鑑別他們的共同特質。