Methyl-xanthines for exacerbations of chronic obstructive pulmonary disease

International guidelines currently recommend the use of methyl-xanthines for exacerbations of chronic obstructive pulmonary disease (COPD) for patients who have incomplete responses to bronchodilators. However, available clinical trials are small and underpowered to evaluate the benefits and risks of methyl-xanthines in this acute setting.

To determine the benefit of methyl-xanthines compared to standard care for COPD exacerbations.

Randomised controlled trials (RCTs) were identified from the Cochrane Airways Review Group COPD Register which is a compilation of systematic searches of CINAHL, EMBASE, MEDLINE and CENTRAL and hand searching of 20 respiratory journals. In addition, primary authors and content experts were contacted to identify eligible studies. Bibliographies from included studies, known reviews and texts were also searched.

Only RCTs were eligible for inclusion. Studies were included if patients presented with acute COPD exacerbations and were treated with either methyl-xanthines (oral or intravenous) or placebo (with or without standard care) early in the acute treatment. Studies also needed to report either pulmonary function or admission results. Two reviewers independently selected potentially relevant articles and selected articles for inclusion. Methodological quality was independently assessed by two reviewers.

Data were extracted independently by two reviewers if the authors were unable to verify the validity of information. Missing data were obtained from authors or calculated from other data presented in the paper. The data were analysed using the Cochrane Review Manager 4.0.4 Studies were pooled to yield weighted mean differences (WMD) or odds ratios (OR) and reported using 95% confidence intervals (95%CI).

From 28 identified references, 4 RCTs met inclusion criteria (172 patients). Mean change in forced expiratory volume in one second (FEV1) at 2 hours was similar in methyl-xanthine and placebo groups (FEV1 WMD: -8 ml; 95% CI: -85 to 69 ml). The only study to report hospitalization rates showed a non-significant reduction with methyl-xanthines (OR: 0.3; 95% CI: 0.1 to 1.8) among 39 patients. Patients receiving methyl-xanthines had similar improvements in symptom scores, but reported more gastrointestinal side effects (OR: 5.3; 95% CI: 1.3 to 21.0) than patients receiving placebo.

There is no evidence to support the routine use of methyl-xanthines for COPD exacerbations. Methyl-xanthines do not appreciably improve FEV1 during COPD exacerbations and cause adverse effects; evidence of their effect on admissions is limited.