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

• Published in: Journal of allergy and clinical immunology 1998-03, Vol.101 (3), p.312-319
• Main Authors: Aaronson, Donald, Kaiser, Harold, Dockhorn, Robert, Findlay, Steven, Korenblat, Philip, Thorsson, Lars, Källén, Anders
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Adolescent; Adrenocorticotropic Hormone - pharmacology; Adult; Allergic diseases; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - adverse effects; Anti-Inflammatory Agents - therapeutic use; Asthma; Asthma - drug therapy; Biological and medical sciences; budesonide; Budesonide - administration & dosage; Budesonide - adverse effects; Budesonide - therapeutic use; corticosteroids; Cosyntropin - pharmacology; Double-Blind Method; Female; HPA axis; Humans; Hydrocortisone - blood; Hypothalamo-Hypophyseal System - drug effects; Immunopathology; Male; Medical sciences; Middle Aged; Nebulizers and Vaporizers; Pituitary-Adrenal System - drug effects; Prednisone - administration & dosage; Prednisone - therapeutic use; Respiratory and ent allergic diseases; Turbuhaler
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/S0091-6749(98)70241-6

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 μg/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 μg/day, respectively); and by 35% in the prednisone group. The decrease was significant only in the 3200 μg/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 was the decrease significant ( p  = 0.03 vs placebo). Conclusions: In this study budesonide inhaled by means of the Turbuhaler, at doses recommended for clinical use (800 or 1600 μg/day), did not produce any statistically significant suppression of the HPA axis compared with placebo. (J Allergy Clin Immunol 1998;101:312-9.)