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Suppression of hypothalamic-pituitary-adrenal axis activity with inhaled flunisolide and fluticasone propionate in adult asthma patients. Ann Allergy Asthma Immunol 2001 Nov;87(5):379-85

Date

12/04/2001

Pubmed ID

11730179

DOI

10.1016/S1081-1206(10)62918-3

Scopus ID

2-s2.0-0035165073 (requires institutional sign-in at Scopus site)   67 Citations

Abstract

BACKGROUND: Suppression of the hypothalamic-pituitary-adrenal (HPA) axis, a potential systemic effect of inhaled corticosteroid therapy, can be quantified by monitoring serum, urinary, and salivary cortisol levels.

OBJECTIVES: 1) Compare the effects on HPA axis of the inhaled corticosteroids flunisolide and fluticasone propionate versus placebo and oral prednisone. 2) Estimate dose-potency ratio for HPA-axis suppression.

METHODS: Multicenter, randomized, placebo-controlled, open-label, 21-day trial. Active regimens were flunisolide 500 and 1,000 microg, twice daily; fluticasone propionate 110, 220, 330, and 440 microg, twice daily; and prednisone, 7.5 mg daily. Enrolled patients were nonsmokers, 18 to 50 years of age, with persistent mild-to-moderate asthma and had not used oral, nasal, or inhaled corticosteroids for 6 months before study. Main outcome measures were area under serum cortisol concentration curve for 22 hours (AUC(0-22h)); 24-hour urinary cortisol level; and 8 AM salivary cortisol level.

RESULTS: One hundred fifty-three patients were randomly assigned to active treatment or placebo; 125 patients completed the study and were at least 80% compliant with their regimens. Both fluticasone propionate and flunisolide caused dose-dependent suppression of HPA axis, which was statistically greater for fluticasone propionate (P = 0.0003). Dose-potency ratio showed 4.4 times more serum-cortisol suppression/microgram increase in dose with fluticasone propionate than with flunisolide. Diurnal pattern of serum cortisol suppression was persistent with fluticasone propionate and "remitting" with flunisolide. Salivary and urinary cortisol data were qualitatively similar to serum cortisol results.

CONCLUSIONS: Fluticasone caused significantly more suppression of HPA axis than flunisolide. Flunisolide may provide a safe option for patients with asthma requiring long-term inhaled corticosteroid therapy.

Author List

Casale TB, Nelson HS, Stricker WE, Raff H, Newman KB

Author

Hershel Raff PhD Professor in the Academic Affairs department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Administration, Inhalation
Adrenal Glands
Adult
Androstadienes
Anti-Asthmatic Agents
Anti-Inflammatory Agents
Area Under Curve
Asthma
Dose-Response Relationship, Drug
Female
Fluocinolone Acetonide
Fluticasone
Humans
Hydrocortisone
Hypothalamus
Kinetics
Male
Pituitary Gland