IL-13 and IL-13–induced periostin levels are specifically decreased in patients following endoscopic sinus surgery for chronic rhinosinusitis

Abstract

BackgroundType 2 (T2) inflammation plays a pathogenic role in chronic rhinosinusitis (CRS) effects of endoscopic sinus surgery (ESS) on T2 inflammation are unknown. ObjectiveTo compare T2 inflammatory biomarkers from middle meatal (MM) mucus for distinguishing CRS from non-CRS patients, identifying major phenotypes (CRS without (CRSsNP) and with nasal polyps (CRSwNP)), assessing endotypic change and establishing cross-sectional and longitudinal outcomes in patients undergoing ESS. MethodsMM mucus samples were collected from CRSsNP and CRSwNP patients before and 6-12 months after ESS and compared to non-CRS control patients. T2 biomarkers were evaluated continuously, using threshold-based definitions of T2 endotype, and for relationships with patient-reported (SNOT-22 and CRS-PRO) and clinician-reported (radiographic and endoscopic) severity. Linear mixed models were developed to analyze clinical variables associated with T2 biomarker levels. Results154 CRS patients (89 CRSsNP, 65 CRSwNP) were enrolled with a mean 9-month interval between ESS and follow-up. Pre-ESS MM mucus analysis revealed elevated T2 mediators in CRSwNP vs. CRSsNP and non-CRS controls. Temporally stable correlations between IL-13 and IL-5; periostin and C5a; and ECP and CCL26 was observed. On this basis and pathologic significance, IL-13, periostin and ECP were further analyzed. Post-ESS, IL-13 and periostin levels decreased significantly, ECP levels remained unchanged. Across pre- and post-ESS evaluation, the T2 endotype was associated with radiographic severity but did not predict outcomes. CRSwNP status and African American race were associated with higher levels of IL-13 and periostin, whereas ECP was higher in patients undergoing extensive surgery. ConclusionESS decreased IL-13 and periostin in MM. T2 inflammation post-ESS correlated with patient- and clinician-reported severity across phenotypes. Pre-ESS T2 inflammation did not predict post-ESS outcomes.