title: Suppression of hypothalamic-pituitary-adrenal axis activity with inhaled flunisolide and fluticasone propionate in adult asthma patients.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Medicine. Creighton University, Omaha, Nebraska 68131, USA. tbcasale@creighton.edu
authors.forename: T B
authors.initials: TB
authors.lastname: Casale
authors.forename: H S
authors.initials: HS
authors.lastname: Nelson
authors.forename: W E
authors.initials: WE
authors.lastname: Stricker
authors.forename: H
authors.initials: H
authors.lastname: Raff
authors.forename: K B
authors.initials: KB
authors.lastname: Newman
mesh_terms: D000280:Administration, Inhalation; D000311:Adrenal Glands / Q000187:drug effects*; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage / Q000009:adverse effects*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects*; D019540:Area Under Curve; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005446:Fluocinolone Acetonide / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives*; D000068298:Fluticasone; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects; D007700:Kinetics; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects
chemical_list: D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D005446:Fluocinolone Acetonide; C007734:flunisolide; D000068298:Fluticasone; D006854:Hydrocortisone