支气管哮喘患儿诱导痰中炎性细胞类型及炎症相关细胞因子的临床价值研究

doi:10.3969/j.issn.1673-8640.2021.01.014

摘要/Abstract

摘要：

目的探讨支气管哮喘患儿诱导痰中炎性细胞类型及炎症相关细胞因子的临床价值。方法选取支气管哮喘患儿54例（研究组）作为研究对象,根据哮喘发作期严重程度将研究组分为轻度哮喘组、中度哮喘组和重度哮喘组。另选取性别和年龄相当的支气管肺炎（不合并哮喘）患儿42例作为对照组,检测对照组和研究组治疗前、后诱导痰中炎性细胞类型、T淋巴细胞免疫球蛋白黏蛋白-3（Tim-3）mRNA,以及白细胞介素（IL）-2、IL-4、IL-10、IL-13、干扰素-γ（IFN-γ）等炎症相关细胞因子水平,分析诱导痰中炎症细胞类型以及炎症相关细胞因子在儿童支气管哮喘临床诊断中的价值。结果治疗前,研究组诱导痰中嗜酸性粒细胞百分比、淋巴细胞百分比、Tim-3 mRNA、IL-4、IL-13、IFN-γ及IFN-γ/IL-10水平均高于对照组,差异有统计学意义（P<0.05）;IL-2、IL-10及辅助性T细胞（Th）1/Th2水平均低于对照组,差异有统计学意义（P<0.05）。中度哮喘组和重度哮喘组患儿嗜酸性粒细胞百分比、中性粒细胞百分比、淋巴细胞百分比、Tim-3 mRNA、IL-4、IL-13、IFN-γ及IFN-γ/IL-10水平高于轻度哮喘组、对照组患儿,差异有统计学意义（P<0.05）;IL-2、IL-10及Th1/Th2低于轻度哮喘组、对照组患儿,差异有统计学意义（P<0.05）。Logistic回归分析结果显示,嗜酸性粒细胞比例、Tim-3 mRNA、IFN-γ、IL-10、IFN-γ/IL-10及Th1/Th2为儿童支气管哮喘的独立影响因素。受试者工作特征（ROC）曲线分析结果显示,嗜酸性粒细胞百分比、Tim-3 mRNA、IFN-γ、IFN-γ/IL-10及Th1/Th2对儿童支气管哮喘及支气管肺炎（不合并哮喘）具有一定的鉴别作用。结论支气管哮喘患儿诱导痰中嗜酸性粒细胞百分比、Tim-3 mRNA、IFN-γ、IFN-γ/IL-10及Th1/Th2的表达异常有助于疾病的病情监测、疗效评估以及与儿童支气管肺炎（不合并哮喘）的鉴别诊断。

关键词: 支气管哮喘, 诱导痰, 炎症相关细胞因子, 儿童

Abstract:

Objective To explore the clinical value of inflammatory cell types and inflammatory cytokines in induced sputum in children with bronchial asthma. Methods Fifty-four children with bronchial asthma were selected as the research objects（study group）,and subdivided into mild asthma group,moderate asthma group,and severe asthma group. Forty-two sex- and age-matched children with bronchopneumonia（without asthma）were selected into control group. The inflammatory cell types,T cell immunoglobulin and mucin-3 （Tim-3） mRNA,and inflammation-related cytokines [interleukin（IL）-2,IL-4,IL-10,IL-13,interferon gamma（IFN-γ）] in induced sputum were detected before and after treatment. Results Before treatment,in the induced sputum,eosinophilratio,lymphocyte ratio,Tim-3 mRNA,IL-4,IL-13,IFN-γ and IFN-γ/IL-10 in the study group were significantly higher than those in the control group（P<0.05）,while the levels of IL-2,IL-10 and Th1/Th2 in the study group were significantly lower than those in the control group（P<0.05）. Children with moderate and severe asthma had higher levels of the percentage of eosinophil,the percentage of neutrophil,the percentage of lymphocyte,Tim-3 mRNA,IL-4,IL-13,IFN-γ and IFN-γ/IL-10 than children with mild asthma and children with bronchopneumonia（P<0.05）,while IL-2,IL-10 and Th1/Th2 in the children with moderate and severe asthma were significantly lower than those in the children with mild asthma and children with bronchopneumonia（P<0.05）. Logistic regression analysis showed that the proportion of eosinophils,Tim-3 mRNA,IFN-γ,IL-10,IFN-γ/IL-10 and Th1/Th2 were independent influencing factors of bronchial asthma in children. Receiver operating characteristic （ROC） curve analysis showed that the percentage of eosinophils,Tim-3 mRNA,IFN-γ,IFN-γ/IL-10 and Th1/Th2 had a certain differential effect on bronchial asthma and bronchial pneumonia in children. Conclusion Abnormal expression of eosinophils,Tim-3 mRNA,IFN-γ,IFN-γ/IL-10 and Th1/Th2 in induced sputum of children with bronchial asthma can help to monitor the disease condition,evaluate the efficacy and discriminatebronchopneumonia in children without asthma.

