Analysis of serum levels of EDN, IL-13, TGF-β1 and risk factors in children with recurrent wheezing of mycoplasma pneumoniae infection

doi:10.11958/20241823

Abstract

Abstract:

Objective To investigate serum levels of eosinophilic neurotoxin (EDN), interleukin (IL)-13 and transforming growth factor (TGF)-β1 in children with recurrent wheezing of mycoplasma pneumoniae (MP) infection and analyze risk factors of recurrent wheezing with MP infection. Methods A total of 80 children with MP infection were divided into the MP infection recurrence wheezing group (45 cases) and the MP infection non-wheezing group (35 cases) according to the previous history of MP infection with wheezing, and 35 children with acute attacks of bronchial asthma were selected as the asthma group. The levels of EDN, IL-13 and TGF-β1 were determined by enzyme-linked immunosorbent assay. Multivariate Logistic regression analysis was performed to analyze risk factors of MP infection recurrence and wheezing. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of EDN, IL-13 and TGF-β1 on MP infection recurrence and wheezing. Results Compared with the non-asthmatic group, levels of EDN, IL-13 and TGF-β1 were higher in the recurrent asthmatic group and the asthmatic group (P<0.05). There were no significant differences in EDN, IL-13 and TGF-β1 levels between the asthma group and the recurrent asthmatic group. Univariate analysis showed that the birth weight was lower in the recurrent wheezing group than that of the non-wheezing group, and the proportion of atopic constitution, the first and second degree relatives allergy history, smoke exposure and hospital stay ≥7 d were higher than those of the non-wheezing group (P<0.05). Multivariate Logistic regression analysis showed that higher levels of EDN, IL-13, TGF-β1, atopic constitution and smoke exposure were risk factors for recurrent wheezing of MP infection (P<0.05). ROC curve results showed that the AUC of EDN, IL-13 and TGF-β1 for predicting the recurrence of MP infection and wheeting was 0.688, 0.662 and 0.689, respectively, and the AUC of the combined prediction of EDN, IL-13 and TGF-β1 was 0.765, which was the most effective than each single index. Conclusion Serum levels of EDN, IL-13 and TGF-β1 increase in children with recurrent wheezing of MP infection, and their serum levels may predict repeated wheezing in children after MP infection, providing guidance for clinical intervention.

Key words: mycoplasma pneumoniae, eosinophil-derived neurotoxin, transforming growth factor beta1, interleukin-13, child, wheezing

CLC Number:

