title: Acute neurokinin-1 receptor antagonism fails to dampen airflow limitation or airway eosinophilia in an experimental model of feline asthma.
abstract: OBJECTIVE
  Feline allergic asthma is a chronic inflammatory disorder of the lower airways that may manifest with acute, life-threatening clinical signs. Tachykinins released from sensory nerves and immune cells binding neurokinin (NK)-1, NK-2 and NK-3 receptors have been implicated in asthma pathogenesis. Maropitant, an NK-1 receptor antagonist, blocks neuroimmune pathways and may be a viable treatment option for cats in asthmatic crisis. Using an experimental chronic allergic feline asthma model, we hypothesized that a single dose of maropitant given immediately after allergen challenge would blunt clinical signs, airway hyperresponsiveness (AHR) and airway eosinophilia.
  
  
  METHODS
  Cats (n = 7) induced to have an asthmatic phenotype using Bermuda grass allergen (BGA) were enrolled in a prospective, placebo-controlled crossover design study. Cats randomly received maropitant (2 mg/kg SC) or placebo (saline SC) immediately post-BGA challenge, followed 12 h later by pulmonary mechanics testing and measurement of airway eosinophils. After a 2 week washout, cats were crossed-over to the alternate treatment. Study endpoints included subjective clinical scoring systems post-BGA challenge, ventilator-acquired pulmonary mechanics to assess AHR after bronchoprovocation with methacholine and collection of bronchoalveolar lavage fluid to quantify airway eosinophilia. Data were analyzed using a Mann-Whitney rank sum test with P <0.05 considered significant.
  
  
  RESULTS
  A single injection of maropitant failed to diminish clinical composite score (P = 0.902), visual analogue scale scoring (P = 0.710), AHR (P = 0.456) or airway eosinophilia (P = 0.165) compared with placebo.
  
  
  CONCLUSIONS
  A single injection of maropitant given immediately post-allergen challenge was ineffective at blunting clinical signs, AHR and airway eosinophilia, and cannot be recommended as treatment for feline status asthmaticus.
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: Stacy
authors.initials: S
authors.lastname: Krumme
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: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology / Q000662:veterinary*; D002371:Cat Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology*; D002415:Cats; D018592:Cross-Over Studies; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000188:drug therapy / Q000662:veterinary*; D016233:Immunotherapy, Active / Q000379:methods / Q000662:veterinary*; D011446:Prospective Studies; D011812:Quinuclidines / Q000008:administration & dosage*; D018040:Receptors, Neurokinin-1 / Q000187:drug effects
chemical_list: D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; C518176:maropitant