title: Effects of mediator antagonism on mannitol and adenosine monophosphate challenges.
abstract: BACKGROUND
  Airway hyper-responsiveness (AHR) to indirect stimuli is a useful non-invasive surrogate inflammatory marker in the evaluation of asthma, while histamine and cysteinyl leukotrienes are important inflammatory mediators.
  
  
  OBJECTIVE
  To evaluate AHR to indirect bronchoconstrictor stimuli and time taken to recover following single doses of montelukast 10 mg and desloratadine 5 mg in combination, montelukast 10 mg alone and placebo.
  
  
  METHODS
  Fifteen mild-to-moderate persistent asthmatics completed a randomized, double-blind, cross-over study. Patients received encapsulated montelukast 10 mg/desloratadine 5 mg combination, montelukast 10 mg alone and placebo, 10-14 h prior to challenge on two separate occasions. The mannitol threshold dose, AMP threshold concentration and recovery times after challenge were measured along with lung function.
  
  
  RESULTS
  Compared to placebo, montelukast/desloratadine conferred improvements (P < 0.05) in adenosine monophosphate (AMP) threshold concentration and mannitol threshold dose: a 3.2-fold (95% CI 2.2-4.6) and 2.4-fold (95% CI 1.7-3.3) difference, respectively, while compared to montelukast this amounted to a 2.0-fold (95% CI 1.2-3.4) and 1.5-fold (95% CI 1.1-2.4) improvement, respectively. Montelukast was not significantly different from placebo. Both montelukast/desloratadine and montelukast compared to placebo, shortened recovery following both challenges (P < 0.05): a 27-min (95% CI 17-37) and 29-min (95% CI 20-36) reduction, respectively, for AMP, and a 27-min (95% CI 17-37) and 26-min (95% CI 17-35) reduction, respectively for mannitol.
  
  
  CONCLUSIONS
  The dissociated effects of single doses of montelukast alone but not montelukast/desloratadine combination on AHR and recovery time, highlights the relative roles of histamine in initiating the bronchoconstrictor response and cysteinyl leukotrienes in sustaining it. Similar improvements in AHR and recovery time were observed following both indirect bronchoconstrictor stimuli.
authors.affiliation: Asthma & Allergy Research Group, Ninewells Hospital & Medical School, University of Dundee, Dundee, UK.
authors.forename: G P
authors.initials: GP
authors.lastname: Currie
authors.forename: K
authors.initials: K
authors.lastname: Haggart
authors.forename: D K C
authors.initials: DK
authors.lastname: Lee
authors.forename: S J
authors.initials: SJ
authors.lastname: Fowler
authors.forename: A M
authors.initials: AM
authors.lastname: Wilson
authors.forename: J D
authors.initials: JD
authors.lastname: Brannan
authors.forename: S D
authors.initials: SD
authors.lastname: Anderson
authors.forename: B J
authors.initials: BJ
authors.lastname: Lipworth
mesh_terms: D000085:Acetates; D000249:Adenosine Monophosphate; D000328:Adult; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity; D001985:Bronchial Provocation Tests / Q000379:methods; D016085:Bronchoconstrictor Agents; D018592:Cross-Over Studies; D003521:Cyclopropanes; D004311:Double-Blind Method; D005260:Female; D006634:Histamine H1 Antagonists; D006801:Humans; D020024:Leukotriene Antagonists; D017336:Loratadine / Q000031:analogs & derivatives; D008297:Male; D008353:Mannitol; D008875:Middle Aged; D011804:Quinolines; D013440:Sulfides; D013997:Time Factors
chemical_list: D000085:Acetates; D016085:Bronchoconstrictor Agents; D003521:Cyclopropanes; D006634:Histamine H1 Antagonists; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D008353:Mannitol; D000249:Adenosine Monophosphate; D017336:Loratadine; C121345:desloratadine; C093875:montelukast