R725.62

Figures/Tables 5

References 23

[1]	KONG K, DING Y, WU B, et al. Clinical predictors of wheezing among children infected with Mycoplasma pneumoniae[J]. Front Pediatr, 2021, 9:693658. doi:10.3389/fped.2021.693658.
[2]	MAKIEIEVA N, MALAKHOVA V, VASYLCHENKO Y, et al. Are level of IL-13 and IL-4 predictive for formation of chronic inflammation in children with asthma?[J]. Adv Respir Med, 2020, 88(4):320-326. doi:10.5603/ARM.a2020.0108.
[3]	CHAKRABORTY S, HAMMAR K S, FILIOU A E, et al. Longitudinal eosinophil-derived neurotoxin measurements and asthma development in preschool wheezers[J]. Clin Exp Allergy, 2022, 52(11):1338-1342. doi:10.1111/cea.14210.
[4]	KIM S, KIM H W, CHANG S H, et al. Bee venom prevents mucin 5AC production through inhibition of AKT and SPDEF activation in airway epithelia cells[J]. Toxins(Basel), 2021, 13(11):773. doi:10.3390/toxins13110773.
[5]	KANG M J, AHN H S, LEE S Y, et al. TGFβ1 and POSTN as biomarkers of postinfectious bronchiolitis obliterans and asthma in children[J]. Pediatr Pulmonol, 2022, 57(12):3161-3164. doi:10.1002/ppul.26139.
[6]	ZHU Y, HUANG B, JIANG G. Correlation between changes in serum YKL-40,LXRs,PPM1A,and TGF-β1 levels and airway remodeling and lung function in patients with bronchial asthma[J]. J Asthma, 2024, 61(7):698-706. doi:10.1080/02770903.2023.2301426.
[7]	中华人民共和国国家卫生健康委员会. 儿童肺炎支原体肺炎诊疗指南(2023年版)[J]. 中国合理用药探索, 2023, 20(3):16-24.
	National Health Commission of the People's Republic of China. Guidelines for Diagnosis and Treatment of Mycoplasma Pneumonae Pneumonia in Children(2023 Edition)[J]. Chinese Journal of Rational Drug Use, 2023, 20(3):16-24. doi:10.3969/j.issn.2096-3327.2023.03.003.
[8]	中国医师协会儿科医师分会儿童呼吸学组, 中华儿科杂志编辑委员会, 福棠儿童医学发展研究中心呼吸专业委员会. 6岁以下儿童喘息病因鉴别诊断和初始处理临床实践专家共识[J]. 中华儿科杂志, 2023, 61(4):301-309.
	Academic Group of Respiratory Diseases,the Society of Pediatrics,Chinese Medical Doctor Association,the Editorial Board, Chinese Journal of Pediatrics Committee on Respiratory Diseases, FuTang Research Center of Pediatric Development. Clinical practice expert consensus on differential diagnosis and initial management of wheezing in children under 6 years of age[J]. Chinese Journal of Pediatrics, 2023, 61(4):301-309. doi:10.3760/cma.j.cn112140-20230120-00052.
[9]	中华儿科杂志编辑委员会,中华医学会儿科学分会呼吸学组,中国医师协会儿科医师分会儿童呼吸专业委员会. 儿童支气管哮喘规范化诊治建议(2020年版)[J]. 中华儿科杂志, 2020, 58(9):708-717.
	The Editorial Board, Chinese Journal of Pediatrics the Subspecialty Group of Respiratory Diseases,the Society of Pediatrics, Chinese Medical Association the Children's Respiratory Professional Committee,the Society of Pediatrics of Chinese Medical Doctor Association. Recommendations for diagnosis and management of bronchial asthma in children(2020)[J]. Chinese Journal of Pediatrics, 2020, 58(9):708-717. doi:10.3760/cma.j.cn112140-20200604-00578.
[10]	CHEN J, JI F, YIN Y, et al. Time to mycoplasma pneumoniae RNA clearance for wheezy vs.non-wheezy young children with community-acquired pneumonia[J]. J Trop Pediatr, 2021, 67(1):109. doi:10.1093/tropej/fmaa109.
[11]	LIU X, WANG Y, CHEN C, et al. Mycoplasma pneumoniae infection and risk of childhood asthma:A systematic review and meta-analysis[J]. Microb Pathog, 2021, 155:104893. doi:10.1016/j.micpath.2021.104893.
[12]	AN J, LEE J H, SIM J H, et al. Serum eosinophil-derived neurotoxin better reflect asthma control status than blood eosinophil counts[J]. J Allergy Clin Immunol Pract, 2020, 8(8):2681-2688.e1. doi:10.1016/j.jaip.2020.03.035.
[13]	KIM H S, YANG H J, SONG D J, et al. Eosinophil-derived neurotoxin:An asthma exacerbation biomarker in children[J]. Allergy Asthma Proc, 2022, 43(2):133-139. doi:10.2500/aap.2022.43.210001.
[14]	KIM C K, CALLAWAY Z, PARK J S, et al. Montelukast reduces serum levels of eosinophil-derived neurotoxin in preschool asthma[J]. Allergy Asthma Immunol Res, 2018, 10(6):686-697. doi:10.4168/aair.2018.10.6.686.
[15]	RIDOLO E, PUCCIARINI F, NIZI M C, et al. Mabs for treating asthma:omalizumab,mepolizumab,reslizumab,benralizumab,dupilumab[J]. Hum Vaccin Immunother, 2020, 16(10):2349-2356. doi:10.1080/21645515.2020.1753440.
[16]	CONDE E, BERTRAND R, BALBINO B, et al. Dual vaccination against IL-4 and IL-13 protects against chronic allergic asthma in mice[J]. Nat Com mun, 2021, 12(1):2574. doi:10.1038/s41467-021-22834-5.
[17]	KIMURA Y, SHINODA M, SHINKAI M, et al. Solithromycin inhibits IL-13-induced goblet cell hyperplasia and MUC5AC,CLCA1 and ANO1 in human bronchial epithelial cells[J]. PeerJ, 2023, 11:e14695. doi:10.7717/peerj.14695.
[18]	OLAGUIBEL J M, SASTRE J, RODRÍGUEZ J M, et al. Eosinophilia induced by blocking the IL-4/IL-13 pathway:Potential mechanisms and clinical outcomes[J]. J Investig Allergol Clin Immunol, 2022, 32(3):165-180. doi:10.18176/jiaci.0823.
[19]	LUO J, CHEN H, ZHANG Q, et al. Metabolism characteristics of Mycoplasma pneumoniae infection in asthmatic children[J]. Allergy Asthma Immunol Res, 2022, 14(6):713-729. doi:10.4168/aair.2022.14.6.713.
[20]	代春英, 程丽, 朱天吉, 等. 肺炎支原体感染临床特征及TGF- β1/Smads通路变化[J]. 中华医院感染学杂志, 2023, 33(22):3423-3427.
	DAI C Y, CHENG L, ZHU T J, et al. Changes of TGF-β1/Smads pathways and clinical characteristics of patients with Mycoplasma pneumoniae infection[J]. Chin J Nosocomiol, 2023, 33(22):3423-3427. doi:10.11816/cn.ni.2023-230406.
[21]	CHENG W H, KAO S Y, CHEN C L, et al. Amphiregulin induces CCN2 and fibronectin expression by TGF-β through EGFR-dependent pathway in lung epithelial cells[J]. Respir Res, 2022, 23(1):381. doi:10.1186/s12931-022-02285-2.
[22]	CAO S, YIN H, LI X, et al. Nickel induces epithelial-mesenchymal transition in pulmonary fibrosis in mice via activation of the oxidative stress-mediated TGF-β1/Smad signaling pathway[J]. Environ Toxicol, 2024, 39(6):3597-3611. doi:10.1002/tox.24229.
[23]	邵松军, 方海燕, 叶贤伟, 等. TGFβ1/Smad3信号通路介导的赖氨酸羟化酶2活性变化在肺纤维化胶原沉积中的作用[J]. 中国病理生理杂志, 2019, 35(10):1858-1863.
	SHAO S J, FANG H Y, YE X W, et al. Role of TGFβ1/Smad3 signaling pathway-mediated lysine hydroxylase 2 activity in collagen deposition of pulmonary fibrosis[J]. Chinese Journal of Pathophysiology, 2019, 35(10):1858-1863. doi:10.3969/j.issn.1000-4718.2019.10.019.

