抄録
Eosinophilic airway inflammation and increased cough sensitivity without bronchial hyperresponsiveness are the pathologic and physiologic features of bronchodilator-resistant non-productive cough-associated global atopic tendency, abbreviated herein as atopic cough. Histamine H1 receptor antagonists are effective in relieving the cough in nearly 60% of patients with atopic cough. However, there is no direct evidence that histamine H1 receptor antagonists can reduce cough hypersensitivity associated with eosinophilic airway inflammation. The purpose of the present study was to clarify this issue. The number of coughs caused by inhalation of increasing concentrations of capsaicin (10-8, 10-6 and 10-4 mol/L) was counted 24 h after the administration of an aerosolized antigen in actively sensitized conscious guinea pigs and then bronchoalveolar lavage (BAL) was performed. Azelastine (0.1 or 1 mg/kg) or terfenadine (0.2 or 2 mg/kg) was given intraperitoneally 60 min before capsaicin provocation 24 h after the antigen challenge in sensitized guinea pigs. In addition, azelastine (0.1 or 1 mg/kg) was administered 90 min before the capsaicin challenge in naïve guinea pigs. The cough response to capsaicin and the number of eosinophils in BAL fluid (BALF) were significantly increased after antigen challenge. Azelastine and terfenadine significantly reduced the increased cough response after antigen challenge, while azelastine had no effect in naïve animals. In conclusion, histamine H1 receptor antagonists reduce antigen-induced increases in cough sensitivity in sensitized guinea pigs without direct inhibition of a common cough reflex pathway.
