{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:08:18Z","timestamp":1790964498306,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,3,26]],"date-time":"2014-03-26T00:00:00Z","timestamp":1395792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Several chemokines, notably eotaxin, mediate the recruitment of eosinophils into tissues via the <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>3 receptor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>In this study, we investigated the role of <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>3 agonists in asthma by observing the effect of a small molecule antagonist of the <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>3 receptor (<jats:styled-content style=\"fixed-case\">GW<\/jats:styled-content>766994) on sputum eosinophil counts in patients with eosinophilic asthma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical and physiological outcomes, the chemotactic activity of sputum supernatant for eosinophils and the presence of eosinophil progenitors in sputum and blood samples were also studied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In a double\u2010blind parallel group study, 60 patients with asthma were randomized to 300\u00a0mg of <jats:styled-content style=\"fixed-case\">GW<\/jats:styled-content>766994 twice daily or matching placebo for 10\u00a0days followed by prednisone 30\u00a0mg for 5\u00a0days. Of these patients, 53 had a sputum eosinophil count &gt;\u00a04.9% at baseline. Despite plasma concentrations of drug consistent with &gt;\u00a090% receptor occupancy during the dosing period, the <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>3 antagonist did not significantly reduce eosinophils or eosinophil progenitor cells (<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>34<jats:sup>+<\/jats:sup> 45<jats:sup>+<\/jats:sup> <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20105R\u03b1<jats:sup>+<\/jats:sup>) in sputum or in blood. The <jats:italic>ex vivo<\/jats:italic> chemotactic effect of sputum supernatants on eosinophils was attenuated by <jats:styled-content style=\"fixed-case\">GW<\/jats:styled-content>766944 compared to placebo. There was no improvement in <jats:styled-content style=\"fixed-case\">FEV<\/jats:styled-content><jats:sub>1<\/jats:sub>; however, there was a modest but statistically significant improvement in <jats:styled-content style=\"fixed-case\">PC<\/jats:styled-content><jats:sub>20<\/jats:sub> methacholine (0.66 doubling dose) and <jats:styled-content style=\"fixed-case\">ACQ<\/jats:styled-content> scores, (0.43). Whilst the improvement in <jats:styled-content style=\"fixed-case\">PC<\/jats:styled-content><jats:sub>20<\/jats:sub> is statistically significant, it is not of clinical significance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Clinical Relevance<\/jats:title><jats:p>In conclusion, this study calls into question the role of <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>3 in airway eosinophilia in asthma and suggests that other cellular mechanisms mediated by the <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>3 receptor may contribute to airway hyperresponsiveness.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.12244","type":"journal-article","created":{"date-parts":[[2013,11,29]],"date-time":"2013-11-29T04:57:02Z","timestamp":1385701022000},"page":"508-516","source":"Crossref","is-referenced-by-count":87,"title":["Safety and efficacy of an oral <scp>CCR<\/scp>3 antagonist in patients with asthma and eosinophilic bronchitis: a randomized, placebo\u2010controlled clinical trial"],"prefix":"10.1111","volume":"44","author":[{"given":"H.","family":"Neighbour","sequence":"first","affiliation":[{"name":"Division of Respirology McMaster University Hamilton ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.\u2010P.","family":"Boulet","sequence":"additional","affiliation":[{"name":"Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec Qu\u00e9bec QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Lemiere","sequence":"additional","affiliation":[{"name":"Division of Pneumologie University of Montreal Montreal PQ Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Sehmi","sequence":"additional","affiliation":[{"name":"Division of Respirology McMaster University Hamilton ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Leigh","sequence":"additional","affiliation":[{"name":"Division of Respirology University of Calgary Calgary AB Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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