{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:44:16Z","timestamp":1790837056421,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T00:00:00Z","timestamp":1614124800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["R01 DC005805"],"award-info":[{"award-number":["R01 DC005805"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Forum Allergy Rhinol"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Multiple hypotheses are evolving that suggest several, potentially overlapping etiologies for olfactory dysfunction (OD) in chronic rhinosinusitis (CRS). Understanding inflammatory cytokine profiles of the olfactory cleft (OC) and their association with olfactory function is foundational for future clinical care and research.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This cross\u2010sectional, case\u2010control study evaluates associations among OC mucus inflammatory proteins, psychophysical olfactory testing, and computed tomography (CT) analysis of the OC and sinuses. Normative reference intervals were determined for each protein and odds ratios (ORs) were used to compare proportions of altered expression between CRS without nasal polyposis (CRSsNP) and CRS without nasal polyposis (CRSwNP).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Case subjects with CRS (n = 151) and controls (n = 74) were evaluated. A majority of OC proteins tested were found within detectable ranges for cases and controls. The CRS cohort had significantly higher concentrations for 23 of 26 proteins. CRS cases with abnormal levels of C\u2010C motif chemokine ligand 2 (CCL2), CCL3, interleukin 5 (IL5), IL10, and IL13 associated with greater olfactory deficits. The prevalence of elevated IL5 and IL13 in anosmic patients was 64.6% and 62.5%, respectively (<jats:italic>p<\/jats:italic> &lt; 0.004). CRS cases with the highest odds of elevated expression in CRSwNP were IL5 (OR = 10.83) and IL13 (OR = 8.36). However, both IL5 and IL13 were still elevated in approximately 14% of CRSsNP patients. The highest magnitude of correlation between the total percent of OC opacification was found to be with IL5 (<jats:italic>r<\/jats:italic> = 0.543; <jats:italic>p<\/jats:italic> &lt; 0.001), whereas other moderate correlations were noted with immunoglobulin E (IgE), IL10, and IL13.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study confirmed that OC inflammatory proteins vary both by disease phenotype and in their association with OD. Type 2 inflammatory mediators are increased in CRS, especially within the CRSwNP group. However, a substantial proportion of CRSsNP also express type 2 inflammatory mediators. Further research is necessary to understand the complex roles OC mucous inflammatory proteins might play in defining endotype and in impacting CRS\u2010related OD. \u00a92021 ARSAAOA, LLC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alr.22770","type":"journal-article","created":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T05:22:36Z","timestamp":1614230556000},"page":"1321-1335","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Olfactory cleft mucus inflammatory proteins in CRS: a case\u2010control study"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6424-7083","authenticated-orcid":false,"given":"Timothy L.","family":"Smith","sequence":"first","affiliation":[{"name":"Division of Rhinology and Sinus\/Skull Base Surgery, Department of Otolaryngology\u2013Head and Neck Surgery Oregon Health &amp; Science University  Portland OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodney J.","family":"Schlosser","sequence":"additional","affiliation":[{"name":"Division of Rhinology and Sinus Surgery, Department of Otolaryngology\u2013Head and Neck Surgery Medical University of South Carolina  Charleston SC"},{"name":"Department of Surgery Ralph H. Johnson VA Medical Center  Charleston SC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary M.","family":"Soler","sequence":"additional","affiliation":[{"name":"Division of Rhinology and Sinus Surgery, Department of Otolaryngology\u2013Head and Neck Surgery Medical University of South Carolina  Charleston SC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jess C.","family":"Mace","sequence":"additional","affiliation":[{"name":"Division of Rhinology and Sinus\/Skull Base Surgery, Department of Otolaryngology\u2013Head and Neck Surgery Oregon Health &amp; Science University  Portland OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8766-1626","authenticated-orcid":false,"given":"Jose L.","family":"Mattos","sequence":"additional","affiliation":[{"name":"Division of Rhinology and Sinus Surgery, Department of Otolaryngology\u2013Head and Neck Surgery University of Virginia  Charlottesville VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2748-0705","authenticated-orcid":false,"given":"Vijay R.","family":"Ramakrishnan","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery University of Colorado\u2010Anschutz Medical Campus  Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8612-5442","authenticated-orcid":false,"given":"Daniel M.","family":"Beswick","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery University of Colorado\u2010Anschutz Medical Campus  Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0560-5028","authenticated-orcid":false,"given":"Jeremiah A.","family":"Alt","sequence":"additional","affiliation":[{"name":"Division of Otolaryngology\u2013Head and Neck Surgery, Department of Surgery University of Utah  Salt Lake City UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer K.","family":"Mulligan","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care &amp; Sleep Medicine University of Florida  Gainesville FL"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.22499"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21994"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.26555"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21711"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1288\/00005537-199407000-00010"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.22391"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.22351"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.02.002"},{"issue":"2","key":"e_1_2_8_10_1","first-page":"S1","article-title":"Clinical practice guideline (update): adult sinusitis","volume":"152","author":"Rosenfeld RM","year":"2015","journal-title":"Otolaryngol Head Neck Surg"},{"key":"e_1_2_8_11_1","first-page":"183","article-title":"Staging in rhinosinusitis","volume":"31","author":"Lund VJ","year":"1993","journal-title":"Rhinology"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.28332"},{"key":"e_1_2_8_13_1","first-page":"222","article-title":"Sniffin\u2019 Sticks\u201d: screening of olfactory performance","volume":"34","author":"Kobal G","year":"1996","journal-title":"Rhinology"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00405-006-0173-0"},{"key":"e_1_2_8_15_1","volume-title":"Sniffin\u2019 Sticks Smell Test Instructions for Use Manual","author":"Burghart Messtechnik","year":"2016"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoto.2016.0927"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1201\/9781482273151"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/33.3.381"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2423(08)60181-X"},{"key":"e_1_2_8_20_1","first-page":"704","article-title":"Determination and validation of reference intervals","volume":"116","author":"Young DS","year":"1992","journal-title":"Arch Pathol Lab Med"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2020.01.014"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.22249"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.27112"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.22633"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.22557"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)31881-1"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.05.032"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02759"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.13502"}],"container-title":["International Forum of Allergy &amp; Rhinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alr.22770","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alr.22770","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alr.22770","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T13:47:41Z","timestamp":1693316861000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/alr.22770"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,24]]},"references-count":28,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2021,9]]}},"alternative-id":["10.1002\/alr.22770"],"URL":"https:\/\/doi.org\/10.1002\/alr.22770","archive":["Portico"],"relation":{},"ISSN":["2042-6976","2042-6984"],"issn-type":[{"value":"2042-6976","type":"print"},{"value":"2042-6984","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,24]]},"assertion":[{"value":"2020-08-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}