Review: methylxanthines are not effective for acute exacerbations of chronic obstructive pulmonary disease.

and commentary also appear in ACP Journal Club. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . For correspondence: Dr R G Barr, Columbia-Presbyterian Medical Center, New York, NY, USA. [email protected] Sources of funding: National Institutes of Health; Robert Wood Johnson Generalist Physician Faculty Scholar Award; Canadian Institute of Health Research. Methylxanthines (Meth) v placebo for acute exacerbations of chronic obstructive pulmonary disease* Outcomes Weighted event rates RRI (95% CI) NNH (CI) Meth v placebo Relapse within 7 days 13% v 11% 43% (247 to 287) Not significant Nausea or vomiting 37% v 14% 163% (35 to 415) 6 (4 to 14) Palpitations or arrhythmias 18% v 5% 262% (215 to 1446) Not significant Tremor 42% v 33% 31% (213 to 97) Not significant *Abbreviations defined in glossary; weighted event rates provided by author. RRI, NNH, and CI calculated from data in article using a fixed effects model. Follow up period for outcomes varied by trial. Commentary I t was not so long ago that most experts recommended theophylline as a first line agent for treating both stable and exacerbated COPD. Theophylline use increased dramatically during the 1970s, but then waned just as quickly during the 1990s. These rapid shifts in prescribing patterns were not strongly evidence based because large multicentre trials to evaluate clinical outcomes were never done. Despite the widespread use of theophylline in the past, Barr et al could identify only 4 trials of reasonable quality that assessed it as a treatment for COPD exacerbations. These 4 trials enrolled a total of only 169 patients. The lack of a standard protocol made it difficult to pool estimates for most outcomes. Overall, scant evidence exists that theophylline had any beneficial effect, but because of the small numbers of patients studied, clinically meaningful improvements might have been missed. Even if it confers some benefit, theophylline is probably a poor choice for treating acute COPD exacerbations because of the frequency of nausea and vomiting. Does this mean that we have heard the last of theophylline? Not necessarily. New findings suggest that theophylline may possess antiinflammatory effects at levels below those clinically used in the past. Moreover, secondary results from 2 large trials of stable COPD show that theophylline may prevent severe COPD exacerbations when given long term. 3 If these findings can be confirmed, theophylline might yet play an important role in the treatment of COPD, if not for treating exacerbations, then for their prevention. The low cost of generic theophylline might make it attractive for the treatment of stable COPD. Dennis E Niewoehner, MD Veterans Affairs Medical Center Minneapolis, Minnesota, USA 1 Barnes PJ. Theophylline: new perspectives for an old drug. Am J Respir Crit Care Med 2003;167:813–8. 2 Rossi A, Kristufek P, Levine BE, et al. Comparison of the efficacy, tolerability, and safety of formoterol dry powder and oral, slow-release theophylline in the treatment of COPD. Chest 2002;121:1058–69. 3 ZuWallack RL, Mahler DA, Reilly D, et al. Salmeterol plus theophylline combination therapy in the treatment of COPD. Chest 2001;119:1661–70. 80 THERAPEUTICS www.evidence-basedmedicine.com group.bmj.com on October 26, 2017 Published by http://ebm.bmj.com/ Downloaded from