Bruno Demoulin

Nasal stimulation by water down-regulates cough in anesthetized rabbits

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.

Stimulus response latency of cough and expiration reflex depends on breathing in the rabbit.

Expiration reflex and cough may have distinct afferent pathways and/or central integrative mechanisms that may both result in different stimulus response latencies. A newly described method that uses a punctuate mechanical tracheal stimulus to provoke defensive ventilatory reflexes should allow the stimulus response latency to be calculated with reasonable accuracy. The aim of the study was to test whether cough and expiration reflex have different stimulus response latencies. Four hundred and sixty one mechanical tracheal stimulations (50-300 msec) were performed in 21 anesthetized, tracheotomized rabbits. Twenty three percent stimulations (108) provoked a cough reflex and 37% an expiration reflex (171). The individual mean stimulus response latency was computed for each reflex, calculated from stimulus onset to earliest detectable change in ventilatory flow. Cough reflex latency was significantly shorter in inspiration compared to expiration (257±19 msec vs 391±61 msec; p=0.01). In contrast, the expiration reflex latency was significantly shorter in expiration compared to inspiration (210±11 msec vs 329±29 msec, p=0.003). It is concluded that the within breath dependence of the difference in stimulus response latency between cough and expiration reflex is more likely to express different brainstem mechanisms but difference in afferent fibres may not be excluded.

Desensitization of the cough reflex during limb muscle contraction in anesthetized rabbits

The cough network exhibits plasticity at the sensor and integration levels leading to modulation of the strength or pattern of the cough reflex. Little is known about the interactions between cough and human activities, especially during exercise. The present study was designed to determine whether exercise, mimicked by electrically induced muscle contractions, can modify the incidence and/or strength of cough following mechanical stimulation of the trachea in anesthetized rabbits. Thirteen anesthetized, tracheotomized rabbits were studied by a total of 311 tracheal stimulations: 196 at rest and 115 during exercise. During muscle contractions, the incidence of the cough reflex (CR) decreased and the expiration reflex (ER) increased (p < 0.0001). The sensitivity of the CR and ER both decreased during exercise compared to the sensitivity of the CR at rest (p < 0.02), while the strength of the expulsive response remained unchanged. These results indicate that adjustments occurring during muscle contractions likely downregulate tracheal defensive reflexes in anesthetized rabbits.

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

Cough is typically associated with physical activity in children with asthma, but the characteristics of the relationship between cough and exercise has not been established under physiological conditions. The aim of the study was to describe the effect of exercise on the reflex cough response elicited by a single breath of capsaicin in non-asthmatic children. A group of non-asthmatic adults was studied as reference. Thirty children and 29 adults were recruited. The cough reflex sensitivity to capsaicin was first determined to establish the dose that provokes 5 cough efforts (C5). The number of coughs elicited by C5 (NC5) was then compared at baseline and during a standardized submaximal treadmill exercise. Data are expressed as median (interquartile range). Children and adults showed a significant decrease in NC5 (respectively from 5.0 (4.0–6.0) to 2.5 (2.0–4.0), p < 0.0005 and from 6.0 (5.0–7.0) to 2.0 (0.0–3.0, p < 0.0005). During exercise, NC5 was observed to decrease in all adult subjects, but in only 24/30 children (80%, p = 0.02). A trend for a higher incidence of personal and familial atopy was observed in children that lacked cough down-regulation during exercise compared with other children. It is concluded that the cough reflex response to capsaicin is down regulated by exercise in both children and adults. The effect however is less consistently observed in the former. The difference may reflect maturation of descending inhibitory pathways of the cough reflex, but may also be associated to atopy. The data stress the importance of assessing the time relationship of cough and exercise in questionnaire studies of asthma.

Breathing‐related changes of respiratory resistance in vocal cord dysfunction

Vocal cord dysfunction induced by exercise in children with uncontrolled asthma was identified by laryngoscopy. The paradoxical adduction of the vocal cords was also indicated by the breathing‐related changes of the forced oscillation respiratory resistance showing prominent increase during inspiration and a large positive difference between inspiration and expiration. The breathing‐related changes of respiratory resistance offer thus a useful first‐line technique to diagnose vocal cord dysfunction.

