Additive effects of salmeterol and fluticasone or theophylline in COPD.

Background: β 2 -Agonists andcorticosteroids or theophylline can interact to produce beneficialeffects on airway function in asthma, but this has not been establishedin COPD. Methods: Eighty patients with well-controlledCOPD were randomized to receive 3 months of treatment in one of fourtreatment groups: (1) salmeterol, 50 μg bid; (2) salmeterol, 50 μg, plus fluticasone propionate, 250 μg bid; (3) salmeterol, 50 μg, plus fluticasone propionate, 500 μg bid; and (4) salmeterol, 50 μg, plus titrated theophylline bid. At each visit, a dose-response curve toinhaled salbutamol was constructed using a total cumulative dose of 800μg. Results: A gradual increase in FEV 1 was observed with each of the four treatments. Maximum significantincreases in FEV 1 over baseline values that were observedafter 3 months of treatment were as follows: salmeterol, 50 μg bid,0.163 L (95% confidence interval [CI], 0.080 to 0.245 L);salmeterol, 50 μg, plus fluticasone propionate, 250 μg bid, 0.188 L(95% CI, 0.089 to 0.287 L); salmeterol, 50 μg, plus fluticasonepropionate, 500 μg bid, 0.239 L (95% CI, 0.183 to 0.296 L); andsalmeterol, 50 μg, plus titrated theophylline bid, 0.157 L (95% CI,0.027 to 0.288 L). Salbutamol always caused a significantdose-dependent increase in FEV 1 (p 1 after salmeterol, 50 μg, plusfluticasone propionate, 500 μg bid, and that after salmeterol, 50μg, plus titrated theophylline bid or salmeterol, 50 μg bid, werestatistically significant(p Conclusion: These data show thatboth long-acting β 2 -agonists and inhaled corticosteroidshave a role in COPD. The data also show that fluticasone propionate andsalmeterol given together are more effective than salmeterol alone. Moreover, it suggests that the addition of fluticasone propionate tosalmeterol allows a greater improvement in lung function aftersalbutamol, although regular salmeterol is able to improve lungfunction in COPD patients without development of a true subsensitivityto its bronchodilator effect. In any case, patients must be treated forat least 3 months before a real improvement in lung function isachieved.