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

Grobman, Megan; Graham, Amber; Outi, Hilton; Dodam, John R.; Reinero, Carol R.

doi:10.1177/1098612x15581406

Cited by 14 publications

(18 citation statements)

References 35 publications

(64 reference statements)

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“…Peripheral actions of NK1‐R are thought to cause vasodilatation, increase vascular permeability and activate airway leukocytes resulting in inflammation and activation of airway sensory afferents . Studies investigating the anti‐inflammatory effects of NK1‐R antagonists have produced variable results . In our study, maropitant had no significant impact on airway inflammation in CCB after 2 weeks of treatment.…”

Section: Discussioncontrasting

confidence: 53%

“…5,10 Studies investigating the anti-inflammatory effects of NK1-R antagonists have produced variable results. 13,14,27 In our study, maropitant a had no significant impact on airway inflammation in CCB after 2 weeks of treatment. There are several reasons why NK1-R antagonism may have been ineffective in ameliorating inflammation associated with CCB.…”

Section: Discussioncontrasting

confidence: 50%

“…NK1 antagonism has been shown to have antitussive effects in a canine model 12 with studies in other species documenting variable effects on airway inflammation. [13][14][15] Maropitant, a a NK-1 receptor antagonist, has been advocated for treatment of CCB based on anecdotal improvement, but without objective supporting evidence. It is critical to determine if perceived efficacy is because of antitussive or anti-inflammatory effects, or both.…”

mentioning

confidence: 99%

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Investigation of Neurokinin‐1 Receptor Antagonism as a Novel Treatment for Chronic Bronchitis in Dogs

Grobman

Reinero

2016

Veterinary Internal Medicne

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BackgroundCanine chronic bronchitis (CCB) results in cough lasting ≥2 months and airway inflammation. Adverse effects include risk of secondary infection associated with lifelong corticosteroid administration and prompt investigation into alternative therapies. Neurogenic pathways mediated by tachykinins that bind neurokinin (NK) 1 receptors may induce cough and airway inflammation. Maropitant,1 a NK‐1 receptor antagonist, has been advocated for treatment of CCB based on anecdotal improvement, but without scientific evidence.Hypothesis/ObjectivesMaropitant1 will blunt clinical signs and airway inflammation associated with CCB.AnimalsClient‐owned dogs (n = 8) with cough >2 months, thoracic radiographic evidence of airway disease and sterile airway inflammation (>7% non‐degenerate neutrophils, >7% eosinophils or both) on bronchoalveolar lavage (BAL) enrolled.MethodsMaropitant1 (2 mg/kg) administered q48h for 14 days. Study endpoints included client perception of clinical signs (surveys at baseline and 14 days, and visual analogue scale [VAS] at baseline, 7, and 14 days), and BAL % neutrophils and eosinophils (baseline and 14 days). One‐way repeated measures ANOVA (VAS) and Wilcoxon‐signed rank‐sum tests (BAL cells, cough frequency) used with P < .05 considered significant.ResultsMaropitant1 significantly decreased cough frequency (P < .001) and VAS scores (P = .005). No differences in BAL % neutrophils or % eosinophils noted with treatment (P = .279 and P = .382, respectively).Conclusions and Clinical ImportancePreliminary results suggest that although maropitant1 may have antitussive properties leading to perceived clinical improvement, its failure to diminish airway inflammation makes it unsuitable for treatment of CCB. Future studies could evaluate maropitant1 as a cough suppressant for other respiratory disorders in dogs.

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Section: Discussioncontrasting

confidence: 53%

Section: Discussioncontrasting

confidence: 50%

mentioning

confidence: 99%

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Investigation of Neurokinin‐1 Receptor Antagonism as a Novel Treatment for Chronic Bronchitis in Dogs

Grobman

Reinero

2016

Veterinary Internal Medicne

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“…Additionally, cats develop spontaneous clinical signs after allergen challenge (cough, wheeze and/or labored breathing on exhalation), BGA-specific IgE and a T helper 2 cytokine profile [ 6 ]. This model is robust and has been used to investigate a variety of relevant clinical therapies including inhibitors of neurogenic inflammation, antihistaminics / antiserotonergics, enantiomers of albuterol, allergen-specific immunotherapy, small molecule inhibitors, and adipose-derived mesenchymal stem cells, among others [ 9 – 14 ]. Since eosinophilic airway inflammation drives airway hyperresponsiveness and remodeling, it is the primary outcome measure evaluated in this model.…”

