title: Significant variability in response to inhaled corticosteroids for persistent asthma.
abstract: BACKGROUND
  A clinical model is needed to compare inhaled corticosteroids (ICSs) with respect to efficacy.
  
  
  OBJECTIVE
  The purpose of this investigation was to compare the relative beneficial and systemic effects in a dose-response relationship for 2 ICSs.
  
  
  METHODS
  A 24-week, parallel, open-label, multicenter trial examined the benefit-risk ratio of 2 ICSs in persistent asthma. Benefit was assessed by improvements in FEV(1) and PC(20); risk was assessed by overnight plasma cortisol suppression. Thirty subjects were randomized to either beclomethasone dipropionate (BDP) 168, 672, and 1344 microg/day (n = 15) or fluticasone propionate (FP) 88, 352, and 704 microg/day (n = 15), both administered by means of a metered dose inhaler (MDI) with chlorofluorocarbon propellant via a spacer, in 3 consecutive 6-week intervals; this was followed by 3 weeks of FP dry powder inhaler (DPI) 2000 microg/day.
  
  
  RESULTS
  Maximum FEV(1) response occurred with the low dose for FP-MDI and the medium dose for BDP-MDI and was not further increased by treatment with FP-DPI. Near-maximum methacholine PC(20) improvement occurred with the low dose for FP-MDI and the medium dose for BDP-MDI. Both BDP-MDI and FP-MDI caused dose-dependent cortisol suppression. Responsiveness to ICS treatment was found to vary markedly among subjects. Good (>15%) FEV(1) response, in contrast to poor (<5%) response, was found to be associated with high exhaled nitric oxide (median, 17.6 vs 11.1 ppb), high bronchodilator reversibility (25.2% vs 8.8%), and a low FEV(1)/forced vital capacity ratio (0.63 vs 0.73) before treatment. Excellent (>3 doubling dilutions) improvement in PC(20), in contrast to poor (<1 doubling dilution) improvement, was found to be associated with high sputum eosinophil levels (3.4% vs 0.1%) and older age at onset of asthma (age, 20-29 years vs <10 years).
  
  
  CONCLUSIONS
  Near-maximal FEV(1) and PC(20) effects occurred with low-medium dose for both ICSs in the subjects studied. High-dose ICS therapy did not significantly increase the efficacy measures that were evaluated, but it did increase the systemic effect measure, overnight cortisol secretion. Significant intersubject variability in response occurred with both ICSs. It is possible that higher doses of ICSs are necessary to manage more severe patients or to achieve goals of therapy not evaluated in this study, such as prevention of asthma exacerbations.
authors.affiliation: National Jewish Medical and Research Center, Department of Pediatrics, Denver, CO 80206, USA.
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Szefler
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Martin
authors.forename: Tonya Sharp
authors.initials: TS
authors.lastname: King
authors.forename: Homer A
authors.initials: HA
authors.lastname: Boushey
authors.forename: Reuben M
authors.initials: RM
authors.lastname: Cherniack
authors.forename: Vernon M
authors.initials: VM
authors.lastname: Chinchilli
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Craig
authors.forename: Myrna
authors.initials: M
authors.lastname: Dolovich
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Drazen
authors.forename: Joanne K
authors.initials: JK
authors.lastname: Fagan
authors.forename: John V
authors.initials: JV
authors.lastname: Fahy
authors.forename: James E
authors.initials: JE
authors.lastname: Fish
authors.forename: Jean G
authors.initials: JG
authors.lastname: Ford
authors.forename: Elliot
authors.initials: E
authors.lastname: Israel
authors.forename: James
authors.initials: J
authors.lastname: Kiley
authors.forename: Monica
authors.initials: M
authors.lastname: Kraft
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Lazarus
authors.forename: Robert F
authors.initials: RF
authors.lastname: Lemanske
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Mauger
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Peters
authors.forename: Christine A
authors.initials: CA
authors.lastname: Sorkness
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D001507:Beclomethasone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002908:Chronic Disease; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D016210:Methacholine Chloride; D000068298:Fluticasone; D001507:Beclomethasone; D006854:Hydrocortisone