Randomised trial of an inhaled β2 agonist, inhaled corticosteroid and their combination in the treatment of asthma

Background-Although many asthmatic patients are treated with a combination of beta(2), agonist and corticosteroid inhalers, the clinical effects of combining the drugs are unknown. Studies on the early asthmatic response to allergen suggest that beta(2) agonists may reduce the benefit of inhaled corticosteroids. A study of the effects of combining the drugs on asthma control was undertaken. Methods-Sixty one subjects with mild to moderate asthma were randomised to a double blind crossover comparison of inhaled budesonide (200-400 mu g twice daily), terbutaline (500-1000 pg four times daily), combined treatment, and placebo. Each treatment was given for six weeks following a four week washout period. Ipratropium was used for symptom relief. Treatments were ranked from worst (1) to best (4) based on need for oral steroid, mean morning peak flow, nocturnal awakening, ipratropium use, and asthma symptoms. Lung function and bronchial hyperresponsiveness were measured before and after each treatment. Results-Evaluable data for all four treatments were obtained from 47 subjects. The mean rank of each treatment was: placebo 2.05; terbutaline = 2.13; budesonide 2.48; combined treatment = 3.34. Combined treatment was ranked significantly better than any other treatment (p<0.01). Mean (95% CI) morning and evening peak flows were 14 (5 to 23) and 24 (15 to 34) 1/min higher, respectively, during combined treatment than during budesonide, and 27 (17 to 37) and 15 (7 to 23) 1/min higher than during terbutaline. Asthma symptoms tended to be least frequent during combined treatment but were not significantly different from budesonide alone. There was no significant difference between combined treatment and budesonide alone for lung function and bronchial hyperresponsiveness. Conclusions-In this group of mild to moderate asthmatic subjects the combination of beta(2), agonist and corticosteroid gave better asthma control than either treatment alone. There was no evidence that regular beta(2) agonist treatment impaired the beneficial effect of inhaled corticosteroid.