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Currently, vascular and matrix airway remodeling in asthma with neutrophilic\/mixed inflammation is not well known. We aimed to evaluate the differences in vascular\/smooth muscle\/matrix related asthma remodeling in eosinophilic (EOS) and mixed\/neutrophilic (MIXED) bronchial phenotypes in relation to asthma severity and exacerbation frequency.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>In this cross-sectional study, \u03b1-SMA<jats:sup>+<\/jats:sup> cells (100\u00b5M beneath the basement membrane [BM]), BM thickness, vascular remodeling-related biomarkers (angiogenin, vascular endothelial growth factor [VEGF], CD31 and Protease-activated receptor 2 [PAR2]), alarmins (TSLP and Interleukin (IL)-33) were evaluated in bronchial sections from 40 mild-to-severe asthmatics (EOS: <jats:italic>N<\/jats:italic>\u2009=\u200919 and mixed\/neutrophilic: <jats:italic>N<\/jats:italic>\u2009=\u200919\/2) and 7 control subjects (CTRL).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The number of CD31<jats:sup>+<\/jats:sup> and angiogenin<jats:sup>+<\/jats:sup> cells was higher in MIXED than in EOS asthmatics (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). In severe MIXED CD31<jats:sup>+<\/jats:sup>, TSLP<jats:sup>+<\/jats:sup>, \u03b1-SMA<jats:sup>+<\/jats:sup>, and angiogenin<jats:sup>+<\/jats:sup> cells increased compared to mild MIXED\/EOS or severe EOS (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), but BM thickness was higher in severe vs. mild EOS (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). MIXED frequent exacerbators had higher numbers of CD31<jats:sup>+<\/jats:sup> and TSLP<jats:sup>+<\/jats:sup> cells, whereas MIXED non-exacerbators had increased PAR2<jats:sup>+<\/jats:sup> cells. CD31<jats:sup>+<\/jats:sup> cells correlated with impairment of pulmonary functions, number of exacerbations, ICS dose, bronchial neutrophils, angiogenin, \u03b1-SMA, TSLP and IL-33 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Finally, CD31\u2009&gt;\u200997.17 cells\/mm<jats:sup>2<\/jats:sup>, angiogenin\u2009&gt;\u200935.36 cells\/mm<jats:sup>2<\/jats:sup>, and functional parameters such as FEV<jats:sub>1<\/jats:sub>, FEV<jats:sub>1<\/jats:sub>\/FVC, TLC and FRC (%pred.) were found to be predictors of severe MIXED asthma.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>The severe or frequent exacerbator asthmatics with bronchial mixed inflammatory profile are characterized by increased number of vessels and overexpression of TSLP and angiogenin, suggesting a pathogenetic link between mixed eosinophilic and neutrophilic inflammation and vascular remodeling.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12931-025-03133-9","type":"journal-article","created":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T18:37:01Z","timestamp":1740767821000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Vascular remodeling and TSLP\/angiogenin overexpression in severe mixed asthma"],"prefix":"10.1186","volume":"26","author":[{"given":"Francesca","family":"Bertolini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitina M.A.","family":"Carriero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Arrigo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Guida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Levra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Pizzimenti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirella","family":"Profita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Gnemmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Di Stefano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio L.M.","family":"Ricciardolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,28]]},"reference":[{"key":"3133_CR1","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1136\/thoraxjnl-2012-202741","volume":"68","author":"FL Ricciardolo","year":"2013","unstructured":"Ricciardolo FL, Sabatini F, Sorbello V, Benedetto S, Defilippi I, Petecchia L, et al. 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The San Luigi Gonzaga University Hospital Ethical Review Board approved the study (protocol numbers: 1759\/2008 and 14871\/2009) in accordance with the Declaration of Helsinki. Informed consent was obtained from all subjects involved in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Informed written consent and approval for publication in anonymous form was released by all patients.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Clinical trial number"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"78"}}