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Methylxanthines for exacerbations of chronic obstructive pulmonary disease: meta-analysis of randomised trials

BMJ 2003; 327 doi: (Published 18 September 2003) Cite this as: BMJ 2003;327:643
  1. R Graham Barr, assistant professor of medicine and epidemiology (rgb9{at},
  2. Brian H Rowe, professor2,
  3. Carlos A Camargo, Jr, assistant professor of medicine and epidemiology3
  1. 1Division of General Medicine, PH-9 East Room 105, Columbia-Presbyterian Medical Centre, 622 West 168th Street, New York, NY 10032, USA
  2. 2Division of Emergency Medicine, University of Alberta, Edmonton, AB, Canada T6G 2B7
  3. 3Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA021143, USA
  1. Correspondence to: R Graham Barr
  • Accepted 11 July 2003


Objective To evaluate the addition of methylxanthines to standard treatments in patients presenting with acute exacerbations of chronic obstructive pulmonary disease (COPD).

Design Meta-analysis of randomised controlled trials.

Data source The Cochrane airways review group's COPD register. Two reviewers independently selected articles for inclusion, assessed methodological quality, and extracted data.

Selection of studies Four trials met the inclusion criteria, with 169 patients.

Main outcome measures Mean change in spirometry, clinical end points, symptom scores, and adverse events.

Results Mean change in forced expiratory volume at one second at two hours was similar in methylxanthine and placebo groups but transiently increased with methylxanthines at three days. Non-significant reductions in admissions to hospital and length of stay were offset by a non-significant increase in relapses at one week. Changes in symptom scores did not reach significance. Methylxanthines caused more nausea and vomiting than placebo (odds ratio 4.6, 95% confidence interval 1.7 to 12.6), and non-significant increases in tremor, palpitations, and arrhythmias were also observed.

Conclusions The available data do not support the use of methylxanthines for the treatment of exacerbations of chronic obstructive pulmonary disease. Potential benefits of methylxanthines for lung function and symptoms were generally not confirmed at standard levels of significance, whereas the potentially important adverse events of nausea and vomiting were significantly increased in patients receiving methylxanthines.


  • Funding Supported by grants PE-11001, HL-07427, and HL-63841 from the National Institutes of Health. RGB is funded by a Robert Wood Johnson Generalist Physician Faculty Scholar Award and BHR by the Canadian Institute of Health Research.

  • Competing interests None declared.

  • Accepted 11 July 2003
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