Title Role of COX-2 in cough reflex sensitivity to inhaled capsaicin in patientswith sinobronchial syndrome

Background: Sinobronchial syndrome is a cause of chronic productive cough. Inflammatory mediators are involved in the pathophysiology of chronic productive cough. Accumulating evidences indicate that cyclooxygenase (COX)-2, one of the inducible isoforms of COX, is a key element in the pathophysiological process of a number of inflammatory disorders. However, little is known about the role of COX-2 in chronic productive cough in patients with sinobronchial syndrome known as neutrophilic bronchial inflammation. Methods: 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. Results: 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]. Conclusions: These findings indicate that COX-2 may be a possible modulator augmenting airway cough reflex sensitivity in patients with sinobronchial syndrome. Background 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 conditions. On the other hand, COX-2 is highly inducible by a number of stimuli including cytokines and is associated with inflammation. It has been suggested that the induction and regulation of COX-2 may be key elements in the pathophysiological process of a number of inflammation [8]. These findings imply the role of COX-2 in controlling cough reflex sensitivity in sinobronchial syndrome, because cough is one of the major symptoms in this disorder. Our previous study showed that non-specific COX inhibitor, indomethacin, could modulate airway cough reflex sensitivity to inhaled capsaicin [9]. Therefore, we conducted this study in patients * Correspondence: ishiura-@p2322.nsk. ne.jp The Department of Internal Medicine, Toyama City Hospital, Toyama, Japan Full list of author information is available at the end of the article Ishiura et al. Cough 2010, 6:7 http://www.coughjournal. com/content/6/1/7 Cough © 2010 Ishiura et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. with sinobronchial syndrome, using etodolac, proven as a potent COX-2 inhibitor [10,11].