{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:50:15Z","timestamp":1790974215847,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,3,19]],"date-time":"2015-03-19T00:00:00Z","timestamp":1426723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI49235"],"award-info":[{"award-number":["AI49235"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000871","name":"Mayo Clinic","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The mechanisms and immune pathways associated with chronic rhinosinusitis (<jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>) are not fully understood. Immunological changes during acute exacerbation of <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content> may provide valuable clues to the pathogenesis and perpetuation of the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To characterize local and systemic immune responses associated with acute worsening of sinonasal symptoms during exacerbation in <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content> with nasal polyps (<jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>w<jats:styled-content style=\"fixed-case\">NP<\/jats:styled-content>) compared to controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a non\u2010interventional prospective study of individuals with <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>w<jats:styled-content style=\"fixed-case\">NP<\/jats:styled-content> and normal controls. Subjects underwent a baseline visit with collection of nasal secretions, nasal washes, and serum specimens. Within 3\u00a0days of acute worsening of sinonasal symptoms, subjects underwent a study visit, followed by a post\u2010visit 2\u00a0weeks later. The sinonasal outcome test\u201022 (<jats:styled-content style=\"fixed-case\">SNOT<\/jats:styled-content>\u201022) scores and immunological parameters in the specimens were analysed using a novel, unsupervised learning method and by conventional univariate analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>w<jats:styled-content style=\"fixed-case\">NP<\/jats:styled-content> patients and control subjects showed a significant increase in <jats:styled-content style=\"fixed-case\">SNOT<\/jats:styled-content>\u201022 scores during acute exacerbation. Increased nasal levels of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20105, and eosinophil major basic protein were observed in <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>w<jats:styled-content style=\"fixed-case\">NP<\/jats:styled-content> patients. A network analysis of serum specimens revealed changes in a set of immunological parameters, which are distinctly associated with <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>w<jats:styled-content style=\"fixed-case\">NP<\/jats:styled-content> but not with controls. In particular, systemic increases in <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">GM<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content> levels were notable and were validated by a conventional analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>w<jats:styled-content style=\"fixed-case\">NP<\/jats:styled-content> patients demonstrate distinct immunological changes locally and systemically during acute exacerbation. Growth factors <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">GM<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content> may be involved in the immunopathogenesis of subjects with <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content> and nasal polyps experiencing exacerbation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.12463","type":"journal-article","created":{"date-parts":[[2014,11,28]],"date-time":"2014-11-28T15:57:24Z","timestamp":1417190244000},"page":"767-778","source":"Crossref","is-referenced-by-count":49,"title":["Immunological profiling in chronic rhinosinusitis with nasal polyps reveals distinct <scp>VEGF<\/scp> and <scp>GM<\/scp>\u2010<scp>CSF<\/scp> signatures during symptomatic exacerbations"],"prefix":"10.1111","volume":"45","author":[{"given":"R. D.","family":"Divekar","sequence":"first","affiliation":[{"name":"Division of Allergic Diseases Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Samant","sequence":"additional","affiliation":[{"name":"Department of Allergy Kaiser Permanente Medical Center Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. A.","family":"Rank","sequence":"additional","affiliation":[{"name":"Division of Allergy, Asthma and Clinical Immunology Mayo Clinic Scottsdale AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Hagan","sequence":"additional","affiliation":[{"name":"Division of Allergic Diseases Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Lal","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Mayo Clinic Phoenix AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. K.","family":"O'Brien","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Kita","sequence":"additional","affiliation":[{"name":"Division of Allergic Diseases Mayo Clinic Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,3,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2004.09.029"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2009.23.3355"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.05.022"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2013.27.3850"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-4486.2009.01995.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-4486.2006.01155.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11882-012-0334-8"},{"key":"e_1_2_7_9_1","first-page":"361","article-title":"Gephi: an open source software for exploring and manipulating networks","author":"Bastian M","year":"2009","journal-title":"In Third International AAAI Conference on Weblogs and Social Media"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq430"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq537"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.11.028"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2008.03172.x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1086\/520816"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201103-0585OC"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.10.072"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajr.2008.22.3136"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2006.01225.x"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mlg.0000161334.67977.5D"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2013.06.033"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21116"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21047"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2011.02693.x"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/coa.12132"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201303-047AW"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3003.2000.15b24.x"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2222.1998.00380.x"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-0709(97)90003-X"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.07.049"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003020"}],"container-title":["Clinical &amp; Experimental Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcea.12463","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cea.12463","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T07:43:34Z","timestamp":1696319014000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cea.12463"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3,19]]},"references-count":29,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2015,4]]}},"alternative-id":["10.1111\/cea.12463"],"URL":"https:\/\/doi.org\/10.1111\/cea.12463","archive":["Portico"],"relation":{},"ISSN":["0954-7894","1365-2222"],"issn-type":[{"value":"0954-7894","type":"print"},{"value":"1365-2222","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,19]]}}}