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

Abstract

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.

Early exposure to farm dust in an allergic airway inflammation rabbit model: Does it affect bronchial and cough hyperresponsiveness?

“…The mechanical stimulation of the trachea provoked defensive reflexes (DR) that were further discriminated into a cough reflex (CR) and an expiration reflex (ER) according to the change in VT, peak expiratory flow (V'Epeak), and rectus abdominis electromyographic (EMG) activity [23]. The CR was defined by an increase in VT followed by an increase in V'Epeak associated with a burst of rectus abdominis EMG activity (Fig 2 ), and the ER was defined by an increase in V'Epeak without a preceding increase in VT associated with a burst of rectus abdominis EMG activity [24]. To take into account the spontaneous between-breath variability, an unbiased differentiation of the CR and the ER was achieved by a statistical evaluation of the VT between the stimulation and reference breaths.…”