title: Effect of a novel 5-lipoxygenase activating protein inhibitor, BAYx 1005, on asthma induced by cold dry air.
abstract: BACKGROUND
  Leukotrienes have been implicated in the mediation of airway obstruction induced by hyperventilation of cold dry air in asthmatic subjects. The effect of a novel inhibitor of 5-lipoxygenase activating protein, BAYx 1005, on the bronchospastic response to cold dry air hyperventilation was investigated in asthmatic patients.
  
  
  METHODS
  After a screening cold dry air hyperventilation challenge to document cold air responsiveness, 16 asthmatic subjects (baseline forced expiratory volume in one second (FEV1) > 60% of predicted) underwent cold air challenge three hours after receiving 750 mg of BAYx 1005 or placebo using a randomised, double blind, crossover design. Leukotriene synthesis inhibition was estimated by measuring the concentration of leukotriene B4 in whole blood stimulated with calcium ionophore A21387.
  
  
  RESULTS
  Treatment with BAYx 1005 produced a 34% (95% CI 11 to 63) increase in the amount of cold air minute ventilation required for a 10% decrease in FEV1 (PD10VE) compared with placebo (mean (SE) 37.6 (1.12) 1/min compared with 28.0 (1.13) 1/min, p < 0.006). The PD20VE increased 19% (95% CI 8 to 31) after treatment with BAYx 1005 compared with placebo (57.3(1.10)1/min versus 48.1 (1.10) 1/min, p < 0.002). Treatment with BAYx 1005 produced a 15.4% decrease in ionophore-stimulated LTB4 production, while treatment with placebo produced a 7.1% increase in ex vivo LTB4 (p < 0.02).
  
  
  CONCLUSIONS
  Treatment with BAYx 1005, a novel inhibitor of leukotriene synthesis, produced a significant blunting of cold dry air responsiveness consistent with the hypothesis that leukotrienes mediate part of the bronchoconstriction induced by hyperventilation of cold dry air.
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Fischer
authors.forename: M A
authors.initials: MA
authors.lastname: Rosenberg
authors.forename: M
authors.initials: M
authors.lastname: Roth
authors.forename: M
authors.initials: M
authors.lastname: Loper
authors.forename: S
authors.initials: S
authors.lastname: Jungerwirth
authors.forename: E
authors.initials: E
authors.lastname: Israel
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001249:Asthma / Q000188:drug therapy* / Q000209:etiology; D001985:Bronchial Provocation Tests; D000001:Calcimycin / Q000494:pharmacology; D003080:Cold Temperature / Q000009:adverse effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D007975:Leukotriene B4; D016859:Lipoxygenase Inhibitors / Q000627:therapeutic use*; D008875:Middle Aged; D011804:Quinolines / Q000627:therapeutic use*
chemical_list: D007476:Ionophores; D016859:Lipoxygenase Inhibitors; D011804:Quinolines; C079315:2-(4-(quinolin-2-yl-methoxy)phenyl)-2-cyclopentylacetic acid; D007975:Leukotriene B4; D000001:Calcimycin