Expression and clinical significance of NLRP3 and TLR4 in peripheral blood of children with acute wheezing caused by human rhinovirus

doi:10.3877/cma.j.issn.1673-5250.2024.04.011

Objective

To evaluate the expression and clinical significance of NOD-like receptor protein 3（NLRP3）and Toll-like receptor 4（TLR4）in the peripheral blood of children with acute wheezing caused by human rhinovirus（HRV）infection.

Methods

From September 2023 to March 2024，a total of 126 children aged 3-8 who were admitted to Department of Emergency，Qingdao Women and Children's Hospital for the first time with acute wheezing due to HRV infection were selected into this study.According to the severity of the disease，they were divided into mild and moderate group （n=80）and severe group （n=46）.The age，weight，body mass index （BMI），white blood count （WBC），neutrophil count （NEUT），lymphocyte count（LY），C reaction protein（CRP），interleukin （IL）-6，TLR4 and NLRP3 m RNA levels of the two groups were compared by independent samples t test.Chi-square test was used to compare the sex composition ratio，percentage of eczema history and parental allergy history between the two groups.Pearson correlation was used to analyze the correlation between IL-6，TLR4 and NLRP3 m RNA and the severity of acute wheezing attack in children.This study follows the ethical principles and was approved by the Hospital Ethics Committee （Approval No.QFELL-KY-2020-23）.

Results

①There were no statistically significant differences in the gender composition ratio，age，weight，BMI，and the percentage of eczema history and parental allergy history between two groups （P ＞0.05）.②The levels of IL-6，TLR4 and NLRP3 m RNA in the mild to moderate group were lower than those in the severe group （P＜0.05）.③The severity of wheezing in patients with acute wheezing caused by HRV was positively correlated with the levels of IL-6，TLR4 and NLRP3 m RNA （r=0.772，0.792，0.897，P＜0.001）.④There was a positive linear correlation between TLR4 and NLRP3 mRNA （r=0.820，P ＜0.001）.

Conclusions

NLRP3 and TLR4 in peripheral blood of children with acute wheezing caused by HRV infection are closely related to the severity of wheezing.NLRP3 may mediate airway hyperresponsiveness in patients with HRV infection by i nducing IL-6 secretion and up-regulating TLR4 expression，and induce acute wheezing attack.

Key words: Human rhinovirus, Wheezing, NOD-like receptor protein 3, Toll-like receptor 4, Child

表1 2组因HRV 感染致首次喘息急性发作患儿一般临床资料比较

组别	例数	性别［例数（%）］		年龄（岁， $\overset{ˉ}{x}$ ±s）	体重（kg， $\overset{ˉ}{x}$ ±s）	BMI（kg/m²， $\overset{ˉ}{x}$ ±s）	湿疹史［例数（%）］	父母变态反应史［例数（%）］
组别	例数	男	女	年龄（岁， $\overset{ˉ}{x}$ ±s）	体重（kg， $\overset{ˉ}{x}$ ±s）	BMI（kg/m²， $\overset{ˉ}{x}$ ±s）	湿疹史［例数（%）］	父母变态反应史［例数（%）］
轻、中度组	80	36（45.0）	44（55.0）	5.1±1.4	16.5±1.9	13.6±1.8	17（21.3）	8（10.0）
重度组	46	22（47.8）	24（52.2）	4.7±0.9	15.6±1.7	14.1±2.6	13（28.3）	5（10.9）
统计量		χ²=0.09		t=1.91	t=-0.07	t=-1.33	t=0.45	χ²=0.17
P值		0.759		0.069	0.948	0.187	0.501	0.678

