Modulation of protective reflex cough by acute immune driven inflammation of lower airways in anesthetized rabbits.

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.

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.

Neonatal hyperoxia up regulates cough reflex in young rabbits.

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.

Airway response to induced muscular contraction in spontaneously breathing rabbits.

The airways are thought to dilate during exercise in humans but the time course and mechanisms of the response are not fully described. The aim of the study was to document changes in airway calibre during electrically induced muscular contractions (MC) in spontaneously breathing rabbits. Experiments were also performed after induced bronchoconstriction to assess the effect of change in breathing pattern on airway calibre during MC. Respiratory resistance (R(RS)) was measured in 12 rabbits using the forced oscillation technique at 20 Hz before, during and after 30s MC in control conditions and after methacholine induced bronchoconstriction (Mch). MC was associated with significant decrease in R(RS) both at control and Mch. The MC induced increase in V(E) occurred with significant albeit small change in mean tidal volume (V(T)) at Mch but not control. An augmented breath (AB) occurred in 29/35 MCs and was usually associated with an abrupt drop in R(RS). The decrease in R(RS) induced by AB was significantly larger at Mch compared with control. Passively inflating the lung after MC induced significantly larger decrease in R(RS) than AB during MC. The data indicate bronchodilation by MC in spontaneously breathing rabbits. The mechanisms appear to include AB dependent airway wall stretching as well as removal of cholinergic input to the airway smooth muscle.

Deep inhalation prevents the respiratory elastance response to methacholine in rats.

The bronchodilator effect of deep inhalation (DI) may be assessed from the time course of respiratory system resistance (Rrs) and reactance (Xrs) measured by the forced oscillation technique at a single frequency. The aim of the study was to assess the effect of DI in the closed chest rat. Under anesthesia and mechanical ventilation, seven Brown Norway rats were given regular DI (BN-di) and six underwent continuous tidal ventilation (BN) throughout an otherwise similar methacholine (Mch) challenge protocol. Rrs and Xrs were monitored at 20 Hz and apparent respiratory system elastance (Ers) was computed from Xrs. After Mch nebulization, there was a significant increase in Rrs and Ers compared with saline. Ers, but not Rrs, decreased after the DI and BN-di were found to have lower Ers than BN. Thus, DI significantly alters Ers and its response to Mch. Computer simulations suggested reversal of increased viscoelasticity and/or inhomogeneous behavior by the DI in that model.