Acute neurokinin-1 receptor antagonism fails to dampen airflow limitation or airway eosinophilia in an experimental model of feline asthma

Abstract

Objectives: 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 and relevance: 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.

Figure 1

(a,b) Seven experimentally asthmatic cats receiving maropitant and placebo in random order were evaluated for clinical signs after allergen challenge using (a) a subjective clinical composite score and (b) a visual analog scale (VAS) score. The boxes represent the 25th and 75th quartiles, with a horizontal line at the median. The whiskers represent the range of the data. The black squares represent the mean. No significant difference was observed between the maropitant or placebo groups based on subjective clinical composite scores or VAS (P = 0.902 and P = 0.710, respectively).

Figure 2

Seven experimentally asthmatic cats receiving maropitant and placebo as part of a randomized, placebo-controlled, prospective, crossover study were evaluated for airway hyperresponsiveness (AHR) following methacholine (MCh) challenge. The boxes represent the 25th and 75th quartiles, with a horizontal line at the median. The whiskers represent the range of the data. The black squares represent the mean. Maropitant did not significantly alter AHR as measured by when the airway resistance exceeded 200% of baseline values (EC200Raw) in response to MCh (P = 0.456). Baseline airway resistance was not significantly different between treatments (P = 0.535)

Figure 3

Seven experimentally induced asthmatic cats receiving maropitant and placebo in random order were evaluated for airway eosinophilia. Bronchoalveolar lavage samples were collected in a blind fashion. A differential count was performed on a Wright’s stained cytospin preparation to evaluate airway eosinophilia (expressed as a percentage of the total cell count identified as eosinophils). The boxes represent the 25th and 75th quartiles, with a horizontal line at the median. The whiskers represent the range of the data. The black squares represent the mean. Maropitant did not significantly decrease airway eosinophilia compared with placebo (P = 0.165)