Elevated mucus interleukin-17A levels are associated with increased prior sinus surgery for chronic rhinosinusitis
Elevated mucus interleukin-17A levels are associated with increased prior sinus surgery for chronic rhinosinusitis
复制标题
DOI：
10.1002/alr.22652
复制
发表时间：
2020-07-23
影响因子：
6.4
通讯作者：
Chowdhury, Naweed I.
中科院分区：
文献类型：
--
作者：
Chapurin, Nikita;Li, Ping;Chowdhury, Naweed I.
背景分子生物学的最新进展使得识别慢性鼻-鼻窦炎(CRS)的潜在炎症内型成为可能，先前的工作表明基于细胞因子信号的不同短期手术结果轨迹。然而，缺乏评估长期治疗失败和基于炎症生物标记物的翻修手术的数据。方法对231例选择手术治疗的CRS患者的前瞻性横断面资料进行回顾性分析。术中粘液标本用多重流式细胞仪珠法定量采集炎性细胞因子。对细胞因子水平和先前手术次数之间的单变量Spearman相关性进行评估。逐步调整的多变量泊松回归分析被用来模拟患者报告的鼻窦手术前计数作为细胞因子水平的函数。结果多种细胞因子(IL-1β、IL-4、IL-5、IL-6、IL-8、IL-10、IL-13、IL-17A、肿瘤坏死因子α、干扰素γ、嗜酸性粒细胞趋化因子)与既往手术次数呈显著正相关。然而，在调整了年龄(β=0.345，p=0.0003)、伦德-麦凯评分(β=-0.046，p=0.02)、阿司匹林加重呼吸道疾病病史(β=1.01，p<；0.0001)和过敏性真菌性鼻-鼻窦炎(β=1.08，p<；0.0001)的重要协变量后，只有较高的IL-17A水平与较高的鼻腔手术次数(β=0.018，p=0.0036)独立相关。较高水平的活化调节、正常T细胞表达和分泌(RANTES)与较低的手术次数相反(β=-0.17，p=0.048)。结论IL-17A占优势的细胞因子与既往鼻窦手术的增加有关。因此，3型炎症标志物可能提示一种特别难以治疗的顽固性CRS内型。
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]-1 beta, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-17A, tumor necrosis factor alpha [TNF-alpha], interferon gamma [IFN-gamma], 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 (beta = 0.345,p= 0.0003) after adjusting for the significant covariates of age (beta = 0.018,p= 0.0036), Lund-Mackay score (beta = -0.046,p= 0.02), history of aspirin-exacerbated respiratory disease (beta = 1.01,p< 0.0001) and allergic fungal rhinosinusitis (beta = 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 (beta = -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.