American Journal of Respiratory Cell and Molecular Biology vol:44 issue:4 pages:517-523
Rationale: Although the concept of âglobal airway allergyâ has become widely accepted during recent years, nasobronchial interaction and its mechanisms remain incompletely understood. The experimental study of the effect of nasal allergen deposition on lower airway pathology is hampered by the difficulty to avoid lower airway penetration of the allergens. Methods: In ovalbumin-sensitized mice with experimental airway allergy, nasal allergen provocations were performed after complete anatomical separation of upper and lower airways by means of a tracheotomy. A canula was inserted in the trachea and the trachea was ligated, thus inhibiting any passage of allergens from upper to lower airways. Results: Mice showed bronchial hyperresponsiveness to methacholine as early as 4 h after nasal allergen provocation in the absence of recruitment of inflammatory cells. An increased substance P concentration in the bronchial lumen was found, as well as an increased number of substance P-positive pulmonary nerves. Treatment with a neurokinin 1 receptor antagonist abolished the allergen-induced bronchial hyperresponsiveness. Moreover, endobronchial administration of substance P caused neurokinin 1 receptor-dependent bronchial hyperresponsiveness in mice with airway allergy. Conclusions: Nasal allergen provocation rapidly induces bronchial hyperresponsiveness via pulmonary upregulation of substance P and activation of NK 1 receptors.