Chronic neurokinin-1 receptor antagonism fails to ameliorate clinical signs, airway hyper-responsiveness or airway eosinophilia in an experimental model of feline asthma.

Abstract

OBJECTIVES: 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 AND RELEVANCE: 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.