title: Effects of single or combined histamine H1-receptor and leukotriene CysLT1-receptor antagonism on nasal adenosine monophosphate challenge in persistent allergic rhinitis.
abstract: BACKGROUND
  The effects of single or combined histamine H(1)-receptor and leukotriene CysLT(1)-receptor antagonism on nasal adenosine monophosphate (AMP) challenge in allergic rhinitis are unknown.
  
  
  OBJECTIVE
  We elected to study the effects of usual clinically recommended doses of fexofenadine (FEX), montelukast (ML) and FEX + ML combination, compared with placebo (PL), on nasal AMP challenge in patients with persistent allergic rhinitis.
  
  
  METHODS
  Twelve patients with persistent allergic rhinitis (all skin prick positive to house dust mite) were randomized in a double-blind cross-over fashion to receive for 1 week either FEX 180 mg, ML 10 mg, FEX 180 mg + ML 10 mg combination, or PL, with nasal AMP challenge performed 12 h after dosing. There was a 1-week washout period between each randomized treatment. The primary outcome measure was the maximum percentage peak nasal inspiratory flow (PNIF) fall from baseline over a 60-min period after nasal challenge with a single 400 mg ml(-1) dose of AMP. The area under the 60-min time-response curve (AUC) and nasal symptoms were measured as secondary outcomes.
  
  
  RESULTS
  There was significant attenuation (P < 0.05) of the mean maximum percentage PNIF fall from baseline after nasal AMP challenge vs. PL, 48; with FEX, 37; 95% confidence interval for difference 2, 20; ML, 35 (4, 22); and FEX + ML, 32 (7, 24). The AUC (%.min) was also significantly attenuated (P < 0.05) vs. PL, 1893; with FEX, 1306 (30, 1143); ML, 1246 (214, 1078); and FEX + ML, 1153 (251, 1227). There were no significant differences for FEX vs. ML vs. FEX + ML comparing either the maximum or AUC response. The total nasal symptom score (out of 12) was also significantly improved (P < 0.05) vs. PL, 3.3; with FEX, 2.1 (0.3, 2.0); ML, 2.0 (0.5, 1.9); and FEX + ML, 2.5 (0.1, 1.4).
  
  
  CONCLUSIONS
  FEX and ML as monotherapy significantly attenuated the response to nasal AMP challenge and improved nasal symptoms compared with PL, while combination therapy conferred no additional benefit.
authors.affiliation: Asthma & Allergy Research Group, Department of Clinical Pharmacology, Ninewells Hospital & Medical School, University of Dundee, Scotland, UK.
authors.forename: Daniel K C
authors.initials: DK
authors.lastname: Lee
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Jackson
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Soutar
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Fardon
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lipworth
mesh_terms: D000085:Acetates / Q000627:therapeutic use*; D000328:Adult; D018592:Cross-Over Studies; D003521:Cyclopropanes; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D008297:Male; D009708:Nucleotidases; D011804:Quinolines / Q000627:therapeutic use*; D011969:Receptors, Histamine H1 / Q000627:therapeutic use*; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy*; D013440:Sulfides; D016593:Terfenadine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000085:Acetates; D003521:Cyclopropanes; D004338:Drug Combinations; D020024:Leukotriene Antagonists; D011804:Quinolines; D011969:Receptors, Histamine H1; D013440:Sulfides; D016593:Terfenadine; C093230:fexofenadine; D009708:Nucleotidases; C018775:adenosine monophosphatase; C093875:montelukast