Effect of Pressure Stress Applied to the Airway on Cough-Reflex Sensitivity in Guinea Pigs

We hypothesized that cough stress of the airway wall results in a self-perpetuating cough-reflex cycle in which antigen-induced increase in cough-reflex sensitivity results in pathologic cough, and the cough in turn further amplifies cough-reflex sensitivity. To examine cough-reflex sensitivity in an experimental animal model. We developed an experimental guinea pig model in which airway collapse similar to that in cough was induced by rapid negative pressure applied to the airway of artificially ventilated animals. We examined the influence of this stimulus on cough-reflex sensitivity to inhaled capsaicin and bronchoalveolar lavage (BAL) cell components. After the termination of artificial ventilation, the number of coughs due to capsaicin was measured, and BAL was performed. Capsaicin cough-reflex sensitivity and the number of BAL neutrophils were increased 6 hours after stimulus application, decreasing to control levels by 24 hours. Cough-reflex sensitivity or BAL cell components were not changed in the absence of stimulus application. The number of BAL neutrophils correlated significantly with the number of coughs. Hydroxyurea inhibited the stimulus-induced increase in the number of coughs and airway neutrophil accumulation. Our findings suggest that cough itself is a traumatic mechanical stress to the airway wall that induces neutrophilic airway inflammation and cough-reflex hypersensitivity. Cough stress to the airway wall results in a self-perpetuating cough-reflex cycle.