Prostaglandin I2 enhances cough reflex sensitivity to capsaicin in the asthmatic airway

Abstract

Inflammatory mediators are involved in the pathogenesis of airway inflammation, but the role of prostaglandin I2 (PGI2) remains obscure. This study was designed to investigate the role of PGI2 in cough reflex sensitivity of the asthmatic airway, which is characterized by chronic eosinophilic airway inflammation. The effect of beraprost, a chemically and biologically stable analogue of PGI2, on cough response to inhaled capsaicin was examined in 21 patients with stable asthma in a randomized, placebo-controlled cross over study. Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough reflex sensitivity. The cough threshold was significantly (p < 0.05) decreased after two weeks of treatment with beraprost [17.8 (GSEM 1.20) microM] compared with placebo [30.3 (GSEM 1.21) microM]. PGI2 increases cough reflex sensitivity of the asthmatic airway, suggesting that inhibition of PGI2 may be a novel therapeutic option for patients with asthma, especially cough predominant asthma.

Figure 1

Study protocol.

Figure 2

Individual data of capsaicin cough threshold at run-in period, at washout period and on treatment with beraprost and placebo in patients with stable bronchial asthma. Each horizontal bar represents geometric mean value. Closed circles and open circles represent patients undergoing steroid inhalation therapy and patients without steroid inhalation therapy, respectively. P values: Wilcoxon signed-ranks test using logarithmically transformed values.

Figure 3

Individual data of serum IgE at run-in period, at washout period and on treatment with beraprost and placebo in patients with stable bronchial asthma. Each horizontal bar represents geometric mean value. Closed circles and open circles represent patients undergoing steroid inhalation therapy and patients without steroid inhalation therapy, respectively. P values: Wilcoxon signed-ranks test using logarithmically transformed values.

Figure 4

Individual data of peripheral blood eosinophils at run-in period, at washout period and on treatment with beraprost and placebo in patients with stable bronchial asthma. Each horizontal bar represents geometric mean value. P values: Wilcoxon signed-ranks test.