title: Prolonged protection of the new inhaled corticosteroid fluticasone furoate against AMP hyperresponsiveness in patients with asthma.
abstract: BACKGROUND
  Single-dose inhaled corticosteroids (ICS) induce direct anti-inflammatory effects in asthma thereby improving airway hyperresponsiveness (AHR). A novel enhanced-affinity ICS, fluticasone furoate (FF), demonstrated a prolonged duration of action in vitro. The aim of this study was to evaluate the efficacy and duration of action of a single dose of FF by studying protection against AHR to adenosine 5'-monophosphate (AMP) and effects on exhaled nitric oxide (eNO).
  
  
  METHODS
  A randomized, double-blind, placebo-controlled, 6-way crossover study (FFA10026) was performed in 24 patients with allergic asthma (mean age 32.8 years, FEV(1) ≥ 70% predicted and PC(20) AMP ≤ 50 mg/ml). Each subject received a single dose of FF 1000 μg, fluticasone proprionate (FP) 1000 μg, or placebo at 2 (FF only), 14 or 26 h prior to AMP challenge and eNO measurement.
  
  
  RESULTS
  FF significantly improved PC(20) AMP compared to placebo, the difference in doubling concentrations being 2.18 (95% confidence interval: 1.13-3.23), 1.54 (0.48-2.59), and 1.30 (0.26-2.34) at 2, 14 and 26 h. FP improved PC(20) AMP significantly at 14 h compared to placebo, but not at the 26-hour time point, the difference in doubling concentrations being 1.72 (0.70-2.75) and 0.33 (-0.69-1.34). There was no significant effect on eNO after either FF or FP at all time points. FF was well tolerated and there were no serious adverse events.
  
  
  CONCLUSIONS
  The new inhaled corticosteroid FF, but not FP, demonstrates prolonged protection up to 26 h against AHR to AMP in asthma patients.
authors.affiliation: Department of Pulmonary Diseases, University Medical Center Groningen, The Netherlands. m.van.den.berge@int.umcg.nl
authors.forename: M
authors.initials: M
authors.lastname: van den Berge
authors.forename: B
authors.initials: B
authors.lastname: Luijk
authors.forename: P
authors.initials: P
authors.lastname: Bareille
authors.forename: N
authors.initials: N
authors.lastname: Dallow
authors.forename: D S
authors.initials: DS
authors.lastname: Postma
authors.forename: J-W J
authors.initials: JW
authors.lastname: Lammers
mesh_terms: D000249:Adenosine Monophosphate / Q000009:adverse effects; D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage* / Q000009:adverse effects; D018926:Anti-Allergic Agents / Q000008:administration & dosage; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage; D018592:Cross-Over Studies; D004311:Double-Blind Method; D045853:Exhalation; D005260:Female; D000068298:Fluticasone; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy*; D008297:Male; D009569:Nitric Oxide / Q000032:analysis; D012129:Respiratory Function Tests
chemical_list: D000305:Adrenal Cortex Hormones; D000730:Androstadienes; D018926:Anti-Allergic Agents; D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D009569:Nitric Oxide; D000249:Adenosine Monophosphate; D000068298:Fluticasone; C523187:fluticasone furoate