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Early attempts to identify CRS endotypes and biomarkers have largely relied on analysis of surgically obtained tissue, thus limiting their practical utility. This study examined the ability of mucus T helper 2 (Th2) biomarkers to predict CRS disease severity and clinical characteristics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>CRS (n = 90) and healthy control subjects (n = 17) were prospectively enrolled prior to surgical intervention and mucus levels of interleukin (IL)\u20104, IL\u20105, and IL\u201013 were determined using a multiplex cytometric bead assay. Data for relevant cytokines was then scaled, normalized, and later combined to develop standardized metrics indicative of Th2\u2010associated inflammation. Th2\u2010high and Th2\u2010low subgroups were consequently identified and validated against factors associated with disease severity and clinical outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mucus levels of IL\u20105 and IL\u201013 were elevated in CRS subjects compared to controls, while no significant difference was noted for IL\u20104. IL\u20105 and IL\u201013 high CRS were associated with worse objective measures of disease severity and greater rates of revision surgery. Similar relationships were noted for both cytokines when CRS with nasal polyps (CRSwNP) patients were analyzed separately. Th2\u2010high CRS and Th2\u2010low CRS were then categorized using a scaled IL\u20105\/IL\u201013 metric. Th2\u2010high CRS was characterized by an increased number of subjects with nasal polyps and comorbid asthma, and worse symptom and computed tomography (CT) scores.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The Th2\u2010associated cytokines, IL\u20105 and IL\u201013, are detectable in sinonasal mucus and their levels can be used to define Th2\u2010high and Th2\u2010low CRS. Identification of Th2\u2010high and Th2\u2010low endotypes using mucus\u2010based biomarkers could facilitate stratification of CRS subgroups and guide personalized therapies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alr.22160","type":"journal-article","created":{"date-parts":[[2018,6,8]],"date-time":"2018-06-08T13:39:26Z","timestamp":1528465166000},"page":"1175-1183","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Mucus T helper 2 biomarkers predict chronic rhinosinusitis disease severity and prior surgical intervention"],"prefix":"10.1002","volume":"8","author":[{"given":"Justin H.","family":"Turner","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Vanderbilt University School of Medicine  Nashville TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Li","sequence":"additional","affiliation":[{"name":"Department of 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