title: Effect of pressure stress applied to the airway on cough-reflex sensitivity in Guinea pigs.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Respiratory Medicine, Cellular Transplantation Biology, Kanazawa University Graduate School of Medicine, 13-1, Takara-machi, Kanazawa City, Ishikawa, 920-8641, Japan. hara@ipch.jp
authors.forename: Johsuke
authors.initials: J
authors.lastname: Hara
authors.forename: Masaki
authors.initials: M
authors.lastname: Fujimura
authors.forename: Akihito
authors.initials: A
authors.lastname: Ueda
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Myou
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Oribe
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ohkura
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kita
authors.forename: Masahide
authors.initials: M
authors.lastname: Yasui
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kasahara
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016084:Bronchoconstriction / Q000502:physiology*; D002211:Capsaicin / Q000009:adverse effects; D003371:Cough / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D006918:Hydroxyurea / Q000494:pharmacology; D007249:Inflammation; D007509:Irritants / Q000009:adverse effects; D008297:Male; D009504:Neutrophils / Q000276:immunology; D012018:Reflex / Q000502:physiology*; D012121:Respiration, Artificial / Q000009:adverse effects / Q000379:methods
chemical_list: D004791:Enzyme Inhibitors; D007509:Irritants; D002211:Capsaicin; D006918:Hydroxyurea