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In order to clear airways and lungs defensive reflexes are provoked rather by the dynamic phase of mechanical stimulus. It is speculated that provocation of defensive response depends not only on stimulus duration but also on stimulus velocity. Fourteen adult rabbits were anaesthetized and tracheotomized. Mechanical stimulus was provoked by a mechanical probe introduced through the tracheotomy and rotated by a small electrical motor using a rotational velocity of 40 rpm/s and 20 rpm/s. Threshold, incidence and intensity of cough reflex (CR) were analyzed for each animal. Statistical comparisons between two velocities were performed using Friedman nonparametric test for repeated measurements. Results are median (25-75 %). The threshold of CR was significantly increased (p=0.005) from 350 ms (300-500 ms) to 550 ms (350-1150 ms) and the incidence of cough reflex was significantly reduced (p=0.002) from 50 % (19 50 %) to 0 % (0-25 %) when the rotational velocity of the mechanical probe was reduced by half. The findings of this study are of interest as they show that protective reflex cough, an important mechanism that allows clearing airways even during sleep or anesthesia, is tuned by mechanical stimulus velocity.

Chronic irritating cough in patients with allergic disorders may reflect behavioral or reflex response that is inappropriately matched to the stimulus present in the respiratory tract. Such dysregulated response is likely caused by sensory nerve damage driven by allergic mediators leading to cough hypersensitivity. Some indirect findings suggest that even acid-sensitive, capsaicin-insensitive A-δ fibers called "cough receptors" that are likely responsible for protective reflex cough may be modulated through immune driven inflammation. The aim of this study was to find out whether protective reflex cough is altered during acute allergic airway inflammation in rabbits sensitized to ovalbumin. In order to evaluate the effect of such inflammation exclusively on protective reflex cough, C-fiber mediated cough was silenced using general anesthesia. Cough provocation using citric acid inhalation and mechanical stimulation of trachea was realized in 16 ovalbumin (OVA) sensitized, anesthetized and tracheotomised rabbits 24h after OVA (OVA group, n = 9) or saline challenge (control group, n = 7). Number of coughs provoked by citric acid inhalation did not differ between OVA and control group (12,2 ±6,1 vs. 17,9 ± 6,9; p = 0.5). Allergic airway inflammation induced significant modulation of cough threshold (CT) to mechanical stimulus. Mechanically induced cough reflex in OVA group was either up-regulated (subgroup named "responders" CT: 50 msec (50-50); n = 5 p = 0.003) or down-regulated (subgroup named "non responders", CT: 1200 msec (1200-1200); n = 4 p = 0.001) when compared to control group (CT: 150 msec (75-525)). These results advocate that allergen may induce longer lasting changes of reflex cough pathway, leading to its up- or down-regulation. These findings may be of interest as they suggest that effective therapies for chronic cough in allergic patients should target sensitized component of both, reflex and behavioral cough., Competing Interests: The authors have declared that no competing interests exist.

Lung hyperinflation may alter the pattern of ventilatory reflexes in chronic respiratory disorders. The aim of the study was to test the effect of continuous positive airway pressure (CPAP) on ventilatory responses to mechanical stimulation of the trachea., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Cough 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 & Methods: Ten 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)., Results: Among 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., Conclusion: The 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., Competing Interests: The authors have declared that no competing interests exist.

A link between cough in childhood and neonatal exposure to hyperoxia following preterm birth has been suggested. The hypothesis is tested that neonatal exposure to hyperoxia is associated with long term up regulation of cough. Airway hyperresponsiveness is also investigated because it is a frequent finding in children born preterm and may be linked to cough. Thirty nine young rabbits survived a 48 h neonatal exposure to 93% oxygen (H, n=26) or continued room air (A, n=13). Cough response to mechanical tracheal stimulation and airway responses to a mock exercise and to methacholine were studied under anaesthesia. Larger incidence of coughs and increased sensitivity to tracheal stimulation occurred in H vs A (p<0.01), while bronchial responses to exercise or methacholine were similar in both groups. Neonatal hyperoxia is associated with up regulation of cough in young rabbits. The lack of a parallel increase in airway responsiveness suggests up regulation may be of central origin., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The 'cough center' can be tuned by various afferent inputs, suggesting possible interactions at a central level of neural pathways originating from distant anatomical sites. The present study was designed to determine whether brief mechanical stimulation of the trachea can trigger cough during apnea elicited by nasal instillation of water. Twelve anesthetized, tracheotomized rabbits were studied. Mechanical stimulation of the trachea was performed under 3 conditions: baseline control, after instillation of saline into the nose and during apnea following instillation of water. The baseline breathing pattern did not differ between the 3 conditions. In a series of 171 stimulations, expiration reflex occurred in 81% of stimulations during apnea with a significantly (p<0.0001) lower peak expiratory flow than at baseline or during saline instillation. The incidence of responses comprising a cough reflex was also lower during water instillation than at either baseline or with saline (p<0.0001). These results indicate that stimulation of nasal afferents with distilled water likely down-regulates cough., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objectives: The aim of the study was to characterise mechanically induced cough threshold and reactivity by exposing the trachea to stimuli of variable duration in rabbit., Background: Long lasting mechanical stimulation is widely used in experimental protocols studying cough reflex. The cough threshold and reactivity to chemical agents is known to change due to e.g. airway inflammation but similar evidence for mechanical stimulation has not been reported., Methods: The tracheal provocation was realized in two anesthetized tracheotomized rabbits with a rotating probe actuated by a small electrical motor with mechanical stimulus times (ST) lasting 50, 150, 300 and 600 ms. Cough reflex was evaluated from tidal volume and airflow signals., Results: The incidence of cough reflex (single or multiple) increased from 8% (ST 50 ms) to 84% (ST 600 ms). With the lengthening of stimulus, the rate of multiple responses increases., Conclusion: The technique developed here may prove useful to standardize the protocols of mechanical cough in the experimental animal using an approach similar to chemical tussigenic agents. The cough threshold could be defined as minimal ST (STmin) capable to elicit 1 cough and cough reactivity obtained by interpolation as ST that provokes 50 % of cough responses (STso) (Tab. 1, Fig. 3, Ref. 27).