Elicitation of allergic airway inflammation modulates the cough response via increased prostaglandin I₂ in ovalbumin-sensitized guinea pigs

BACKGROUND: Asthmatic cough is a common cause of chronic cough, and cough-variant asthma (CVA) and typical bronchial asthma (BA) display distinct pathophysiological characteristics. Eosinophilic airway inflammation is believed to contribute to the persistence and treatment resistance of chronic cough, although the underlying mechanisms remain unclear. This study aimed to elucidate the changes in lipid mediators and cough responses induced by eosinophilic airway inflammation. METHODS: We employed an ovalbumin (OVA)-sensitized guinea pig model to investigate the role of eosinophilic airway inflammation and prostaglandinI₂ (PGI₂) in bronchoconstriction-induced cough. Male Hartley guinea pigs were sensitized with OVA and aluminum hydroxide, followed by antigen challenge and methacholine (Mch)-induced bronchoconstriction. Cough responses were recorded, and bronchoalveolar lavage fluid (BALF) was analyzed for inflammatory cell counts and lipid mediator levels. RESULTS: OVA challenge alone increased eosinophil counts without affecting PGI₂, PGE₂, or cysteinyl leukotriene (Cys-LTs) levels. In contrast, Mch inhalation following OVA sensitization and antigen exposure significantly elevated both eosinophils and PGI₂, while cough responses tended to decrease. Cough frequency was negatively correlated with BALF eosinophil counts and positively correlated with the PGE₂/PGI₂ ratio. Administration of a PGI₂ receptor antagonist enhanced cough, whereas a PGI₂ analog suppressed it. CONCLUSIONS: Combined antigen exposure and bronchoconstriction induce PGI₂, which appears to suppress Aδ fiber-mediated cough. These findings underscore the importance of lipid mediator balance in cough regulation and suggest potential therapeutic strategies for asthmatic cough.