Suppression of hypothalamic-pituitary-adrenal axis activity with inhaled flunisolide and fluticasone propionate in adult asthma patients

Background: Suppression of the hypothalamic-pituitary-adrenal (HPA) axis, a potential systemic effect of inhaled corticosteroid therapy, can be quanti fied by monitoring serum, urinary, and salivary cortisol levels. Objectives: 1) Compare the effects on HPA axis of the inhaled corticosteroi ds flunisolide and fluticasone propionate versus placebo and oral prednison e. 2) Estimate dose-potency ratio for HPA-axis suppression. Methods: Multicenter, randomized, placebo-controlled, open-label, 21-day tr ial. Active regimens were flunisolide 500 and 1,000 lag, twice daily; fluti casone propionate 110, 220, 330, and 440 mug, twice daily; and prednisone, 7.5 mg daily. Enrolled patients were nonsmokers, 18 to 50 years of age, wit h persistent mild-to-moderate asthma and had not used oral, nasal, or inhal ed corticosteroids for 6 months before study. Main outcome measures were ar ea under serum cortisol concentration curve for 22 hours (AUC(0-22h)); 24-h our 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 flunisolid e caused dose-dependent suppression of HPA axis, which was statistically gr eater for fluticasone propionate (P = 0.0003). Dose-potency ratio showed 4. 4 times more serum-cortisol suppression/microgram increase in dose with flu ticasone propionate than with flunisolide. Diurnal pattern of serum cortiso l suppression was persistent with fluticasone propionate and "remitting" wi th flunisolide. Salivary and urinary cortisol data were qualitatively simil ar to serum cortisol results. Conclusions: Fluticasone caused significantly more suppression of HPA axis than flunisolide. Flunisolide may provide a safe option for patients with a sthma requiring long-term inhaled corticosteroid therapy.