{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:58:57Z","timestamp":1790787537918,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008005","name":"Yonsei University College of Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2025,9]]},"abstract":"ABSTRACT<\/jats:title>Background<\/jats:title>As treatment responses differ according to the inflammatory endotype of chronic rhinosinusitis (CRS<\/jats:styled-content>), identifying the endotype could facilitate personalized treatment. We aimed to identify a noninvasive epithelial lining fluid (ELF<\/jats:styled-content>) biomarker for the type 2 (T2<\/jats:styled-content>) endotype of CRS<\/jats:styled-content>.<\/jats:p><\/jats:sec>Methods<\/jats:title>Nasal tissue and ELF<\/jats:styled-content> samples were obtained from patients with CRS<\/jats:styled-content> and control individuals. Single\u2010cell RNA<\/jats:styled-content> sequencing (scRNA<\/jats:styled-content>\u2010seq) data were analyzed. The expression of inflammatory mediators was measured using Luminex multiplex assays and enzyme\u2010linked immunosorbent assays.<\/jats:p><\/jats:sec>Results<\/jats:title>Analysis of the scRNA<\/jats:styled-content>\u2010seq data revealed that CST1<\/jats:italic><\/jats:styled-content> was exclusively expressed in epithelial cells of T2 CRS<\/jats:styled-content>, but not in those of non\u2010T2 CRS<\/jats:styled-content>, and this was confirmed by immunofluorescence staining. Cystatin SN<\/jats:styled-content> expression was detected in ELF<\/jats:styled-content>, and its levels were significantly higher in T2 CRS<\/jats:styled-content> than in non\u2010T2 CRS<\/jats:styled-content> and controls. The expression level of cystatin SN<\/jats:styled-content> in the ELF<\/jats:styled-content> was positively correlated with the Lund\u2010Mackay CT<\/jats:styled-content>, SNOT<\/jats:styled-content>\u201022, and JESREC<\/jats:styled-content> scores, whereas it was inversely correlated with olfactory function. Furthermore, ELF<\/jats:styled-content> cystatin SN<\/jats:styled-content> levels correlated with the tissue\/blood eosinophil count and nasal tissue expression of T2<\/jats:styled-content> inflammatory mediators, indicating that ELF<\/jats:styled-content> cystatin SN<\/jats:styled-content> is a reliable marker of nasal T2<\/jats:styled-content> inflammation. In the receiver operating characteristics curve analysis evaluating the predictive efficacy for T2 CRS<\/jats:styled-content>, the AUC<\/jats:styled-content> for ELF<\/jats:styled-content> cystatin SN<\/jats:styled-content> was 0.894 (0.936 in the validation cohort), which was higher than that of other markers, including blood eosinophil count, serum total IgE<\/jats:styled-content> level, and the JESREC<\/jats:styled-content> score. With a cut\u2010off value of 112.5\u2009ng\/mg, ELF<\/jats:styled-content> cystatin SN<\/jats:styled-content> yielded a 75.0% sensitivity and 92.0% specificity.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>ELF<\/jats:styled-content> cystatin SN<\/jats:styled-content> is a clinically feasible, noninvasive biomarker with superior accuracy for predicting T2 CRS<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.16652","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T12:18:51Z","timestamp":1753100331000},"page":"2572-2585","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Epithelial Lining Fluid Cystatin SN<\/scp> is a Noninvasive Biomarker for Predicting Type 2 Chronic Rhinosinusitis"],"prefix":"10.1111","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6513-0293","authenticated-orcid":false,"given":"Seojin","family":"Moon","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology Yonsei University College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1142-2079","authenticated-orcid":false,"given":"Sungmin","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Yonsei University College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sol","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Yonsei University College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7972-1446","authenticated-orcid":false,"given":"Gyeongyeob","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Yonsei University College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min\u2010Seok","family":"Koo","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Yonsei University College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2851-3225","authenticated-orcid":false,"given":"Hyung\u2010Ju","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Yonsei University College of Medicine Seoul Republic of Korea"},{"name":"The Airway Mucus Institute Yonsei University College of Medicine, Severance Hospital Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1238-6396","authenticated-orcid":false,"given":"Chang\u2010Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Yonsei University College of Medicine Seoul Republic of Korea"},{"name":"The Airway Mucus Institute Yonsei University College of Medicine, Severance Hospital Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1426-7534","authenticated-orcid":false,"given":"Min\u2010Seok","family":"Rha","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Yonsei University College of Medicine Seoul Republic of Korea"},{"name":"The Airway Mucus Institute Yonsei University College of Medicine, Severance Hospital Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2011.02646.x"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-020-00218-1"},{"issue":"29","key":"e_1_2_11_4_1","first-page":"1","article-title":"European Position Paper on Rhinosinusitis and Nasal Polyps 2020","volume":"58","author":"Fokkens W. 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