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摘要: 目的 探索鼻分泌物中可以辅助诊断变应性鼻炎(AR)以及可用于临床治疗效果评估参考的客观标志物。 方法 纳入33例AR患者(AR组)和21例健康对照者(健康对照组)。收集健康对照及AR患者治疗前后的鼻分泌物，检测鼻细胞学、细胞因子(IL-5、IL-6、IL-8、IL-33、IFN-γ)和炎症因子(ECP、MPO)的浓度，比较健康对照及AR患者治疗前后各指标的差异。分析各指标/各指标差值/各指标差值百分比与临床症状评分/评分差值/评分差值百分比的相关性。 结果 与健康对照组比较，AR组治疗前鼻分泌中的ECP、IL-5、IL-6、IL-8、IL-33和IFN-γ均升高(P < 0.05)，MPO未见明显差异；治疗后，AR患者鼻分泌物中的ECP显著下降(P < 0.01)，炎症细胞等级及嗜酸粒细胞百分比下降(P < 0.01)，但MPO、IL-5、IL-6、IL-8、IL-33和IFN-γ均未见明显改变。治疗前后ECP差值与VAS差值具有相关性(r = 0.348，P = 0.047)；IL-5差值与VAS差值(r = 0.406，P = 0.019)和流涕差值(r = 0.429，P = 0.013)具有相关性；鼻分泌物嗜酸粒细胞百分比差值与鼻塞差值具有相关性(r = 0.383，P = 0.028)；嗜酸粒细胞百分比与分级乘积差值与VAS评分(r = 0.417，P = 0.016)和鼻塞差值(r = 0.519，P = 0.002)具有相关性；IFN-γ差值百分比与VAS评分/流涕/喷嚏/鼻部总评分差值百分比具有相关性。 结论 鼻分泌物中ECP、IL-6、IL-8、IL-33因子有望成为辅助诊断AR的客观指标，其中ECP、IL-5、IFN-γ、嗜酸粒细胞百分比与分级乘积有望成为判断患者治疗后症状改善的客观指标。Abstract: Objective This study aimed to explore the biomarkers in nasal secretion that can assist in the diagnosis of allergic rhinitis(AR) and can be used to evaluate the therapeutic effect of AR. Methods Thirty-three patients with AR and 21 healthy controls were included. The nasal secretion of healthy controls and patients with AR(before and after treatment) were collected. The cytology, the concentrations of cytokines(IL-5, IL-6, IL-8, IL-33, IFN-γ) and inflammatory mediators(ECP, MPO) were detected. Then, we compared the differences of various biomarkers between healthy controls and AR patients(before and after treatment group). And analyzed the correlation between each biomarkers/biomarkers difference value/the percentage of biomarkers difference value and clinical symptom score/ score difference value / the percentage of score difference value. Results Compared with normal controls, the levels of ECP, IL-5, IL-6, IL-8, IL-33 and IFN-γ in nasal secretion of AR patients were significantly higher than those of normal controls(P < 0.05). There was no significant difference in MPO. After treatment, ECP decreased significantly(P < 0.01), inflammatory cell grade and eosinophil percentage are also decreased(P < 0.01). However, MPO, IL-5, IL-6, IL-8, IL-33 and IFN-γ did not change significantly. The difference value of ECP before and after treatment was correlated with the difference value of VAS score(r = 0.348, P = 0.047). The difference value of IL-5 was correlated with the difference value of VAS score and rhinorrhea, the correlation coefficients were 0.406(P = 0.019) and 0.429(P = 0.013), respectively. The difference value of eosinophil percentage in nasal secretion before and after treatment was correlated with nasal congestion, and the correlation coefficient was 0.383. The difference value of eosinophil percentage multiplied by inflammatory cell grade before and after treatment was correlated with VAS score(r = 0.417, P = 0.016) and nasal congestion difference value(r = 0.519, P = 0.002). The percentage of difference value of IFN-γ before and after treatment was correlated with the percentage of difference value of VAS score / rhinorrhea / sneeze / total nasal symptom score. Conclusion ECP, IL-6, IL-8 and IL-33 in nasal secretion are expected to be objective biomarkers for auxiliary diagnosis of AR. And ECP, IL-5, IFN-γ, eosinophil percentage multiplied by grade is expected to be an objective index to judge the improvement of patients' symptoms after treatment.