Epinephrine but not vasopressin attenuates the airway response to anaphylactic shock in rats

ABSTRACT Purpose: The two life-threatening signs of anaphylactic shock (AS) are severe arterial hypotension and bronchospasm. Guidelines recommend epinephrine as first-line treatment. Arginine vasopressin (AVP) has been proposed as an alternative if epinephrine does not correct arterial hypotension. These two drugs may have beneficial, neutral or deleterious effects on airflow either directly or by modifying factors that regulate vasodilatation and/or edema in the bronchial wall. Aim of the Study: To compare the effects of epinephrine and AVP on airflow and airway leakage in a rat model of AS. Materials and Methods: Thirty-two ovalbumin-sensitized rats were randomized into four groups: control (CON), AS without treatment (OVA), AS treated with epinephrine (EPI), and AS treated with AVP (AVP). Mean arterial pressure (MAP), respiratory resistance and elastance and microvascular leakage in the airways were measured. Results: All OVA rats died within 20 minutes following ovalbumin injection. Ovalbumin induced severe arterial hypotension and airway obstruction (221 ± 36 hPa.s.L−1 vs. vehicle 52 ± 8 hPa.s.L−1; p < 0.0001) associated with microvascular leakage distributed throughout the trachea, bronchi and intra-pulmonary airways. EPI and AVP extended survival time; EPI restored a higher level of MAP than AVP. Airway obstruction was attenuated by epinephrine (146 ± 19 hPa.s.L−1; p < 0.0001), but not by AVP (235 ± 58 hPa.s.L−1; p = 0.42). Conclusions: Epinephrine was superior to AVP for alleviating the airway response in a rat model of AS. When bronchospasm and severe arterial hypotension are present during AS, epinephrine should be the drug of choice.

Biphasic airway–lung response to anaphylactic shock in Brown Norway rats

Bronchospasm may be part of the response to systemic anaphylaxis in humans. The anaphylactic shock has been characterized in allergic rats, but little data are available on the concurrent changes in airway-lung mechanics. The aim was to describe the respiratory resistance (Rrs) and reactance (Xrs) response to ovalbumin (OVA) induced systemic anaphylaxis in allergic rats. Thirty five anesthetized and mechanically ventilated Brown Norway rats were randomly allocated to OVA (n=20) or vehicle (n=15) sensitization and provocation. Rrs and Xrs were obtained by the forced oscillation technique at 20 Hz. Allergic rats showed dramatic and reproducible concurrent Rrs peak and Xrs through within 4 min of OVA injection (p<0.0001). Thereafter, Rrs returned to baseline while Xrs remained significantly more negative (p<0.0001). It is concluded that systemic anaphylaxis in allergic rats is associated with severe early acute inhomogeneous bronchoconstriction followed by pulmonary interstitial/small airspace edema. The model may be of interest to assess treatments targeting the associated bronchoconstriction and/or airway vascular leakage.

Modulation of defensive airway reflexes during continuous positive airway pressure in the rabbit

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.

Maturation of Airway Defensive Reflexes Is Related to Development of Feeding Behavior during Growth in Rabbits

Introduction: Cough and expiration reflex are major lower airway defense mechanisms that have not been studied throughout development in relation with the feeding behavior. Aim: To describe airway defense reflexes evoked by mechanical stimulation of the trachea in developing rabbit pups. Material and Methods: Sixty one pups were allocated to 3 groups according to their feeding behavior: suckling (n = 22), weanling (n = 21) and weaning (n = 18) group. The incidence and sensitivity of defense reflexes triggered by mechanical tracheal stimulation were studied in anesthetized and tracheotomized animals. Data are expressed as median (25th to 75th percentile). Results: The overall incidence of defensive responses (cough and/or expiration reflex) was found to be significantly higher in suckling [100% (50–100%); p = 0.01] and weanling [75% (40–100%); p = 0.05] animals when compared to weaning ones [37.5% (0–75%)]. However, cough motor pattern accounted for only 29% (0–62%) of all defensive responses in suckling rabbits and its frequency was significantly lower in this group when compared with weanling [100%(50–100%); p = 0.006] or weaning group [62%(50–100%), p = 0.05]. In other word the expiration reflex was the dominant response in suckling animals. Conclusion: Incidence and motor pattern of defensive responses were found to be linked to the pup feeding behavior and the expiration reflex was the major response triggered in suckling pups. The results suggest that this reflex is especially fitted to occur during the coordinated swallowing - breathing fast activities of sucking.

Specific airway resistance in healthy young Vietnamese and Caucasian adults

In healthy Vietnamese children the respiratory resistance has been suggested to be similar at 110 cm height but larger at 130 cm when compared with data in Caucasians from the literature, suggesting smaller airways in older Vietnamese children (Vu et al., 2008). The hypothesis tested here is whether the difference in airway resistance remains consistent throughout growth, and if it is larger in adult Vietnamese than in Caucasians. Airway resistance and Functional Residual Capacity were measured in healthy young Caucasian and Vietnamese adults in their respective native country using identical equipment and protocols. Ninety five subjects in Vietnam (60 males) and 101 in France (41 males) were recruited. Airway resistance was significantly larger in Vietnamese than in Caucasians and in females than in males, consistent with difference in body dimensions. Specific airway resistance however was not different by ethnicity or gender. The findings do not support the hypothesis that airway size at adult age - once normalized for lung volume - differs between Vietnamese and Caucasians.