Section: Introductionmentioning

confidence: 99%

Noninvasive Recognition and Biomarkers of Early Allergic Asthma in Cats Using Multivariate Statistical Analysis of NMR Spectra of Exhaled Breath Condensate

et al. 2016

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Asthma is prevalent in children and cats, and needs means of noninvasive diagnosis. We sought to distinguish noninvasively the differences in 53 cats before and soon after induction of allergic asthma, using NMR spectra of exhaled breath condensate (EBC). Statistical pattern recognition was improved considerably by preprocessing the spectra with probabilistic quotient normalization and glog transformation. Classification of the 106 preprocessed spectra by principal component analysis and partial least squares with discriminant analysis (PLS-DA) appears to be impaired by variances unrelated to eosinophilic asthma. By filtering out confounding variances, orthogonal signal correction (OSC) PLS-DA greatly improved the separation of the healthy and early asthmatic states, attaining 94% specificity and 94% sensitivity in predictions. OSC enhancement of multi-level PLS-DA boosted the specificity of the prediction to 100%. OSC-PLS-DA of the normalized spectra suggest the most promising biomarkers of allergic asthma in cats to include increased acetone, metabolite(s) with overlapped NMR peaks near 5.8 ppm, and a hydroxyphenyl-containing metabolite, as well as decreased phthalate. Acetone is elevated in the EBC of 74% of the cats with early asthma. The noninvasive detection of early experimental asthma, biomarkers in EBC, and metabolic perturbation invite further investigation of the diagnostic potential in humans.

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“…Wochen) des NK1Antagonisten Maropitant (2 mg/ kg) getestet. Die Anwendung hatte in beiden Versuchsansätzen keinen Einfluss auf die Symptomatik, die Atemwegshyperreagibilität oder die eosinophile Entzündung in den Atemwegen[117][118]. Andere, bisher nur experimentell evaluierte Medikamente, die in Ausnahmefällen zur Therapie von felinem Asthma und chronischer Bronchitis zum Einsatz kommen können.…”

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Felines Asthma und chronische Bronchitis – Übersicht zu Diagnostik und Therapie

Grotheer

Schulz²

2019

Tierarztl Prax Ausg K

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ZusammenfassungFelines Asthma und feline chronische Bronchitis gelten als die häufigsten chronischen Erkrankungen der unteren Atemwege bei Katzen und werden oft als chronische Bronchialerkrankungen zusammengefasst. Beim felinen Asthma wird ursächlich eine Hypersensitivitätsreaktion Typ I vermutet, bei der chronischen Bronchitis ist die Ätiologie noch weitgehend unbekannt. Betroffene Katzen können Husten, Dyspnoe und Atemgeräusche zeigen. Beide Krankheitsbilder werden zurzeit anhand des zytologischen Zellbildes einer durch Bronchoalveolarlavage gewonnenen Probe definiert und können sich in Ursache, Behandlung und klinischem Verlauf unterscheiden. Die Diagnosestellung beinhaltet den Ausschluss anderer Grunderkrankungen in Kombination mit dem Nachweis einer nicht infektiösen, eosinophilen oder neutrophilen Entzündung der Atemwege. Neben der etablierten Therapie mit oral oder inhalativ applizierten Glukokortikoiden und Bronchodilatatoren werden in dem Artikel auch neuere therapeutische und diagnostische Ansätze vorgestellt.

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

Abstract: 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.

Cited by 14 publications

References 35 publications

Investigation of Neurokinin‐1 Receptor Antagonism as a Novel Treatment for Chronic Bronchitis in Dogs

Investigation of Neurokinin‐1 Receptor Antagonism as a Novel Treatment for Chronic Bronchitis in Dogs

Noninvasive Recognition and Biomarkers of Early Allergic Asthma in Cats Using Multivariate Statistical Analysis of NMR Spectra of Exhaled Breath Condensate

Felines Asthma und chronische Bronchitis – Übersicht zu Diagnostik und Therapie

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