Meta-analysis of efficacy and safety of oral theophylline in chronic obstructive pulmonary disease

Abstract

To evaluate the efficacy and safety of oral theophylline versus placebo in patients with stable chronic obstructive pulmonary disease (COPD). The databases Medline, Embase, Web of Science, Cochrane Central Register of Controlled Trials and Chinese Biomedical Database were retrieved by using the key words "Uniphyl or Theophylline or Theo-Dur or theo or Theotrim or Elixophyllin or Elixophyllin or Phyllocontin or aminophylline or Methylxanthine or nuelin or doxofylline" and "obstructive or bronchitis or pulmonary emphysema or bronchial hyperreactivity or COPD or COLD or emphysema" so as to search the materials about the randomized controlled clinical trials comparing the effectiveness of stable COPD treated by oral theophylline and placebo. A meta-analysis was conducted. For continuous variables, the results of individual studies were pooled using fixed-effect weighted mean difference (WMD) with a corresponding 95% confidence interval (CI). Where the results were expressed as dichotomous variables, the relative risk (RR) with 95%CI was calculated. Thirty-four documents about randomized controlled clinical trials, including a total of 2087 patients, from the retrieved 2010 documents accorded to the demand of enrollment. The results of meta-analysis showed that theophylline significantly improved the forced expiratory volume in 1 s, forced vital capacity and peak expiratory flow rate (WMD 0.09 L, 95%CI 0.09 - 0.09; WMD 0.14 L, 95%CI 0.13 - 0.14; WMD 17.0 L/min and 95%CI 6.9 - 27.2 respectively). Arterial oxygen tension and arterial carbon dioxide tension at rest both improved with treatment (WMD 2.89 mm Hg, 95%CI 1.11 - 4.66; WMD -2.05 mm Hg and 95%CI -3.59 to -1.42 respectively). Six-minute walk distance significantly improved (WMD 38.89 meters, 95%CI 21.55 - 56.22) in treatment group. The RR of acute exacerbations was smaller between both groups (RR 0.74, 95%CI 0.59 - 0.93). The RR of total adverse events was similar (RR 1.05, 95%CI 0.95 - 1.16) while RR of drug-related adverse events was greater (RR 2.54, 95%CI 1.37 - 4.70). And there was significant statistical difference. Compared with the placebo, theophylline can improve lung function, arterial blood gas tensions and walking distance while the incidence of drug-related adverse events is higher.