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 chr onic obstructive pulmonary disease (COPD) is modest; it has, however, been suggested that these patients may benefit from long term treatmen t. Methods - To investigate the efficacy of salmeterol in smokers with moderate to severe COPD a double blind, randomised, crossover compari son was performed between salmeterol (50 mu g twice daily) and placebo in 63 patients with stable COPD (mean age 65 years). Prior to inclusi on, 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 4 00 mu g inhaled salbutamol. Patients received four weeks of therapy wi th each of the treatment regimens. Assessment of efficacy was made wit h recording of morning and evening peak expiratory flow rates (PEF), r espiratory symptoms, and use of rescue salbutamol. FEV(1) was measured before and after nebulised salbutamol prior to randomisation and at t he end of each treatment period. Results - Morning PEF values were hig her 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 place bo than during the salmeterol period. The mean spirometric values (inc luding reversibility in FEV(1)) obtained at the end of the two treatme nt periods were similar. Compared with placebo, treatment with salmete rol was Denmark associated with lower daytime and night time symptom s cores and less use of rescue salbutamol both during the day and the ni ght. The patients rated the treatment with salmeterol better than trea tment with placebo. Conclusions - This study shows that, compared with placebo, treatment with salmeterol produces an improvement in respira tory symptoms and morning PEF values in patients with moderate to seve re COPD. Treatment with long acting beta agonists may therefore result in an improvement in functional status, even in patients suffering fr om apparently nonreversible obstructive pulmonary disease.