Effects of budesonide by means of the turbuhaler on the hypothalmic-pituitary-adrenal axis in asthmatic subjects:: A dose-response study

Background: As a general phenomenon, corticosteroids may suppress the activity in the hypothalamic-pituitary-adrenal (HPA) axis. The adrenal stimulation test is a commonly used method to assess the relative risk of exogenous corticosteroids to induce systemic side effects. Objectives: This clinical trial was performed to assess the effects of budesonide on the HPA axis (at 800, 1600, or 3200 mu g/day, given as a twice daily regimen, administered by means of the Turbuhaler) in adult patients with mild, non-steroid-dependent asthma. Methods: Sixty-four asthmatic patients received budesonide or placebo by inhalation or 10 mg/day oral prednisone once daily as a positive control in a double-blind, double-dummy, randomized, placebo-controlled, parallel-group, multicenter study. Plasma cortisol concentration was measured to assess the effect on the HPA axis before and during a 6-hour infusion of synthetic adrenocorticotropic hormone (ACTH), cosyntropin. Results: After 6 weeks of treatment, plasma cortisol concentrations after adrenal stimulation by cosyntropin infusion had fallen by 4% in the placebo group; by 13%, 11%, and 27% in the budesonide groups (800, 1600, and 3200 mu g/day respectively); and by 35% in the prednisone group. The decrease was significant only in the 3200 mu g/day budesonide (p = 0.03) and prednisone (p = 0.005) groups. Over the same time period, decreases in basal plasma cortisol concentrations were 1% in the placebo group; 19%, 19%, and 34% in the three budesonide groups; and 37% in the prednisone group. Only in the prednisone group nas the decrease significant (p = 0.03 vs placebo). Conclusions: In this study budesonide inhaled by means of the Turbuhaler, al doses recommended for clinical use (800 or 1600 mu g/day), did not produce any statistically significant suppression of the HPA axis compared with placebo.