title: Chronic neurokinin-1 receptor antagonism fails to ameliorate clinical signs, airway hyper-responsiveness or airway eosinophilia in an experimental model of feline asthma.
abstract: OBJECTIVE
  Feline allergic asthma is a common chronic lower airway disease characterized by clinical signs attributed to eosinophilic inflammation, airway hyper-responsiveness (AHR) and airway remodeling. Tachykinins released from sensory nerves and immune cells bind neurokinin-1 (NK-1) receptors in the lung. The resultant neurogenic airway inflammation has been implicated in asthma pathogenesis. In mouse models and spontaneous human asthma, NK receptor antagonists reduce bronchospasm and inflammation. We hypothesized that chronic administration of maropitant, an NK-1 receptor antagonist, would decrease clinical signs of asthma, AHR and eosinophilic inflammation in experimentally asthmatic cats.
  
  
  METHODS
  Cats (n = 6) induced to have asthma using Bermuda grass allergen (BGA) were enrolled in a randomized, prospective, placebo-controlled crossover design study. Cats received either oral maropitant (2 mg/kg) or placebo q48h for 4 weeks; following a 2 week washout, cats were crossed-over to the alternate treatment. Study endpoints included subjective clinical scoring systems after BGA challenge, ventilator-acquired pulmonary mechanics to assess AHR after bronchoprovocation with methacholine, and collection of bronchoalveolar lavage fluid to quantify airway eosinophilia. Statistical analysis was performed using a Mann-Whitney rank sum test with P <0.05 considered significant.
  
  
  RESULTS
  Administration of maropitant for 1 month in experimentally asthmatic cats produced no significant difference in clinical scoring scheme (P = 0.589 and P = 1.0), AHR (P = 0.818) or airway eosinophilia (P = 0.669) compared with placebo.
  
  
  CONCLUSIONS
  Chronic administration of maropitant was ineffective at blunting clinical signs, AHR and airway eosinophilia in experimental feline asthma and thus cannot be recommended as a novel treatment for this disorder.
authors.affiliation: Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Grobman
authors.affiliation: Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.
authors.forename: Amber
authors.initials: A
authors.lastname: Graham
authors.affiliation: Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.
authors.forename: Hilton
authors.initials: H
authors.lastname: Outi
authors.affiliation: Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Dodam
authors.affiliation: Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO, USA reineroc@missouri.edu.
authors.forename: Carol R
authors.initials: CR
authors.lastname: Reinero
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000662:veterinary*; D001992:Bronchoalveolar Lavage Fluid; D002371:Cat Diseases / Q000188:drug therapy*; D002415:Cats; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000662:veterinary*; D016210:Methacholine Chloride / Q000008:administration & dosage; D064729:Neurokinin-1 Receptor Antagonists; D011446:Prospective Studies; D011897:Random Allocation; D018040:Receptors, Neurokinin-1
chemical_list: D000485:Allergens; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D016210:Methacholine Chloride