表1 2组因HRV 感染致首次喘息急性发作患儿一般临床资料比较

组别	例数	性别［例数（%）］		年龄（岁， $\overset{ˉ}{x}$ ±s）	体重（kg， $\overset{ˉ}{x}$ ±s）	BMI（kg/m²， $\overset{ˉ}{x}$ ±s）	湿疹史［例数（%）］	父母变态反应史［例数（%）］
组别	例数	男	女	年龄（岁， $\overset{ˉ}{x}$ ±s）	体重（kg， $\overset{ˉ}{x}$ ±s）	BMI（kg/m²， $\overset{ˉ}{x}$ ±s）	湿疹史［例数（%）］	父母变态反应史［例数（%）］
轻、中度组	80	36（45.0）	44（55.0）	5.1±1.4	16.5±1.9	13.6±1.8	17（21.3）	8（10.0）
重度组	46	22（47.8）	24（52.2）	4.7±0.9	15.6±1.7	14.1±2.6	13（28.3）	5（10.9）
统计量		χ²=0.09		t=1.91	t=-0.07	t=-1.33	t=0.45	χ²=0.17
P值		0.759		0.069	0.948	0.187	0.501	0.678

表2 2组因HRV 感染致首次喘息急性发作患儿实验室检查结果比较（±s）

组别	例数	WBC（×10⁹/L）	NEUT（×10⁹/L）	LY（×10⁹/L）	CRP（mg/L）	IL-6（pg/mL）	TLR4（ng/L）	NLRP3 mRNA
轻、中度组	80	8.2±2.5	5.0±1.6	3.2±1.9	7.3±3.7	166.4±18.4	53.8±4.7	0.4±0.1
重度组	46	7.6±1.6	4.6±1.7	2.9±1.4	6.5±2.8	224.8±22.4	71.6±5.3	1.7±10.3
t值		1.53	1.22	1.07	1.18	-12.85	-16.18	-23.85
P值		0.129	0.225	0.289	0.242	＜0.001	＜0.001	＜0.001

表2 2组因HRV 感染致首次喘息急性发作患儿实验室检查结果比较（±s）

组别	例数	WBC（×10⁹/L）	NEUT（×10⁹/L）	LY（×10⁹/L）	CRP（mg/L）	IL-6（pg/mL）	TLR4（ng/L）	NLRP3 mRNA
轻、中度组	80	8.2±2.5	5.0±1.6	3.2±1.9	7.3±3.7	166.4±18.4	53.8±4.7	0.4±0.1
重度组	46	7.6±1.6	4.6±1.7	2.9±1.4	6.5±2.8	224.8±22.4	71.6±5.3	1.7±10.3
t值		1.53	1.22	1.07	1.18	-12.85	-16.18	-23.85
P值		0.129	0.225	0.289	0.242	＜0.001	＜0.001	＜0.001

图1 NLRP3 m RNA 及IL-6、TLR4与儿童喘息严重程度相关性的热力图注：IL-6 为白细胞介素6，TLR4 为Toll样受体4，NLRP3 为NOD样受体蛋白3。Severity为疾病严重程度，value表示相关性强度

