Purpose of the Study
To evaluate the efficacy and safety of dry powder inhaled budesonide in the treatment of children with moderate to severe persistent asthma.
Four hundred four children (6 to 18 years old) with forced expiratory volume in 1 second (FEV1) between 50% and 80%, using at least two asthma medications and with a minimum 6-month history of inhaled glucocorticosteroid-dependent asthma were enrolled in a randomized, double-blind, placebo-controlled, parallel group, multicenter study.
The patients received either 100, 200, 400 μg of budesonide or placebo twice daily for 12 weeks. Pulmonary function tests were performed in the early morning of each clinic visit that where scheduled at 2 week intervals during the study. Peak expiratory flow (PEF) was measured by the patients in the morning. The patients recorded daytime and nighttime asthma symptom scores. Adverse effects were also recorded. Early morning basal cortisol levels and stimulated plasma cortisol levels were measured before randomization and at the end of the study period. The patients received physical examinations, electrocardiograms, and chest-radiographs at baseline and at the end of the study period.
Three hundred five of the 404 patients completed the double-blind period. The dropout rates were 49% for the placebo-treated group and 15% to 18% for the active treatment groups. Morning PEF decreased by 3.9% in the placebo-treated group, whereas there were mean increases of 4.4%, 5.6%, and 6.7% in the groups receiving 100, 200, 400 μg of budesonide twice daily, respectively (P < .001). FEV1 had a mean decrease of 4.6% in the placebo-treated group. There was a dose-dependent improvement (P = .015) in FEV1 with mean increases of 3.1%, 7.7%, and 7.3% in the groups treated with 100, 200, 400 μg of budesonide twice daily, respectively. Daytime and nighttime symptom scores improved (P = .001) in the active treatment groups. There was a 26% increase in inhaled bronchodilator use in the placebo-treated group and a decrease of 24%, 30%, and 40% in the groups receiving 100, 200, 400 μg of budesonide twice daily, respectively (P = .001). A dose-dependent relationship was also noted (P = .036). There was no significant change from baseline in cortisol levels. No significant adverse effects were noted between the four groups.
Dry powder inhaled budesonide provided a dose-dependent improvement in pulmonary function and clinical symptoms and was well-tolerated in children with moderate to severe persistent asthma.
The dry powder inhaler is an efficient and well-tolerated system for medication delivery that is less technique dependent than conventional metered dose inhalers. This study does not compare the efficacy of budesonide with other inhaled glucocorticosteroids or maintenance antiinflammatory medications. Also, no suppression of the hypothalamic-pituitary-adrenal axis was noted during the 12-week study period.