Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
Int Forum Allergy Rhinol. 2021 Feb;11(2):120-127. doi: 10.1002/alr.22652. Epub 2020 Jul 23.
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.
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.
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).
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.
分子生物学的最新进展使人们能够鉴定慢性鼻-鼻窦炎（CRS）的潜在炎症内型，先前的工作表明基于细胞因子特征存在不同的短期手术结果轨迹。然而，基于炎症生物标志物评估长期治疗失败和需要修正手术的数据很少。
对 231 例选择手术治疗 CRS 的患者前瞻性收集的横断面数据进行回顾性分析。使用多重流式细胞术检测分析对术中粘液标本进行炎症细胞因子的定量取样。评估细胞因子水平与先前手术次数之间的单变量斯皮尔曼相关性。采用逐步调整多元泊松回归分析，将患者报告的先前鼻窦手术次数作为细胞因子水平的函数进行建模。
几种细胞因子（白细胞介素[IL]-1β、IL-4、IL-5、IL-6、IL-8、IL-10、IL-13、IL-17A、肿瘤坏死因子α[TNF-α]、干扰素γ[IFN-γ]和嗜酸性粒细胞趋化因子）与先前手术次数呈显著正相关。然而，仅较高的 IL-17A 水平与较高的先前鼻窦手术次数独立相关（β=0.345，p=0.0003），调整年龄（β=0.018，p=0.0036）、Lund-Mackay 评分（β=-0.046，p=0.02）、阿司匹林加重性呼吸道疾病史（β=1.01，p＜0.0001）和变应性真菌性鼻-鼻窦炎（β=1.08，p＜0.0001）等显著协变量后。调节激活正常 T 细胞表达和分泌的细胞因子（RANTES）水平则相反与先前手术次数减少相关（β=-0.17，p=0.048）。
IL-17A 优势细胞因子谱与先前鼻窦手术次数增加有关。因此，3 型炎症标志物可能表明存在一种特别难以治疗的、难治性 CRS 内型。
