Lack of desensitization of the cough reflex in ovalbumin-sensitized rabbits during exercise

Abstract

IntroductionCough is a major symptom of asthma frequently experienced during exercise but little is known about interactions between cough and exercise. The goal of our study was to clarify the potential modulation of the cough reflex (CR) by exercise in a spontaneously breathing anaesthetized animal model of airway eosinophilic inflammation.Materials & methodsTen ovalbumin (OVA) sensitized adult rabbits and 8 controls were studied. The ventilatory response to direct tracheal stimulation, performed both at rest and during exercise was determined to quantify the incidence and the sensitivity of the CR.Broncho-alveolar lavages (BAL) and cell counts were performed to assess the level of the airway inflammation following OVA-induced sensitization. Exercise was mimicked by Electrically induced hindlimb Muscular Contractions (EMC).ResultsAmong 494 tracheal stimulations, 261 were performed at rest and 233 at exercise. OVA challenges in sensitized rabbits caused a significant increase in the percentage of eosinophils (p = 0.008) in BAL. EMC increased minute ventilation by 36% and 35% in OVA and control rabbits respectively, compared to rest values. The sensitivity of the CR decreased during exercise compared to baseline in control rabbits (p = 0.0313) while it remained unchanged in OVA rabbits.ConclusionThe desensitization of the CR during exercise in control rabbits was abolished in OVA rabbits. The precise role of airway inflammation in this lack of CR desensitization needs to be further investigated but it might contribute to the exercise-induced cough in asthmatics.

Brainstem mechanisms underlying the cough reflex and its regulation

“…Central and peripheral mechanisms involved in exercise and voluntary isocapnic hyperventilation may downregulate the cough response (Lavorini et al, 2010;Poussel et al, 2014). However, exercise (electrically induced hindlimb muscular contractions) in ovalbumin-sensitized rabbits fails to produce similar effects (Tiotiu et al, 2017). An important characteristic of the cough reflex is its very strong dependency on the sleep-wakefulness state as well as on anesthesia (Nishino et al, 1988;Widdicombe and Singh 2006).…”

Down-Regulation of Cough during Exercise Is Less Frequent in Healthy Children than Adults. Role of the Development and/or Atopy?

“…Exercise appears to modulate cough reflex response in a similar way as it does for the bronchomotor tone. Clinical studies in normal and asthmatic subjects and animal models of asthma have demonstrated airway dilation (Lee and Anderson, 1985 ; Cabral et al, 1999 ) and/or cough suppression (Lavorini et al, 2010 ; Tiotiu et al, 2017 ) during exercise while a transient airway narrowing (Lee and Anderson, 1985 ; Cabral et al, 1999 ; Anderson and Daviskas, 2000 ) and cough induction that occurs several minutes after exercise cessation is frequently seen in asthmatic subjects or athletes (Powell et al, 1996 ; Turmel et al, 2012 ; Bordeleau et al, 2014 ).…”

“…The mechanisms by which the physiologic adaptation can be altered has not been widely studied, however the association with airway inflammation is highly suggested (Hazucha et al, 1996 ). A recent demonstration of lack of cough down-regulation during electrical limb muscle stimulation in a rabbit model of late-phase response to allergen inhalation (Tiotiu et al, 2017 ) suggested a role for eosinophilic inflammation. A few studies conducted among high-level athletes showed a higher prevalence of cough during prolonged exercise or when performed under specific environmental conditions (Turmel et al, 2012 ; Boulet et al, 2017 ).…”

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

“…As previously described (Tiotiu et al, 2017), rabbits were sensitized the month before the acute experiment (performed on day 29 on the trial calendar) according to the following protocol:…”

“…Previous studies have proven that CR is decreased during exercise in healthy subjects (Lavorini et al, 2010;Demoulin-Alexikova et al, 2017) as well as in animal models (Poussel et al, 2014), even the precise underlying mechanisms are still debated. In contrast, CR sensitivity during exercise was unchanged (i.e., lack of downregulation) in ovalbumin (OVA)-sensitized rabbits (eosinophilic bronchial inflammation mimicking classical asthmatic inflammation) (Tiotiu et al, 2017), suggesting the contribution of bronchial eosinophilic inflammation in the modulation of CR in asthmatics during exercise.…”