Key words: Bronchial asthma, Inducedsputum, Inflammatory cytokines, Children

中图分类号:

R446.1

高伟霞, 秦小菀, 刘阳, 张靖, 丁显春. 支气管哮喘患儿诱导痰中炎性细胞类型及炎症相关细胞因子的临床价值研究[J]. 检验医学, 2021, 36(1): 69-74.

GAO Weixia, QIN Xiaowan, LIU Yang, ZHANG Jing, DING Xianchun. Clinical significance of inflammatory cell types and inflammatory cytokines in sputum induced by bronchial asthma in children[J]. Laboratory Medicine, 2021, 36(1): 69-74.

图/表 4

参考文献 19

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组别	嗜酸性粒细胞百分比/%	中性粒细胞百分比/%	单核细胞百分比/%	淋巴细胞百分比/%	Tim-3 mRNA	IL-4/（pg/mL）
对照组	8.86±1.39	50.85±8.22	25.94±9.42	10.94±6.35	0.28±0.11	31.96±5.77
研究组	19.22±5.16^*	52.92±13.85	24.45±12.55	19.48±3.94^*	0.63±0.09^*	41.33±9.05^*
轻度哮喘组	10.32±2.61^*	41.63±7.03	34.03±8.44	11.45±2.36	0.34±0.11	23.01±5.02
中度哮喘组	18.64±3.22^*#	67.32±10.28^*#	35.83±6.97	18.42±1.84^*#	0.59±0.07^*#	38.44±5.16^*#
重度哮喘组	24.98±3.24^*#△	72.35±4.00^*#	39.21±2.14	22.38±1.82^*#	0.72±0.10^*#△	42.56±7.65^*#
组别	IL-13/（ng/mL）	IL-2/（pg/mL）	IL-10/（ng/mL）	IFN-γ/（pg/mL）	IFN-γ/IL-10	Th1/Th2
对照组	114.31±18.94	190.94±21.90	221.35±54.88	32.41±8.29	0.15±0.05	6.78±1.09
研究组	140.28±31.85^*	139.12±24.82^*	170.64±41.20^*	49.54±14.63^*	0.31±0.09^*	3.74±0.83^*
轻度哮喘组	99.85±13.94	189.43±16.43	220.81±21.39	39.69±7.08	0.17±0.08	4.58±0.45^*
中度哮喘组	122.85±20.45	140.06±16.53^*#	165.34±20.38^*#	44.87±7.92^*#	0.25±0.11^*#	3.62±0.51^*#
重度哮喘组	148.62±19.35^*#	118.63±17.44^*#	152.97±19.57^*#	51.82±9.15^*#	0.33±0.08^*#△	3.01±0.43^*#△

组别	嗜酸性粒细胞百分比/%	中性粒细胞百分比/%	单核细胞百分比/%	淋巴细胞百分比/%	Tim-3 mRNA	IL-4/（pg/mL）
对照组	8.86±1.39	50.85±8.22	25.94±9.42	10.94±6.35	0.28±0.11	31.96±5.77
研究组	19.22±5.16^*	52.92±13.85	24.45±12.55	19.48±3.94^*	0.63±0.09^*	41.33±9.05^*
轻度哮喘组	10.32±2.61^*	41.63±7.03	34.03±8.44	11.45±2.36	0.34±0.11	23.01±5.02
中度哮喘组	18.64±3.22^*#	67.32±10.28^*#	35.83±6.97	18.42±1.84^*#	0.59±0.07^*#	38.44±5.16^*#
重度哮喘组	24.98±3.24^*#△	72.35±4.00^*#	39.21±2.14	22.38±1.82^*#	0.72±0.10^*#△	42.56±7.65^*#
组别	IL-13/（ng/mL）	IL-2/（pg/mL）	IL-10/（ng/mL）	IFN-γ/（pg/mL）	IFN-γ/IL-10	Th1/Th2
对照组	114.31±18.94	190.94±21.90	221.35±54.88	32.41±8.29	0.15±0.05	6.78±1.09
研究组	140.28±31.85^*	139.12±24.82^*	170.64±41.20^*	49.54±14.63^*	0.31±0.09^*	3.74±0.83^*
轻度哮喘组	99.85±13.94	189.43±16.43	220.81±21.39	39.69±7.08	0.17±0.08	4.58±0.45^*
中度哮喘组	122.85±20.45	140.06±16.53^*#	165.34±20.38^*#	44.87±7.92^*#	0.25±0.11^*#	3.62±0.51^*#
重度哮喘组	148.62±19.35^*#	118.63±17.44^*#	152.97±19.57^*#	51.82±9.15^*#	0.33±0.08^*#△	3.01±0.43^*#△

