BUDESONIDE TREATMENT OF MODERATE AND SEVERE ASTHMA IN CHILDREN - A DOSE-RESPONSE STUDY

Objective: The purpose of the study was to evaluate the dose-response relationships of the inhaled corticosteroid budesonide in a double blind crossover study in 19 children with moderate and severe asthma. Methods: A 2-week placebo treatment period (run-in) was followed by three 4-week treatment periods during which 100, 200, and 400 mu g of budesonide were given per day in randomized order. Urinary cortisol excretion, lung functions, and protection against exercise-induced asthma were assessed at the end of run-in and each treatment period. Furthermore, morning and evening peak expiratory pow rates, day and night symptoms, and use of rescue beta(2)-agonists were recorded throughout the study. Results: One hundred micrograms of budesonide per day markedly improved symptoms, morning and evening peak expiratory pow rates, and use of rescue beta(2)-agonists (p < 0.01). No further improvement was seen in these parameters with increasing doses of budesonide. In contrast, a significant dose-response effect was found on lung functions measured at the hospital and fall in lung functions after exercise (p < 0.001); 200 mu g was significantly better than 100 mu g, and 400 mu g was significantly better than 200 mu g. About 53% of the maximum effect against exercise-induced asthma was achieved by the lowest budesonide dose (p < 0.001), and about 83% by the highest dose. No significant differences were seen in urinary cortisol excretion between run-in and the various budesonide doses. Conclusions: Low doses of budesonide, which are not associated with any systemic side effects, have a marked antiasthma effect in children. Protection against exercise-induced asthma requires higher doses than achievement of symptom control.