［1］	Li ZJ，Zhang HY，Ren LL，et al.Etiological and epidemiological features of acute respiratory infections in China［J］.Nat Commun，2021，12（1）：5026.DOI：10.1038/s41467-021-25120-6.
［2］	万以秋，蔡茹，姜法春，等.青岛2020年冬季上呼吸道感染患者中人鼻病毒的分子流行病学特征［J］.中华微生物学和免疫学杂志，2022，42（4）：310-316.DOI：10.3760/cma.j.cn112309-20211231-00440.Wan YQ，Cai G，Jiang FC，et al.Molecular epidemiological characteristics of human rhinovirus in patients with upper respiratory tract infection in Qingdao in the winter of 2020［J］.Chin J Microbiol Immunol，2022，42（4）：310-316.DOI：10.3760/cma.j.cn112309-20211231-00440.
［3］	Feddema JJ，Claassen E.Prevalence of viral respiratory infections amongst asthmatics：results of a Meta-regression analysis［J］.Respir Med，2020，173：106020.DOI：10.1016/j.rmed.2020.106020.
［4］	Su YT，Lin YT，Yang CC，et al.High correlation between human rhinovirus type C and children with asthma exacerbations in Taiwan［J］.J Microbiol Immunol Infect，2020，53（4）：561-568.DOI：10.1016/j.jmii.2018.12.001.
［5］	王擎，罗明，王雪，等.人鼻病毒的研究进展［J］.中华实验和临床病毒学杂志，2023，37（2）：216-221.DOI：10.3760/cma.j.cn112866-20220928-00200.Wang Q，Luo M，Wang X，et al.Advances in research on human rhinovirus ［J］.Chin J Experimental Clin Virol，2023，37（2）：216-221.DOI：10.3760/cma.j.cn112866-20220928-00200.
［6］	Turunen R，Vuorinen T，Bochkov Y，et al.Clinical and virus surveillance after the first wheezing episode：special reference to rhinovirus A and C species［J］.Pediatr Infect Dis J，2017，36（6）：539-544.DOI：10.1097/INF.0000000 000001495.
［7］	Tran DN，Trinh QD，Pham NT，et al.Human rhinovirus infections in hospitalized children：clinical，epidemiological and virological features［J］.Epidemiol Infect，2016，144（2）：346-354.DOI：10.1017/S0950268815000953.
［8］	Miller EK，Khuri-Bulos N，Williams JV，et al.Human rhinovirus C associated with wheezing in hospitalised children in the Middle East［J］.J Clin Virol，2009，46（1）：85-89.DOI：10.1016/j.jcv.2009.06.007.
［9］	王燕.儿童哮喘急性发作与人鼻病毒相关基因的生物信息学分析［J］.妇儿健康导刊，2023，2（24）：7-10，19.Wang Y.Bioinformatics analysis of acute exacerbation of pediatric asthma and human rhinovirus related genes［J］.J Women Children Health Guide，2023，2（24）：7-10，19.
［10］	惠超，刘馨.NOD样受体热蛋白结构域相关蛋白3对哮喘小鼠气道炎症反应及细胞焦亡的调控作用［J］.中国当代儿科杂志，2021，23（9）：959-964.DOI：10.7499/j.issn.1008-8830.2106107.Hui C，Liu X.Regulatory effect of NLRP3 on airway inflammatory response and pyroptosis in mice with asthma［J］.Chin J Contemp Pediatr，2021，23（9）：959-964.DOI：10.7499/j.issn.1008-8830.2106107.
［11］	葛瑜，李建木，冯玲玲，等.布地奈德联合重组人干扰素α-1b治疗急性婴幼儿毛细支气管炎的临床疗效［J/OL］.中华妇幼临床医学杂志（电子版），2021，17（3）：298-304.DOI：10.3877/cma.j.issn.1673-5250.2021.03.010.Ge Y，Li JM，Feng LL，et al.Clinical efficacy of budesonide combined with recombinant human interferonα-1b in the treatment of acute infantile bronchiolitis［J/OL］.Chin J Obstet Gynecol Pediatr （Electron Ed），2021，17（3）：298-304.DOI：10.3877/cma.j.issn.1673-5250.2021.03.010.
