title: Clinical severity and epithelial endotypes in chronic rhinosinusitis.
abstract: BACKGROUND
  Chronic rhinosinusitis (CRS) is a heterogeneous disease defined by epithelial inflammation. The link between measures of traditional disease severity and markers of epithelial inflammation is poorly understood as prior research has focused on presence of polyps or degree of eosinophilia. The expression of 3 epithelial derived cytokines implicated in initiation of T-helper 2 (Th2) inflammation and an eosinophil chemoattractant were compared with clinical measures used in CRS.
  
  
  METHODS
  Sinus mucosal samples from CRS patients undergoing sinus surgery were analyzed for interleukin-25 (IL-25), IL-33, thymic stromal lymphopoietin (TSLP), and eotaxin-3 messenger RNA (mRNA) expression by quantitative polymerase chain reaction (PCR). Tumor patients undergoing surgery transnasally with normal sinus mucosa were controls. Gene expression was compared with symptom, radiology, and endoscopy scores, serological markers, presence of reactive airways disease (RAD), and atopy.
  
  
  RESULTS
  Thirty-seven patients (38% female, mean age 48 ± 15 years), 12 CRS with nasal polyps (CRSwNP), 18 CRS without nasal polyps (CRSsNP), and 7 controls were recruited. CRSwNP phenotype predicted elevated IL-25, IL-33, and eotaxin-3 levels. Increased eotaxin-3 correlated with poorer computed tomography (CT) (p = 0.004) and endoscopic scores (p = 0.049). Increased IL-25 correlated with poorer CT scores (p = 0.012) and raised serum eosinophils (p = 0.006). No associations with RAD, atopy, and symptom measures were found. No associations for IL-33 and TSLP were found.
  
  
  CONCLUSIONS
  Inflammatory mediators of the epithelium in CRS has some correlation with traditional measures of disease burden. Certain epithelial profiles may predict highly dysfunctional epithelial barriers and prospective evaluation of the clinical outcomes from interventions is required. Future endotyping of the epithelium in CRS may be able to provide prognostic information.
authors.affiliation: St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia. lam.matthew@student.unsw.edu.au
authors.forename: Matthew
authors.initials: M
authors.lastname: Lam
authors.forename: Laura
authors.initials: L
authors.lastname: Hull
authors.forename: Rohan
authors.initials: R
authors.lastname: McLachlan
authors.forename: Kornkiat
authors.initials: K
authors.lastname: Snidvongs
authors.forename: David
authors.initials: D
authors.lastname: Chin
authors.forename: Ellie
authors.initials: E
authors.lastname: Pratt
authors.forename: Larry
authors.initials: L
authors.lastname: Kalish
authors.forename: Raymond
authors.initials: R
authors.lastname: Sacks
authors.forename: Peter
authors.initials: P
authors.lastname: Earls
authors.forename: William
authors.initials: W
authors.lastname: Sewell
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Harvey
mesh_terms: D016022:Case-Control Studies; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000378:metabolism; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D000067596:Interleukin-33; D007378:Interleukins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism*; D009298:Nasal Polyps / Q000276:immunology / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D012220:Rhinitis / Q000276:immunology / Q000378:metabolism*; D012852:Sinusitis / Q000276:immunology / Q000378:metabolism*; D014057:Tomography, X-Ray Computed; D000094632:Thymic Stromal Lymphopoietin
chemical_list: C120429:CCL26 protein, human; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D016207:Cytokines; C506536:IL33 protein, human; D020381:Interleukin-17; D000067596:Interleukin-33; D007378:Interleukins; D012333:RNA, Messenger; D000094632:Thymic Stromal Lymphopoietin