Abstract
BACKGROUND: Recent advances in molecular biology have enabled the identification of potential inflammatory endotypes of chronic rhinosinusitis (CRS), with prior work suggesting differential short-term surgical outcome trajectories based on cytokine signatures. However, there is a paucity of data assessing long-term treatment failure and need for revision surgery based on inflammatory biomarkers. METHODS: Retrospective analysis of prospectively collected cross-sectional data from 231 patients electing surgical therapy for CRS. Intraoperative mucus specimens were quantitatively sampled for inflammatory cytokines using a multiplex flow cytometric bead assay. Univariate Spearman correlations between cytokine levels and prior number of surgeries were assessed. A stepwise adjusted multivariate Poisson regression analysis was used to model patient-reported prior sinus surgery counts as a function of cytokine levels. RESULTS: Several cytokines (interleukin [IL]-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-17A, tumor necrosis factor α [TNF-α], interferon γ [IFN-γ], and eotaxin) demonstrated significant positive correlations with number of prior surgeries. However, only higher IL-17A levels were independently associated with a higher number of prior sinus surgeries (β = 0.345, p = 0.0003) after adjusting for the significant covariates of age (β = 0.018, p = 0.0036), Lund-Mackay score (β = -0.046, p = 0.02), history of aspirin-exacerbated respiratory disease (β = 1.01, p < 0.0001) and allergic fungal rhinosinusitis (β = 1.08, p < 0.0001). Higher levels of regulated on activation, normal T-cell expressed and secreted (RANTES) were conversely associated with a lower number of prior surgeries (β = -0.17, p = 0.048). CONCLUSION: An IL-17A-predominant cytokine profile is linked to an increased number of prior sinus surgeries. Thus, type 3 inflammatory markers may indicate a particularly difficult-to-treat, recalcitrant CRS endotype.