［12］	娄丽丽，刘瀚旻.儿童哮喘易感基因及表观遗传学研究现状［J/OL］.中华妇幼临床医学杂志（电子版），2023，19（3）：249-255.DOI：10.3877/cma.j.issn.1673-5250.2023.03.001.Lou LL，Liu HM.Current research status of susceptibility genes and epigenetics on childhood asthma［J/OL］.Chin J Obstet Gynecol Pediatr （Electron Ed），2023，19（3）：249-255.DOI：10.3877/cma.j.issn.1673-5250.2023.03.001.
［13］	中华医学会儿科学分会呼吸学组，《中华儿科杂志》编辑委员会.儿童支气管哮喘诊断与防治指南（2016年版）［J］.中华儿科杂志，2016，54（3）：167-181.DOI：10.3760/cma.j.issn.0578-1310.2016.03.003.The Subspecialty Group of Respiratory Diseases，The Society of Pediatrics，Chinese Medical Association；The Editorial Board，Chinese Journal ofPediatrics.Guideline for the diagnosis and optimal management of asthma in children（2016）［J］.Chin J Pediatr，2016，54（3）：167-181.DOI：10.3760/cma.j.issn.0578-1310.2016.03.003.
［14］	Vandini S，Biagi C，Fischer M，et al.Impact of rhinovirus infections in children［J］.Viruses，2019，11（6）：521.DOI：10.3390/v11060521.
［15］	Jartti T，Smits HH，Bønnelykke K，et al.Bronchiolitis needs a revisit：distinguishing between virus entities and their treatments［J］.Allergy，2019，74（1）：40-52.DOI：10.1111/all.13624.
［16］	Dumas O，Hasegawa K，Mansbach JM，et al.Severe bronchiolitis profiles and risk of recurrent wheeze by age 3 years［J］.J Allergy Clin Immunol，2019，143（4）：1371-1379.e7.DOI：10.1016/j.jaci.2018.08.043.
［17］	Kan OK，Washio Y，Oki T，et al.Effects of treatment with corticosteroids on human rhinovirus-induced asthma exacerbations in pediatric inpatients：a prospective observational study［J］.BMC Pulm Med，2023，23（1）：487.DOI：10.1186/s12890-023-02798-6.
［18］	Hasegawa K，Mansbach JM，Bochkov YA，et al.Association of rhinovirus C bronchiolitis and immunoglobulin e sensitization during infancy with development of recurrent wheeze［J］.JAMA Pediatr，2019，173（6）：544-552.DOI：10.1001/jamapediatrics.2019.0384.
［19］	Bønnelykke K，Coleman AT，Evans MD，et al.Cadherinrelated family member 3 genetics and rhinovirus C respiratory illnesses［J］.Am J Respir Crit Care Med，2018，197（5）：589-594.DOI：10.1164/rccm.201705-1021OC.
［20］	Jamieson KC，Warner SM，Leigh R，et al.Rhinovirus in the pathogenesis and clinical course of asthma［J］.Chest，2015，148（6）：1508-1516.DOI：10.1378/chest.15-1335.
［21］	Blaas D，Fuchs R.Mechanism of human rhinovirus infections［J］.Mol Cell Pediatr，2016，3（1）：21.DOI：10.1186/s40348-016-0049-3.
［22］	Xu W，Wang Y，Ma Y，et al.MiR-223 plays a protecting role in neutrophilic asthmatic mice through the inhibition of NLRP3 inflammasome［J］.Respir Res，2020，21（1）：116.DOI：10.1186/s12931-020-01374-4.
［23］	Chen X，Wang K，Yao Q，et al.The relationship b etween the rs4986791 variant of the TLR4 gene and the severity of bronchial asthma in children［J］.Asian Pac J Allergy Immunol，2024，42（2）：159-164.DOI：10.12932/AP-100920-0954.
［24］	Qiu Q，Yang Z，Cao F，et al.Activation of NLRP3 inflammasome by lymphocytic microparticles via TLR4 pathway contributes to airway inflammation［J］.Exp Cell Res，2020，386（2）：111737.DOI：10.1016/j.yexcr.2019.111737.

