Methylxanthines for exacerbations of chronic obstructive pulmonary disease

  • Review
  • Intervention




Most international guidelines currently recommend methylxanthines (e.g., theophylline, aminophylline) for severe exacerbations of chronic obstructive pulmonary disease (COPD), yet clinical trials underlying this recommendation have been small and underpowered.


To determine the benefit of methylxanthines compared to placebo for COPD exacerbations.

Search methods

Randomised controlled trials (RCTs) were identified from the Cochrane Airways Review Group COPD Register, a compilation of systematic searches of CINAHL, EMBASE, MEDLINE and CENTRAL and hand searching of 20 respiratory journals. Primary authors and content experts were contacted to identify eligible studies. Bibliographies from included studies and reviews were searched. Searches are current to March 2005.

Selection criteria

Included studies were limited to RCTs of patients presenting with acute COPD exacerbations, treated with methylxanthines (oral or intravenous) or placebo plus standard care. Two reviewers independently selected articles for inclusion and assessed methodological quality.

Data collection and analysis

Two reviewers independently extracted data. Missing data were obtained from authors or calculated from other data presented in the paper. The data were analysed using the Cochrane Review Manager 4.1. Studies were pooled to yield weighted mean differences (WMD), standardised mean difference (SMD) or odds ratios (OR) and reported using 95% confidence intervals (95%CI).

Main results

From 29 identified references, 4 RCTs met inclusion criteria (169 patients). Mean change in forced expiratory volume in one second (FEV1) at 2 hours was similar in methylxanthine and placebo groups but transiently increased with methylxanthines at 3 days (WMD: 101 ml; 95% CI: 26 to 177). Data on clinical outcomes were sparse. Trends toward improvements in hospitalisation and length-of-stay were offset by a trend toward more relapses at one week. Changes in symptom scores were not significant. Methylxanthines caused more nausea and vomiting than placebo (OR: 4.6; 95% CI: 1.7 to 12.6) and trended toward more frequent tremor, palpitations, and arrhythmias.

Authors' conclusions

Given current evidence, methylxanthines should not be used for COPD exacerbations. Possible beneficial effects in lung function and clinical endpoints were modest and inconsistent, whereas adverse effects were significantly increased. More selective agents, tested in larger randomised trials, are necessary if methylxanthines are to have any role in the treatment of COPD exacerbations.



使用 methylxanthine 類藥物治療慢性阻塞性肺病的發作

目前大部分國際指引建議使用methylxanthine 類藥物(如:theophylline、 aminophylline) 治療慢性阻塞性肺病(COPD) 的嚴重發作,然而支持此項建議的臨床試驗都太小且證據力不足。




Cochrane Airways Review Group COPDRegister是彙編CINAHL、EMBASE、MEDLINE 和 CENTRAL等系統性搜尋的一個資料庫。我們從中找出隨機對照試驗。並以人工搜尋二十種呼吸道期刊。我們聯絡第一作者和內文專家以找出適當的研究。另外搜尋納研究和回顧性文章(reviews)的參考書目。目前搜尋到2005年3月。




兩位審查員各自獨立擷取數據。遺失的數據則詢問作者,或從文章中的其他數據計算而來。以Cochrane Review Manager 4.1 Studies分析數據。匯集各個研究以產生加權平均差(weighted mean difference,WMD)、標準化平均差(standardised mean difference, SMD)或危險對比值(odds ratio,OR),並以95%信賴區間(95% CI)進行報告。


在找到的二十九篇參考資料中,有四個隨機對照試驗符合納入標準(共169位病患)。治療後兩小時,Methylxanthine組和安慰劑組的第1秒用力呼氣量(FEV1)的平均變化相似,但治療後第三天,methylxanthine 組則有暫時性的增加(加權平均差:101毫升;95%信賴區間:26到177)。有關臨床結果的數據不多。methylxanthine組似乎在住院和住院天數方面,有改善的趨勢;但治療後第一週的發作次數卻多於安慰劑組。症狀分數的改變不明顯。與安慰劑相比,methylxanthine類藥物造成比較多的噁心和嘔吐(危險對比值:4.6;95%信賴區間:1.7到12.6),且較容易發生顫抖、心悸和心律不整等。




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



Plain language summary

Methylxanthines for exacerbations of chronic obstructive pulmonary disease

Methylxanthine drugs such as aminophylline and theophylline are recommended for use in patients who have acute exacerbations (episodes) of chronic obstructive pulmonary disease, particularly for patients unresponsive to standard therapies. This review identified four studies that compared these drugs with placebo. Over the first 2 hours of treatment there was no evidence that patients improved in terms of lung function, although a possible late benefit was detected. The studies do not give a clear indication of whether there was benefit in terms of reduced symptoms or hospital admissions, but side effects were found to be more common with methylxanthines. We conclude that, given current evidence, methylxanthines should not be used for acute exacerbations of chronic obstructive pulmonary disease.