{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T23:35:46Z","timestamp":1773272146382,"version":"3.50.1"},"reference-count":11,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T00:00:00Z","timestamp":1615420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Purpose<\/jats:title>\n<jats:p>To characterize the clinical phenotypes of severe eosinophilic asthma based on early responsiveness to benralizumab in terms of forced expiratory volume in 1 second (FEV<jats:sub>1<\/jats:sub>) improvement.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Patients and methods<\/jats:title>\n<jats:p>Sixty-four participants diagnosed with severe eosinophilic asthma and who had completed 4 months of benralizumab treatment were included in this analysis. Pre-treatment clinical factors were compared between responders and non-responders according to improvements in ACT or FEV<jats:sub>1<\/jats:sub>. Correlations between the sums of increased Type 2-related inflammatory parameters and changes of ACT or FEV<jats:sub>1<\/jats:sub> were also evaluated before and after the 4-month treatment. A two-step cluster analysis was performed to identify distinct phenotypes related to benralizumab responsiveness in terms of FEV<jats:sub>1<\/jats:sub>.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>At the 4-month timepoint, all parameters, except for FeNO, were significantly improved after benralizumab treatment. FEV<jats:sub>1<\/jats:sub> responders were associated with higher levels of Type 2-related inflammatory parameters. An improvement in FEV<jats:sub>1<\/jats:sub> but not in ACT was clearly associated with increases in the sums of increased type 2-related inflammation parameters (p = 0.0001). The cluster analysis identified 5 distinct phenotypes of severe eosinophilic asthma according to the variable FEV<jats:sub>1<\/jats:sub> responsiveness to benralizumab. The greatest response was found in the distinct phenotype of severe eosinophilic asthma, which was characterized by modest increase in total IgE and FeNO relative to blood eosinophils with least exposure to smoking.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>This study, to the best of our knowledge, is the first cluster analysis to report distinct phenotypes related to clinical benralizumab response in a real-world population with severe eosinophilic asthma. These results may help to predict responsiveness to benralizumab in patients with severe eosinophilic asthma.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0248305","type":"journal-article","created":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T18:50:24Z","timestamp":1615488624000},"page":"e0248305","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["Identification of distinct phenotypes related to benralizumab responsiveness in patients with severe eosinophilic asthma"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5489-2062","authenticated-orcid":true,"given":"Hideyasu","family":"Yamada","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayuki","family":"Nakajima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masashi","family":"Matsuyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuko","family":"Morishima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Arai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norihito","family":"Hida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taisuke","family":"Nakaizumi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hironori","family":"Masuko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yohei","family":"Yatagai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takefumi","family":"Saito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuyuki","family":"Hizawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,3,11]]},"reference":[{"key":"pone.0248305.ref001","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1016\/S0140-6736(16)31322-8","article-title":"Benralizumab, an anti-interleukin-5 Receptor \u03b1 Monoclonal Antibody, as Add-On Treatment for Patients With Severe, Uncontrolled, Eosinophilic Asthma (CALIMA): A Randomised, Double-Blind, Placebo-Controlled Phase 3 Trial","volume":"388","author":"J Mark FitzGerald","year":"2016","journal-title":"Lancet"},{"key":"pone.0248305.ref002","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1016\/S0140-6736(16)31324-1","article-title":"Efficacy and Safety of Benralizumab for Patients with Severe Asthma Uncontrolled with High-Dosage Inhaled Corticosteroids and Long-Acting \u03b2 2-agonists (SIROCCO): A Randomised, Multicentre, Placebo-Controlled Phase 3 Trial","volume":"388","author":"R Bleecker Eugene","year":"2016","journal-title":"Lancet"},{"issue":"4","key":"pone.0248305.ref003","doi-asserted-by":"crossref","first-page":"1800936","DOI":"10.1183\/13993003.00936-2018","article-title":"Baseline patient factors impact on the clinical efficacy of benralizumab for severe asthma","volume":"52","author":"Eugene R. 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