Expression and predictive value of type Ⅱ inflammatory cytokines in nasal secretion in eosinophilic chronic rhinosinusitis with nasal polyps
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摘要: 目的 分析嗜酸粒细胞型慢性鼻窦炎伴鼻息肉(ECRSwNP)患者的鼻腔分泌物中Ⅱ型炎症相关细胞因子表达，初步探讨鼻分泌物Ⅱ型炎症细胞因子在预测ECRSwNP中的价值。方法 前瞻性分析2020年11月-2021年6月就诊于北京大学第三医院耳鼻咽喉头颈外科并行内镜鼻窦手术治疗的CRSwNP患者91例，患者均于术前采集SNOT-22评分、Lund-Mackay评分、血嗜酸粒细胞百分比和绝对值；术前留取患者鼻腔分泌物，利用酶联免疫吸附试验检测鼻分泌物Ⅱ型炎症细胞因子(IL-4、IL-5、IL-13、IL-25、IL-33、Eotaxin-3、骨膜蛋白)，术中取鼻息肉组织进行嗜酸粒细胞计数。根据组织中嗜酸粒细胞占比≥10%分为ECRSwNP组和nECRSwNP组，两组之间进行临床基线资料及Ⅱ型炎症细胞因子比较，运用单因素logistic回归分析评估ECRSwNP的相关因素。采用受试者工作特征(ROC)曲线评价各项临床指标的预测潜力。结果 ECRSwNP组的SNOT-22评分、Lund-Mackay评分、血嗜酸粒细胞百分比和绝对值高于nECRSwNP组(P< 0.05)，ECRSwNP组中Ⅱ型黏液炎症因子IL-5和Eotaxin-3的表达显著高于nECRSwNP组(P< 0.01)。logistic回归分析发现，IL-5、Eotaxin-3和血嗜酸粒细胞百分比是ECRSwNP的危险因素(P< 0.05)。ROC分析发现IL-5、Eotaxin-3和血嗜酸粒细胞百分比具有预测诊断价值(P< 0.01)，其中血嗜酸粒细胞百分比预测价值最大(AUC=0.756)；进一步研究发现，由IL-5、Eotaxin-3、SNOT-22评分、鼻窦CT Lund-Mackay评分、血嗜酸粒细胞百分比和绝对值组成的预测模型对ECRSwNP预测效果最优(AUC=0.873)。结论 鼻分泌物Ⅱ型炎症细胞因子IL-5和Eotaxin-3可作为早期诊断ECRSwNP的生物标志物。Abstract: Objective To analyze the expression of type Ⅱ inflammatory-related cytokines in nasal secretions of patients with eosinophilic chronic rhinosinusitis with nasal polyps(ECRSwNP), and to preliminarily explore the role of type Ⅱ inflammatory cytokines in nasal secretions in predicting ECRSwNP.Methods A prospective analysis was made of 91 patients with CRSwNP who underwent endoscopic sinus surgery in Peking University Third Hospital from November 2020 to June 2021. All the selected patients had their SNOT-22 score, Lund-Mackay score and blood eosinophilia collected before surgery. Percentage and absolute value; the nasal secretions of patients were collected before operation, and enzyme-linked immunosorbent assay was used to detect the typeⅡinflammatory cytokines(IL-4, IL-5, IL-13, IL-25, IL-33, Eotaxin-3, periostin), intraoperative nasal polyp tissue was collected for eosinophil count. According to the proportion of eosinophils in the tissue≥10%, they were divided into ECRSwNP group and nECRSwNP group. The clinical baseline data and type Ⅱ inflammatory cytokines were compared between the two groups, and the related factors of ECRSwNP were evaluated by univariate logistic regression analysis. The receiver operating characteristic(ROC) curve was used to evaluate the predictive potential of each clinical index.Results The SNOT-22 score, Lund-Mackay score, blood eosinophil percentage and absolute value in the ECRSwNP group were higher than those in the nECRSwNP group(P< 0.05). In the nECRSwNP group(P< 0.01). Logistic regression analysis found that IL-5, Eotaxin-3 and blood eosinophil percentage were risk factors for ECRSwNP(P< 0.05). ROC analysis found that IL-5, Eotaxin-3 and blood eosinophil percentage had predictive diagnostic value(P< 0.01), among which blood eosinophil percentage had the greatest predictive value(AUC=0.756). The prediction model composed of Eotaxin-3, SNOT-22 score, sinus CT Lund-Mackay score, blood eosinophil percentage and blood eosinophil absolute value had better prediction effect on ECRSwNP(AUC=0.873).Conclusion Type Ⅱ inflammatory cytokines IL-5 and Eotaxin-3 in nasal secretions may be involved as biomarkers for early diagnosis of ECRSwNP.
