{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T02:32:59Z","timestamp":1772591579761,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,6,4]],"date-time":"2018-06-04T00:00:00Z","timestamp":1528070400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["24249049"],"award-info":[{"award-number":["24249049"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["26461151"],"award-info":[{"award-number":["26461151"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>A predisposition to exacerbations is being recognized as a distinct phenotype with \u201cprevious exacerbations\u201d representing the strongest clinical factor associated with future exacerbation. Thus, to identify additional novel biomarkers associated with asthma exacerbations, \u201cpast exacerbation status\u201d must be included as a confounding factor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aimed to characterize the clinical and biomarker features associated with asthma exacerbations in severe asthma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We evaluated clinical parameters from 105 severe asthmatics yearly for 3\u00a0years, as well as their exacerbation status. We classified the subjects into 3 groups: (i) consistent non\u2010exacerbators (<jats:styled-content style=\"fixed-case\">CNE<\/jats:styled-content>, subjects who did not experience any exacerbation over the 3\u2010year period); (ii) consistent frequent exacerbators (<jats:styled-content style=\"fixed-case\">CFE<\/jats:styled-content>, subjects with frequent exacerbation, defined as those who had 2 or more exacerbations within 1\u00a0year, throughout the 3\u2010year period); and (iii) intermittent exacerbators (<jats:styled-content style=\"fixed-case\">IE<\/jats:styled-content>). We conducted multivariate analysis for comparisons among the groups for multiple factors, including several Th2\u2010related biomarkers, in addition to the \u201cpast exacerbation status.\u201d<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty\u2010nine subjects were classified as <jats:styled-content style=\"fixed-case\">CNE<\/jats:styled-content>, 15 as <jats:styled-content style=\"fixed-case\">CFE<\/jats:styled-content>, and 51 as <jats:styled-content style=\"fixed-case\">IE<\/jats:styled-content>. Frequent exacerbations in the previous year predicted exacerbations for the following year (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001). Among the several Th2\u2010related biomarkers, only Fe<jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content> was associated with exacerbation status. When we analysed the data after the second visit, the impact of Fe<jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content> on predicting future exacerbation remained significant, even after considering the exacerbation status during the first year (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Clinical Relevance<\/jats:title><jats:p>Measurement of Fe<jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content> has a significant potential to predict future asthma exacerbation, which is independent of the \u201cpast exacerbation history.\u201d<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.13170","type":"journal-article","created":{"date-parts":[[2018,5,21]],"date-time":"2018-05-21T11:29:36Z","timestamp":1526902176000},"page":"1137-1146","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Prospective predictors of exacerbation status in severe asthma over a 3\u2010year follow\u2010up"],"prefix":"10.1111","volume":"48","author":[{"given":"H.","family":"Kimura","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine Faculty of Medicine and Graduate School of Medicine Hokkaido University Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6439-2443","authenticated-orcid":false,"given":"S.","family":"Konno","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Faculty of Medicine and Graduate School of Medicine Hokkaido University Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Makita","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Faculty of Medicine and Graduate School of Medicine Hokkaido University Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Taniguchi","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Faculty of Medicine and Graduate School of Medicine Hokkaido University Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Faculty of Medicine and Graduate School of Medicine Hokkaido University Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Faculty of Medicine and Graduate School of Medicine Hokkaido University Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Faculty of Medicine and Graduate School of Medicine Hokkaido University Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Goudarzi","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Faculty of Medicine and Graduate School of Medicine Hokkaido University Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Nakamaru","sequence":"additional","affiliation":[{"name":"Otolaryngology Head and Neck Surgery Hokkaido University School of Medicine Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Ono","sequence":"additional","affiliation":[{"name":"Shino\u2010Test Corporation Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Ohta","sequence":"additional","affiliation":[{"name":"Division of Medical Biochemistry Department of Biomolecular Sciences Saga Medical School Saga Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Izuhara","sequence":"additional","affiliation":[{"name":"Division of Medical Biochemistry Department of Biomolecular Sciences Saga Medical School Saga Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.\u00a0M.","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Faculty of Medicine and Graduate School of Medicine Hokkaido University Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. 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