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

¹ Respiratory Medicine, Cellular Transplantation Biology, Kanazawa University Graduate School of Medicine, Kanazawa, Ishikawa, Japan; ² Department of Respiratory Medicine, Ishikawa Prefectural Central Hospital, Kanazawa, Ishikawa, Japan; ³ Department of Internal Medicine, Keiju Medical Center, Nanao, Ishikawa, Japan; and ⁴ Department of Respiratory Medicine, National Hospital Organization Kanazawa Medical Center, Kanazawa, Ishikawa, Japan

Correspondence and requests for reprints should be addressed to Johsuke Hara, M.D., Respiratory Medicine, Cellular Transplantation Biology, Kanazawa University Graduate School of Medicine, 13-1, Takara-machi, Kanazawa City, Ishikawa, 920-8641, Japan. E-mail: hara{at}ipch.jp

Rationale: 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.

Objectives: To examine cough-reflex sensitivity in an experimental animal model.

Methods: 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.

Measurements and Main Results: 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.

Conclusions: 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.

Key Words: cough • cough-reflex sensitivity • hydroxyurea • negative mechanical pressure stress • neutrophilic airway inflammation

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Patients with chronic nonproductive cough usually have enhanced cough-reflex sensitivity to inhaled tussive agents such as capsaicin or citric acid. Little is known about the underlying mechanisms of the increased cough response. What This Study Adds to the Field The cough stress to airway wall may induce a self-perpetuating cough-reflex cycle.