[1]	Yuxiao Zhang, Fan Yang, Meng Mao. Interpretation of Catch-Up Growth in Infants and Young Children with Faltering Growth：Expert Opinion to Guide General Clinicians[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2024, 20(04): 361-366.
[2]	Yanan Wang, Dan Liu, Zhengnong Cao, Huimin Jia. Clinical diagnosis and treatment of children with late-onset congenital diaphragmatic hernia[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2024, 20(04): 410-419.
[3]	Guihua Chen, Xiaoling Zhong, Yu Xie, Hui Wang, Jiang Xie, Taoyi Yang. Clinical analysis of the timeliness of vaccination in children with special health care needs complicated with liver disease[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2024, 20(04): 431-439.
[4]	Mengsi Zhang, Yiqun Ma, Lijuan Meng, Hui Zhu, Jinfeng Fu. Observation on the effect of the combined use of pressure gloves, webbed finger compression straps and foam silicone gel sheeting after surgery in children with cicatricial syndactyly[J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2024, 19(04): 329-334.
[5]	Baoying Zheng, Xiaolan Huang, Nan Jia, Chunmei Zhu. Early warning indicators of children with refractory mycoplasma pneumoniae pneumonia[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2024, 18(04): 215-221.
[6]	Xiaoli Yang, Wanfu Li, Zhu Ma, Lan Ma, Yi Zheng, Xiaoli Fu, Jing Wang. Application effect of one-step forceps needle method in laparoscopic high ligation of hernia sac in children[J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2024, 18(05): 535-538.
[7]	Weijun Zheng, Yifan Fang, Dianming Wu, Xiang Wang, Fei Chen, Mingkun Liu. Diagnosis and treatment of congenital malrotation of the intestine: a summary of 10 years of experience in a single center[J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2024, 18(03): 338-341.
[8]	Hebei Ding, Xun Wang, Weiguo Chen. Comparison of application of sevoflurane inhalation anesthesia and propofol intravenous anesthesia in pediatric indirect inguinal hernia surgery[J]. Chinese Journal of Hernia and Abdominal Wall Surgery(Electronic Edition), 2024, 18(05): 570-574.
[9]	Pan Li, Dengfei Wei, Kekun Qiao, Xionggang Li. Comparison of ultrasound-guided sacral canal block with ilioinguinal and iliohypogastric nerve block for pediatric laparoscopic high ligation of hernial sac[J]. Chinese Journal of Hernia and Abdominal Wall Surgery(Electronic Edition), 2024, 18(03): 326-330.
[10]	Jixiao Zeng, Xiaogang Xu, Xinxing Wang, Fei Liu, Menglong Lan, Boyuan Tao, Zijian Liang, Zhihua Ye, Yuanyuan Luo. Da Vinci robotic-assisted Swenson-like pull through for Hirschsprung disease[J]. Chinese Journal of Laparoscopic Surgery(Electronic Edition), 2024, 17(04): 239-243.
[11]	Chinese Society of Organ Transplantation of Chinese Medical Association, Surgery Group of Chinese Society of Surgery of Chinese Medical Association, Transplantation Group of Chinese Society of Surgery of Chinese Medical Association, South China Alliance of Split Liver Transplantation. Chinese Clinical Practice Guidelines on Split Liver Transplantation in Children[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2024, 13(05): 593-601.
[12]	Jun Liu, Wenjing Qiu, Fanghao Sun, Songying Li, Shuhong Yi, Binsheng Fu, Yang Yang, Hui Luo. Comparison of in vivo and in vitro split liver transplantation in pediatric liver transplantation[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2024, 13(05): 688-693.
[13]	Jingting Sun, Na Li, Minghui Luo, Yaoyao Gao, Yihang Bai, Guozhen Zhu. Effect and mechanism of short-chain fatty acids on inflammation and fibrosis of mice with renal ischemia-reperfusion injury[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2024, 13(04): 181-187.
[14]	Xiaoyu Wang, Qunying Guo, Yameng Niu, Chengsong Zhao. Practice of promoting equal access to pediatric medical care in public children's hospitals[J]. Chinese Journal of Clinicians(Electronic Edition), 2024, 18(04): 383-387.
[15]	Nuo Yan, Wei Deng, Yingxia Zhang, Danyang He, Ning Fan. Diagnostic value of urinary system ultrasound combined with procalcitonin for high-grade vesicoureteral reflux in children[J]. Chinese Journal of Diagnostics(Electronic Edition), 2024, 12(03): 149-154.

Viewed

Full text

Abstract

Please choose a citation manager

Content to export