Clinical severity and epithelial endotypes in chronic rhinosinusitis

Matthew Lam*, Laura Hull, Rohan Mclachlan, Kornkiat Snidvongs, David Chin, Ellie Pratt, Larry Kalish, Raymond Sacks, Peter Earls, William Sewell, Richard J. Harvey

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    53 Citations (Scopus)

    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. Conclusion: 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.

    Original languageEnglish
    Pages (from-to)121-128
    Number of pages8
    JournalInternational Forum of Allergy and Rhinology
    Volume3
    Issue number2
    DOIs
    Publication statusPublished - Feb 2013

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