Background: International guidelines indicate that the long-acting bronchodilators play a key role in the treatment of patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to assess the short term efficacy and safety of 50 and 100 microg bid inhaled salmeterol, compared with placebo and orally dose titrated slow-release theophylline in patients with stable COPD.
Methods: Thirteen patients (67+/-7 years, three females) with moderate-to-severe COPD (FEV1<70% predicted and >30% predicted) and with poor reversibility (post-bronchodilator FEV1<12% and <200 ml from pre-bronchodilator values) completed this single centre randomised, double-blind, double-dummy, four-phase cross-over clinical trial. Patients were randomised to treatment after a 2-week oral corticosteroid trial and a theophylline titration phase. Each treatment lasted 2 week with a 2-week washout period. Values at the end of treatments were compared.
Results: Inhaled salmeterol at both tested doses was better than placebo in improving lung function (FEV1, FVC, and morning PEF) of stable patients with moderate COPD over a period of 2 weeks. Although slight (about 170 ml, 150 ml, and 120 ml/min on average, for FEV1, FVC, and PEF, respectively) the improvement was significant. The effects seem to improve only slightly with the higher dose. Salmeterol appeared to be more effective than theophylline treatment when compared to placebo, as theophylline improved significantly, but less, the FEV1 (about 80 ml, on average) without affecting any of the other lung function variables. Salmeterol 100 microg was significantly better than theophylline in improving morning PEF. Four patients reported five adverse events while receiving placebo and 2 and 3 patients reported 2 and 3 adverse events, respectively, during salmeterol 50 microg and salmeterol 100 microg phases. None was considered drug related. Five patients experienced 13 adverse events with theophylline treatment, four of which were considered drug related.
Conclusion: Inhaled salmeterol improves lung function in stable patients with moderate-to-severe and poorly reversible COPD. The magnitude of improvement in FEV1 observed in this study is similar to that found in longer and larger studies on similar populations of patients. In those studies, that improvement was associated with a better quality of life and less symptoms. Theophylline determined a smaller improvement in FEV1 with more unpleasant side effects that both doses of inhaled salmeterol, though there was no significant difference. It is concluded that salmeterol is an effective and well tolerated therapy, potentially preferable to theophylline, at least in the short-term management of stable COPD.