Effect of theophylline associated with short-acting or long-acting inhaled beta2-agonists in patients with stable chronic obstructive pulmonary disease: a systematic review.

OBJECTIVES To determine whether, in stable patients with chronic obstructive pulmonary disease, administration of theophylline in combination with short-acting or long-acting inhaled beta2-agonists is more efficacious than is a placebo or each of these drugs used in isolation. METHODS A systematic review and meta-analysis were carried out. All randomized and double-blind clinical trials found in the literature were selected. RESULTS A total of eight studies were included. In comparing the effect of theophylline combined with beta2-agonists to that of a placebo, we found a statistically significant improvement in mean FEV1 (0.27 L; 95% CI: 0.11 to 0.43) and mean dyspnea (-0.78; 95% CI: -1.26 to -0.29). None of the meta-analyses performed detected any difference between the results obtained using theophylline combined with beta2-agonists and those obtained using beta2-agonists alone. When the administration of theophylline combined with beta2-agonists was compared to that of theophylline alone, there was a statistically significant improvement in mean dyspnea (-0.19; 95% CI: -0.34 to 0.04). CONCLUSION In patients with stable chronic obstructive pulmonary disease, theophylline combined with beta2 agonists is more efficacious than is a placebo in terms of improving FEV1 and dyspnea. In addition, theophylline combined with beta2 agonists is more efficacious than is theophylline in improving dyspnea. Furthermore, administration of theophylline combined with beta2 agonists is no more efficacious, for any of the variables studied, than is the use of beta2-agonists in isolation.