Role of COX-2 in cough reflex sensitivity to inhaled capsaicin in patients with sinobronchial syndrome

The effect of etodolac, a potent COX-2 inhibitor, on cough response to inhaled capsaicin was examined in 15 patients with sinobronchial syndrome 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 < 0.03) increased after two-week treatment with etodolac (200 mg twice a day orally) compared with placebo [37.5 (GSEM 1.3) vs. 27.2 (GSEM 1.3) μM].These findings indicate that COX-2 may be a possible modulator augmenting airway cough reflex sensitivity in patients with sinobronchial syndrome.Chronic productive cough is one of the most common symptoms in patients with sinobronchial syndrome, a common chronic bronchial disorder, which is defined as a coexisting chronic sinusitis and nonspecific chronic neutrophilic inflammation of the lower airways presenting with expectoration (e.g. chronic bronchitis, diffuse bronchiectasis and diffuse panbronchiolitis [1]). Although clinical efficacy for low-dose and long-term erythromycin therapy (EM therapy) has been established in patients with sinobronchial syndrome [2,3], our previous study has shown that 3-6 months are required to improve the cough, sputum and other symptoms [3]. So, it is important to clarify the mechanisms of chronic productive cough to improve social activity in patients suffering sinobronchial syndrome. Previous studies [2-5] implied the involvement of inflammatory mediators in sinobronchial syndrome, however, exact mechanisms underlying cough in this disorder has been remained obscure [3].Cyclooxygenase (COX) is an essential enzyme in the pathway of prostaglandin formation from arachidonic acid. The previous studies [6,7] have revealed the existence of two isoforms of COX, namely COX-1 and COX-2, with similar molecular weights. COX-1 is a constituent of healthy cells and is expressed under normal conditi