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Key words:
- rhinitis, allergic /
- cytokines /
- inflammatory mediators
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图 1 健康对照组和AR组治疗前后鼻分泌物ECP(1a)、MPO(1b)、IL-5(1c)、IL-6(1d)、IL-8(1e)、IL-33(1f)、IFN-γ(1g)浓度值
表 1 AR组治疗前后VAS和鼻部症状评分
症状评分 AR组治疗前 AR组治疗后 P VAS 69.70±16.60 21.21±16.61 < 0.0001 鼻塞 1.94±0.85 0.55±0.66 < 0.0001 鼻痒 1.48±0.74 0.33±0.53 < 0.0001 喷嚏 1.70±0.80 0.55±0.61 < 0.0001 流涕 1.79±0.59 0.48±0.56 < 0.0001 TNSS 6.91±2.02 1.92±1.54 < 0.0001 
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表 2 AR患者治疗前各因子与各症状评分相关性分析
因子 VAS 鼻塞 鼻痒 流涕 喷嚏 TNSS ECP 0.027 -0.089 0.082 -0.329 -0.334 -0.312 MPO 0.131 0.222 -0.054 -0.024 -0.202 -0.077 IL-5 0.240 0.236 0.034 0.236 0.103 0.249 IL-6 -0.076 -0.054 -0.275 -0.148 -0.170 -0.208 IL-8 -0.289 -0.140 -0.037 -0.304 -0.025 -0.201 IL-33 -0.032 -0.050 -0.145 0.110 -0.110 -0.040 IFN-γ -0.101 -0.186 0.167 0.030 0.064 0.058 EOS% 0.059 0.3601) 0.203 -0.004 0.058 0.276 1)P < 0.05。
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表 3 AR患者治疗前后各因子变化差值与各症状评分变化差值相关性分析
各因子差值 VAS差值 鼻塞差值 鼻痒差值 流涕差值 喷嚏差值 TNSS差值 ECP差值 0.3481) 0.213 0.064 -0.011 -0.141 0.053 MPO差值 0.291 0.030 0.040 -0.053 -0.100 -0.035 IL-5差值 0.4061) 0.055 0.257 0.4291) 0.183 0.322 IL-6差值 0.128 0.007 -0.041 0.254 0.105 0.125 IL-8差值 -0.070 -0.109 -0.261 -0.112 -0.091 -0.124 IL-33差值 0.009 0.002 0.101 0.287 0.108 0.194 IFN-γ差值 0.179 -0.114 -0.013 0.254 0.150 0.143 EOS%差值 0.312 0.3831) 0.050 0.276 0.270 0.354 EOS%×等级差值 0.4171) 0.5192) 0.097 0.043 0.056 0.224 1)P < 0.05，2)P < 0.01。
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表 4 AR患者治疗前后各因子变化百分比与各症状评分变化差值百分比之间相关性分析
各因子差值百分比 VAS差值百分比 鼻塞差值百分比 鼻痒差值百分比 流涕差值百分比 喷嚏差值百分比 TNSS差值百分比 ECP差值百分比 0.334 0.328 -0.176 0.205 -0.067 0.141 MPO差值百分比 -0.034 -0.021 -0.118 -0.135 -0.226 -0.233 IL-5差值百分比 0.255 -0.017 0.264 0.258 0.109 0.232 IL-6差值百分比 -0.141 -0.033 -0.056 0.159 -0.060 -0.025 IL-8差值百分比 0.238 0.288 -0.069 0.111 0.015 0.146 IL-33差值百分比 -0.152 -0.062 0.294 0.123 0.038 0.111 IFN-γ差值百分比 0.4552) 0.217 0.21 0.5072) 0.4021) 0.5162) EOS%差值百分比 0.272 0.111 -0.006 0.226 0.201 0.216 EOS%×等级差值百分比 0.293 0.121 -0.019 0.231 0.238 0.230 1)P < 0.05，2)P < 0.01。
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