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Key words:
- sinusitis /
- nasal polyps /
- eosinophils /
- inflammatory cytokines /
- nasal secretions
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表 1 ECRSwNP组和nECRSwNP组患者基本情况和临床特征比较(n=91)
X±S，例(%) 组别 例数 男/女 年龄/岁 哮喘 伴阿司匹林不耐受 伴AR 吸烟史 前次手术史 病程/年 ECRSwNP组 48 38/10 43.96±12.55 8(16.7) 1(2.1) 30(62.5) 13(27.1) 6(12.5) 5.34±6.54 nECRSwNP组 43 28/15 46.72±14.22 3(7.0) 1(2.3) 15(34.9) 8(18.6) 6(14.0) 4.23±5.23 P值 0.134 0.328 0.157 0.937 0.009 0.338 0.838 0.378 
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表 2 鼻分泌物Ⅱ型炎症细胞因子在ECRSwNP和nECRSwNP患者中的比较(n=91)
X±S 项目 ECRSwNP组 nECRSwNP组 P值 IL-4 6.74±1.33 6.36±1.26 0.162 IL-5 10.36±1.57 9.18±1.82 0.001 IL-13 573.58±87.64 569.26±93.05 0.820 IL-25 5.86±1.51 6.00±1.52 0.670 IL-33 49.55±10.79 48.29±12.24 0.604 Eotaxin-3 9.07±1.97 7.95±1.72 0.005 骨膜蛋白 28.45±9.38 28.66±9.79 0.919
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表 3 ECRSwNP患者的单因素logistic回归分析
预测指标 OR 95%CI P值 il-5 1.705 1.180~2.463 0.004 Eotaxin-3 1.871 1.276~2.745 0.001 SNOT-22评分 1.033 0.999~1.069 0.054 鼻窦CT Lund-Mackay评分 1.086 0.996~1.186 0.063 血嗜酸粒细胞百分比 1.383 1.040~1.840 0.026 血嗜酸粒细胞绝对值 2.755 0.261~20.016 0.399
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表 4 ECRSwNP预测因素ROC曲线分析
预测指标 AUC 95%CI值 P值 IL-5 0.695 0.586~0.803 0.001 Eotaxin-3 0.666 0.554~0.778 0.006 SNOT-22评分 0.660 0.549~0.771 0.009 鼻窦CT Lund-Mackay评分 0.644 0.532~0.757 0.010 血嗜酸粒细胞百分比 0.756 0.655~0.856 < 0.001 血嗜酸粒细胞绝对值 0.753 0.654~0.851 < 0.001 预测模型1 0.873 0.802~0.943 < 0.001 预测模型2 0.793 0.700~0.886 < 0.001
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表 5 ECRSwNP预测指标的最佳截断值、敏感度和特异度
预测指标 最佳截断值 敏感度 特异度 IL-5 9.252 0.750 0.581 Eotaxin-3 8.095 0.708 0.605 SNOT-22评分 18.5 0.938 0.302 鼻窦CT Lund-Mackay评分 19.5 0.396 0.814 血嗜酸粒细胞百分比 3.950 0.688 0.744 血嗜酸粒细胞绝对值 0.275 0.604 0.767
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