Dosage and Time Effects of Inhaled Budesonide on Bronchial Hyperreactivity

Abstract

In a double-blind study of 2 parallel groups of 15 allergic asthmatic patients each, we investigated whether treatment with inhaled budesonide has a dose- and time-dependent effect on the degree of bronchial hyperreactivity. The patients were randomly allocated to treatment with either 200 or 800 .mu.g budesonide per day for a period of 8 wk. The active treatment period was preceded by a selection period of 3 wk, and a single-blind placebo period of 2 wk. During these initial 5 wk the maintenance treatment of the patients, including cromolyn sodium and inhaled corticosteroids, was withheld. Spirometry and inhalation provocation tests with methacholine were carried out, and the symptom score was recorded every 2 wk. The methacholine provocation concentrations (geometric mean) causing a decrease in FEV1 of 20% (PC20) in the 200 and 800 .mu.g/day treatment groups just before the active treatment period were 0.90 and 0.91 mg/ml, respectively. These values increased significantly to 1.21 and 1.84 mg/ml after 2 wk of treatment (p < 0.05 and p < 0.001, respectively) and to 1.55 and 2.74 mg/ml after 8 wk of treatment (p < 0.01 and p < 0.001). During the whole study period budesonide in a dosage of 800 .mu.g/day induced a significantly larger change in PC20 than in a dosage of 200 .mu.g/day. The FEV1 before treatment was 91 .+-. 3% (SEM) and 84 .+-. 2% of the predicted value in the 200 and 800 .mu.g/day treatment groups, respectively. The FEV1 values after 2 wk treatment were 96 .+-. 3% and 93 .+-. 2%, respectively (p < 0.05 and p < 0.001). There was no further improvement in FEV1 during the following 6 wk of treatment, in contrast to the PC20 values. We conclude that inhaled budesonide can diminish bronchial hyeprreactivity in allergic asthmatic patients significantly and that this change is dose-dependent. Furthermore, the results indicate that the improvement in bronchial hyperreactivity is positively influenced by the duration of treatment.