组别	例数	嗜酸性粒细胞百分比/%	中性粒细胞百分比/%	单核细胞百分比/%	淋巴细胞百分比/%	Tim-3 mRNA	IL-2/（pg/mL）
无效组	6
治疗前		19.69±4.74	50.55±7.04	23.99±13.11	18.03±4.44	0.70±0.10	141.39±30.55
治疗后		16.29±5.44^#	53.25±10.06	22.83±11.26	13.85±4.13^#	0.62±0.09	179.33±49.20^#
有效组	48
治疗前		19.01±5.92	51.86±7.96	24.02±12.26	19.48±3.94	0.73±0.09	139.03±29.94
治疗后		8.02±3.79^*#	53.83±9.26	22.30±10.68	12.39±4.13^#	0.42±0.11^*#	180.63±39.97^#
组别	IL-4/（pg/mL）		IL-10/（ng/L^）	IL-13/（ng/L）	IFN-γ/（pg/mL）	IFN-γ/IL-10	Th1/Th2
无效组
治疗前	40.94±10.11		168.54±53.82	139.15±33.78	49.33±15.98	0.32±0.09	3.62±0.96
治疗后	36.72±9.02^#		217.88±49.68^#	111.76±30.02^#	39.78±16.35^#	0.20±0.05^#	4.92±1.11^#
有效组
治疗前	41.59±9.76		171.39±51.48	141.75±30.96	50.41±14.63	0.34±0.07	3.80±1.07
治疗后	34.19±9.23^#		214.53±43.37^#	114.04±29.89^#	25.38±15.86^*#	0.12±0.04^*#	5.67±1.22^*#

组别	例数	嗜酸性粒细胞百分比/%	中性粒细胞百分比/%	单核细胞百分比/%	淋巴细胞百分比/%	Tim-3 mRNA	IL-2/（pg/mL）
无效组	6
治疗前		19.69±4.74	50.55±7.04	23.99±13.11	18.03±4.44	0.70±0.10	141.39±30.55
治疗后		16.29±5.44^#	53.25±10.06	22.83±11.26	13.85±4.13^#	0.62±0.09	179.33±49.20^#
有效组	48
治疗前		19.01±5.92	51.86±7.96	24.02±12.26	19.48±3.94	0.73±0.09	139.03±29.94
治疗后		8.02±3.79^*#	53.83±9.26	22.30±10.68	12.39±4.13^#	0.42±0.11^*#	180.63±39.97^#
组别	IL-4/（pg/mL）		IL-10/（ng/L^）	IL-13/（ng/L）	IFN-γ/（pg/mL）	IFN-γ/IL-10	Th1/Th2
无效组
治疗前	40.94±10.11		168.54±53.82	139.15±33.78	49.33±15.98	0.32±0.09	3.62±0.96
治疗后	36.72±9.02^#		217.88±49.68^#	111.76±30.02^#	39.78±16.35^#	0.20±0.05^#	4.92±1.11^#
有效组
治疗前	41.59±9.76		171.39±51.48	141.75±30.96	50.41±14.63	0.34±0.07	3.80±1.07
治疗后	34.19±9.23^#		214.53±43.37^#	114.04±29.89^#	25.38±15.86^*#	0.12±0.04^*#	5.67±1.22^*#

检测指标	敏感性/%	特异性/%	阳性预测值/%	阴性预测值/%	诊断准确率/%	曲线下面积	95%CI
Tim-3 mRNA	73.39	80.51	81.69	77.82	73.15	0.711	0.606~0.822
IFN-γ	74.02	80.93	81.76	78.86	73.92	0.719	0.613~0.825
嗜酸性粒细胞百分比	76.18	82.25	83.60	77.91	76.75	0.737	0.614~0.835
IFN-γ/IL-10	80.32	85.65	87.69	81.25	80.88	0.798	0.701~0.895
Th1/Th2	78.92	83.59	85.97	80.03	79.43	0.784	0.680~0.888