ASTHMA CONTROL DURING LONG-TERM TREATMENT WITH REGULAR INHALED SALBUTAMOL AND SALMETEROL

Background-The adverse effects of long term treatment of asthma with t he short acting beta agonist fenoterol have been established in both e pidemiological and clinical studies. A study was undertaken to investi gate the efficacy and safety of long term treatment with salbutamol an d salmeterol in patients with mild to moderate bronchial asthma. Metho ds-In a two centre double dummy crossover study 165 patients were rand omly assigned to receive salbutamol 400 mu g qid, salmeterol 50 mu g b id, or placebo via a Diskhaler. All patients used salbutamol as requir ed for symptom relief. The study comprised a four week run in and thre e treatment periods of 24 weeks, each of which was followed by a four week washout. Asthma control was assessed by measuring mean morning an d evening peak expiratory flow rate (PEFR), a composite daily asthma s core, and minor and major exacerbation rates. Washout assessments incl uded methacholine challenge and bronchodilator dose response tests. An alysis was by intention to treat. Results-Data from 157 patients were analysed. Relative to placebo, the mean morning PEFR increased by 30 l /min (95% CI 26 to 35) for salmeterol but did not change for salbutamo l. Evening PEFR increased by 25 l/min (95% CI 21 to 30) and 21 l/min ( 95% CI 17 to 26), respectively (p<0.001). Salmeterol improved the asth ma score compared to placebo (p<0.001), but there was no overall diffe rence with salbutamol. Only daytime symptoms were improved with salbut amol. The minor exacerbation rates were 0.29, 0.88, and 0.97 exacerbat ions/patient/year for salmeterol, salbutamol and placebo, respectively (p<0.0001 for salmeterol). The corresponding major exacerbation rates were 0.22, 0.51 and 0.40, respectively (p<0.03 for salmeterol). For s albutamol the asthma score deteriorated over time (p<0.01), and the ti me spent in major exacerbation was significantly longer compared with placebo (12.3 days (95% CI 4.2 to 20.4)) versus 8.4 days (95% CI 5.2 t o 11.6), p = 0.02). There was no evidence of rebound deterioration in asthma control, lung function, or bronchial hyperresponsiveness follow ing cessation of either active treatment, and no evidence of tolerance to salbutamol or salmeterol. Conclusions-Regular treatment with salme terol is effective in controlling asthma symptoms and reduces minor mo re than major exacerbation rates. Salbutamol was associated with impro ved daytime symptoms but subtle deterioration in asthma control occurr ed over time. Salbutamol should therefore be used only as required.