Desensitization of the Cough Reflex Induced by Corticosteroids in Ovalbumin-Sensitized Rabbits During Artificial Limb Exercise.

Simon Valentin,Laurent Foucaud,Delphine Gérard,Bruno Chenuel,Bruno Demoulin,Mathias Poussel,Silvia Demoulin-Alexikova

doi:10.3389/fphys.2020.00466

Simon Valentin, Laurent Foucaud + Show 5 more

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https://doi.org/10.3389/fphys.2020.00466

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Abstract

IntroductionCough is a major symptom frequently experienced during exercise, mainly in asthmatic patients. Inhaled glucocorticoids represent the keystone treatment in the management of asthma, but little is known about interactions between cough and exercise, especially in controlled patients. During exercise, cough reflex (CR) appears downregulated in healthy animal models whereas a lack of desensitization of CR has been shown in ovalbumin-sensitized animal models, mimicking asthmatic disease.Aims and ObjectivesThe goal of our study was to clarify the potential modulation of the CR induced by inhaled corticosteroids (CS) in ovalbumin (OVA) sensitized rabbits during artificial limb exercise.Materials and MethodsSeventeen OVA sensitized rabbits were studied. Among them, 9 were treated with CS delivered intravenously (OVA-Corticoids). The ventilatory response to direct tracheal stimulation, performed at rest and during exercise, was determined to assess the incidence and the sensitivity of the CR. Broncho-alveolar lavage (BAL) and cell counts were performed to determine the level of airway inflammation. Exercise was mimicked by electrically induced hindlimb muscular contractions (EMC).ResultsCompared to rest values, EMC increased minute ventilation by 28% without any decrease in respiratory resistance (Rsr). Among 322 tracheal stimulations, 172 (53%) were performed at rest and 150 (47%) during exercise. The sensitivity of CR decreased during artificial limb exercise compared to baseline in OVA-Corticoids rabbits (p = 0.0313) while it remained unchanged in OVA rabbits (p = NS).ConclusionCorticosteroids appear to restore the desensitization of the CR in OVA sensitized rabbits during artificial limb exercise, suggesting the potential role of airway inflammation in the pathophysiology of cough during exercise in asthmatics.

Highlights

Cough is a major symptom frequently experienced during exercise, mainly in asthmatic patients
Bronchoalveolar Lavage (BAL) fluid count showed no difference in eosinophil (3.1% vs 4.8%) and neutrophil (2.8% vs 3%) cells between the groups
Our animal model allows a discriminant mechanical stimulation during the breathing cycle and we previously show that stimulations occurring during inspiration favor cough reflex (CR) (Varechova et al, 2010), suggesting the importance of the balance of discharge of SARs and rapidly adapting receptors (RARs) during the breathing cycle on the nature of the expulsive event

Summary

Introduction

Cough is a major symptom frequently experienced during exercise, mainly in asthmatic patients. Cough is frequently associated with diseases involving pulmonary eosinophilic inflammation [asthma (Wenzel, 2006), allergy or eosinophilic bronchitis]. Cough can be the unique symptom of asthma, called cough-variant asthma. In these patients, the bronchial wall is mainly infiltrated with eosinophilic cells (Adamko et al, 2003). Physical activity is a major stimulus for asthma symptoms for many patients and cough and bronchoconstriction typically worsens during or after exercise (Parsons et al, 2013). CS are the key treatment in type 2 T helper (Th2) asthma phenotype and more broadly in any respiratory disease that involves eosinophilic inflammation. In exercise-induced bronchoconstriction (EIB), CS are strongly recommended in addition to bronchodilators, resulting in the reduction of symptoms (Poussel and Chenuel, 2010; Parsons et al, 2013)

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