EFFICACY OF INHALED SALMETEROL IN THE MANAGEMENT OF SMOKERS WITH CHRONIC OBSTRUCTIVE PULMONARY-DISEASE - A SINGLE-CENTER RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, CROSSOVER STUDY

Background- The acute response to bronchodilators in patients with chronic obstructive pulmonary disease (COPD) is modest; it has, however, been suggested that these patients may benefit from long term treatment. Methods - To investigate the efficacy of salmeterol in smokers with moderate to severe COPD a double blind, randomised, crossover comparison was performed between salmeterol (50 mu g twice daily) and placebo in 63 patients with stable COPD (mean age 65 years). Prior to inclusion, all patients had a forced expiratory volume in one second (FEV(1)) of <60% of predicted and an improvement in FEV(1) of <15% following 400 mu g inhaled salbutamol. Patients received four weeks of therapy with each of the treatment regimens. Assessment of efficacy was made with recording of morning and evening peak expiratory flow rates (PEF), respiratory symptoms, and use of rescue salbutamol. FEV(1) was measured before and after nebulised salbutamol prior to randomisation and at the end of each treatment period. Results - Morning PEF values were higher during the salmeterol than during the placebo period, although the mean treatment difference was small (12 1/min (95% confidence limits 6 to 17)). No difference in mean evening PEF values was found. Diurnal variation in PEF, assessed as the difference between the morning PEF and that of the previous evening, was more pronounced during the placebo than during the salmeterol period. The mean spirometric values (including reversibility in FEV(1)) obtained at the end of the two treatment periods were similar. Compared with placebo, treatment with salmeterol was Denmark associated with lower daytime and night time symptom scores and less use of rescue salbutamol both during the day and the night. The patients rated the treatment with salmeterol better than treatment with placebo. Conclusions - This study shows that, compared with placebo, treatment with salmeterol produces an improvement in respiratory symptoms and morning PEF values in patients with moderate to severe COPD. Treatment with long acting beta agonists may therefore result in an improvement in functional status, even in patients suffering from apparently nonreversible obstructive pulmonary disease.