title: Effects of low-dose fluticasone propionate/salmeterol combination therapy on exhaled nitric oxide and nitrite/nitrate in breath condensates from patients with mild persistent asthma.
abstract: OBJECTIVE
  The long-acting β2-agonist salmeterol in combination with the corticosteroid fluticasone propionate is used in clinical practice for the treatment of mild persistent asthma. Although the effect of fluticasone propionate alone in asthmatic patients is well documented, the effect of fluticasone propionate/salmeterol (FSC) combination therapy on airway inflammation and airway hyperresponsiveness (AHR) is not well characterized. Thus, we evaluated AHR, exhaled nitric oxide (FE(NO)), and nitrite and nitrate in exhaled breath condensates (EBCs) from mild persistent asthmatic patients treated with a low-dose FSC (100/50).
  
  
  METHODS
  In this open label study, 18 mild persistent, steroid-naïve asthmatics (age, 22-62 years, forced expiratory volume in 1 s (FEV(1)) > 70% predicted, provocative dose resulting in 20% reduction (PD(20)) < 10 mg/mL) were treated with FSC 100/50 for 4 weeks. PD(20) to methacholine, FEV(1), FE(NO), and EBC nitrite and nitrate was measured before and after treatment.
  
  
  RESULTS
  After 4 weeks of therapy with FSC 100/50, FE(NO) decreased from 74 ppb (SD = 37) to 34 ppb (SD = 15) (p < .001). FEV(1) (% predicted) increased from 89.4 (SD = 10.7) to 93.3 (SD = 9.5) (p < .01). The PD(20) for methacholine increased from 3.0 (±3.2) to 10.3 (±8.4) mg/mL (p < .01) in 3 of 18 patients reaching the maximum allowable dose (25 mg/mL). FE(NO) correlated with the log of the methacholine dose. There was no statistically significant change in EBC nitrite and nitrate before and after treatment.
  
  
  CONCLUSIONS
  Treatment of mild persistent, steroid-naïve asthmatics with low-dose combination therapy is effective in rapidly reducing airway inflammation and AHR. Our results suggest different metabolic origins for nitrite, nitrate, and FE(NO) in this group of patients.
authors.affiliation: Division of Allergy and Immunology, Albany Medical College, Albany, NY, USA.
authors.forename: M Asghar
authors.initials: MA
authors.lastname: Pasha
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Smith
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Feustel
authors.forename: David
authors.initials: D
authors.lastname: Jourd'heuil
mesh_terms: D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000730:Androstadienes / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism*; D001944:Breath Tests; D001985:Bronchial Provocation Tests; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D003430:Cross-Sectional Studies; D004338:Drug Combinations; D000068297:Fluticasone-Salmeterol Drug Combination; D006801:Humans; D016014:Linear Models; D008875:Middle Aged; D009566:Nitrates / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000730:Androstadienes; D001993:Bronchodilator Agents; D004338:Drug Combinations; D000068297:Fluticasone-Salmeterol Drug Combination; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D000420:Albuterol