{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T11:57:05Z","timestamp":1791633425221,"version":"4.3.4"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,11,28]],"date-time":"2018-11-28T00:00:00Z","timestamp":1543363200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["L30 AI113795"],"award-info":[{"award-number":["L30 AI113795"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["RO3 DC014809"],"award-info":[{"award-number":["RO3 DC014809"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006538","name":"School of Medicine, Vanderbilt University","doi-asserted-by":"publisher","award":["P30 AI110527"],"award-info":[{"award-number":["P30 AI110527"]}],"id":[{"id":"10.13039\/100006538","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006538","name":"School of Medicine, Vanderbilt University","doi-asserted-by":"publisher","award":["U19AI095227"],"award-info":[{"award-number":["U19AI095227"]}],"id":[{"id":"10.13039\/100006538","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR000445"],"award-info":[{"award-number":["UL1TR000445"]}],"id":[{"id":"10.13039\/100006108","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":[[2019,3]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Olfactory dysfunction is a common symptom of chronic rhinosinusitis (CRS). We previously identified several cytokines potentially linked to smell loss, potentially supporting an inflammatory etiology for CRS\u2010associated olfactory dysfunction. In the current study we sought to validate patterns of olfactory dysfunction in CRS using hierarchical cluster analysis, machine learning algorithms, and multivariate regression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>CRS patients undergoing functional endoscopic sinus surgery were administered the Smell Identification Test (SIT) preoperatively. Mucus was collected from the middle meatus using an absorbent polyurethane sponge and 17 inflammatory mediators were assessed using a multiplexed flow\u2010cytometric bead assay. Hierarchical cluster analysis was performed to characterize inflammatory patterns and their association with SIT scores. The random forest approach was used to identify cytokines predictive of olfactory function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>One hundred ten patients were enrolled in the study. Hierarchical cluster analysis identified 5 distinct CRS clusters with statistically significant differences in SIT scores observed between individual clusters (<jats:italic>p<\/jats:italic> &lt; 0.001). A majority of anosmic patients were found in a single cluster, which was additionally characterized by nasal polyposis (100%) and a high incidence of allergic fungal rhinosinusitis (50%) and aspirin\u2010exacerbated respiratory disease (AERD) (33%). A random forest approach identified a strong association between olfaction and the cytokines interleukin (IL)\u20105 and IL\u201013. Multivariate modeling identified AERD, computed tomography (CT) score, and IL\u20102 as the variables most predictive of olfactory function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Olfactory dysfunction is associated with specific CRS endotypes characterized by severe nasal polyposis, tissue eosinophilia, and AERD. Mucus IL\u20102 levels, CT score, and AERD were independently associated with smell loss.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alr.22249","type":"journal-article","created":{"date-parts":[[2018,11,28]],"date-time":"2018-11-28T19:00:54Z","timestamp":1543431654000},"page":"255-264","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Patterns of olfactory dysfunction in chronic rhinosinusitis identified by hierarchical cluster analysis and machine learning algorithms"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1777-681X","authenticated-orcid":false,"given":"Justin C.","family":"Morse","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2012Head and Neck Surgery Vanderbilt University Medical Center  Nashville TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan H.","family":"Shilts","sequence":"additional","affiliation":[{"name":"Department of Medicine Vanderbilt University Medical Center  Nashville TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim A.","family":"Ely","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology Vanderbilt University Medical Center  Nashville TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2012Head and Neck Surgery Vanderbilt University Medical Center  Nashville TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanhu","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Vanderbilt University Medical Center  Nashville TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010Ching","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Vanderbilt University Medical Center  Nashville TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd J.","family":"Wannemuehler","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2012Head and Neck Surgery Vanderbilt University Medical Center  Nashville TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naweed I.","family":"Chowdhury","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2012Head and Neck Surgery Vanderbilt University Medical Center  Nashville TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakesh K.","family":"Chandra","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2012Head and Neck Surgery Vanderbilt University Medical Center  Nashville TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suman R.","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Medicine Vanderbilt University Medical Center  Nashville TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin H.","family":"Turner","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2012Head and Neck Surgery Vanderbilt University Medical Center  Nashville TN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,11,28]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajr.2008.22.3195"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.26316"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-200103000-00008"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.22089"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21855"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2010.24.3498"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4507-09.2010"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2010.24.3460"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.24305"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21994"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.27112"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21694_c"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1288\/00005537-198402000-00004"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.02.002"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/alr.22160"},{"key":"e_1_2_6_17_1","first-page":"9","article-title":"A step\u2010by\u2010step approach to using SAS for factor analysis and structural equation modeling' 2nd ed. 2013, SAS Institute Inc., Cary, North Carolina.","author":"O'Rourke N","year":"2013","journal-title":"Anal Struct Model"},{"key":"e_1_2_6_18_1","volume-title":"Factor Analysis","author":"Richard L. 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