{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T16:29:48Z","timestamp":1787848188315,"version":"build-2784847793"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,5,26]],"date-time":"2016-05-26T00:00:00Z","timestamp":1464220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>In severe asthmatics with persistent airway eosinophilia, blockade of interleukin\u20105 has significant steroid\u2010sparing effects and attenuates blood and sputum eosinophilia. The contribution of local maturational processes of progenitors within the airways relative to the recruitment of mature cells from the peripheral circulation to the development of airway eosinophilia is not known. We hypothesize that local eosinophilopoiesis may be the predominant process that drives persistent airway eosinophilia and corticosteroid requirement in severe asthmatics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>In a cross\u2010sectional study, the number and growth potential of eosinophil\u2010lineage\u2010committed progenitors (EoP) were assayed in 21 severe eosinophilic asthmatics, 19 mild asthmatics, eight <jats:styled-content style=\"fixed-case\">COPD<\/jats:styled-content> patients and eight normal subjects. The effect of anti\u2010<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20105 treatment on mature eosinophils and EoP numbers was made in severe eosinophilic asthmatics who participated in a randomized clinical trial of mepolizumab (substudy of a larger <jats:styled-content style=\"fixed-case\">GSK<\/jats:styled-content> sponsored global phase <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content> trial, <jats:styled-content style=\"fixed-case\">MEA<\/jats:styled-content>115575) where subjects received mepolizumab (100\u00a0mg, <jats:italic>n<\/jats:italic>\u00a0=\u00a09) or placebo (<jats:italic>n<\/jats:italic>\u00a0=\u00a08), as six monthly subcutaneous injections.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mature eosinophil and EoP numbers were significantly greater in the sputum of severe asthmatics compared with all other subject groups. In colony\u2010forming assays, EoP from blood of severe asthmatics demonstrated a greater response to <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20105 than mild asthmatics. Treatment of severe asthmatics with mepolizumab significantly attenuated blood eosinophils and increased EoP numbers consistent with blockade of systemic eosinophilopoiesis. There was however no significant treatment effect on mature eosinophils, sputum EoP numbers or the prednisone maintenance dose.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Clinical Relevance<\/jats:title><jats:p>Patients with severe eosinophilic asthma have an exaggerated eosinophilopoeitic process in their airways. Treatment with 100\u00a0mg subcutaneous mepolizumab significantly attenuated systemic differentiation of eosinophils, but did not suppress local airway eosinophil differentiation to mature cells. Targeting <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20105\u2010driven eosinophil differentiation locally within the lung maybe of relevance for optimal control of airway eosinophilia and asthma.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.12695","type":"journal-article","created":{"date-parts":[[2015,12,19]],"date-time":"2015-12-19T02:44:59Z","timestamp":1450493099000},"page":"793-802","source":"Crossref","is-referenced-by-count":101,"title":["Role of local eosinophilopoietic processes in the development of airway eosinophilia in prednisone\u2010dependent severe asthma"],"prefix":"10.1111","volume":"46","author":[{"given":"R.","family":"Sehmi","sequence":"first","affiliation":[{"name":"Department of Medicine McMaster University and Firestone Institute for Respiratory Health St. Joseph's Healthcare Hamilton ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. G.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Medicine McMaster University and Firestone Institute for Respiratory Health St. Joseph's Healthcare Hamilton ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Kjarsgaard","sequence":"additional","affiliation":[{"name":"Department of Medicine McMaster University and Firestone Institute for Respiratory Health St. Joseph's Healthcare Hamilton ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Radford","sequence":"additional","affiliation":[{"name":"Department of Medicine McMaster University and Firestone Institute for Respiratory Health St. Joseph's Healthcare 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 QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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