组别	n	EDN	IL-13	TGF-β1
无喘息组	35	0.47（0.32，0.69）	0.59（0.33，1.01）	28.9（14.9，44.8）
复发喘息组	45	0.89（0.48，1.47）^a	1.14（0.46，1.79）^a	44.3（28.9，48.7）^a
哮喘组	35	1.22（0.82，1.37）^a	1.37（0.65，1.63）^a	45.1（37.3，46.5）^a
H		18.786^＊	12.826^＊	13.274^＊

组别	n	EDN	IL-13	TGF-β1
无喘息组	35	0.47（0.32，0.69）	0.59（0.33，1.01）	28.9（14.9，44.8）
复发喘息组	45	0.89（0.48，1.47）^a	1.14（0.46，1.79）^a	44.3（28.9，48.7）^a
哮喘组	35	1.22（0.82，1.37）^a	1.37（0.65，1.63）^a	45.1（37.3，46.5）^a
H		18.786^＊	12.826^＊	13.274^＊

组别			n	年龄/岁		性别（男/女）			特应性体质
无喘息组			35	6（4，8）		19/16			10（28.57）
复发喘息组			45	5（3，6）		29/16			28（62.22）
χ²或Z				1.501		0.847			8.940^＊
组别		出生情况
组别		足月/早产			顺产/剖宫产			出生体质量/g
无喘息组		29/6			19/16			3 500（3 250，3 800）
复发喘息组		37/8			19/26			3 250（3 000，3 600）
χ²或Z		0.005			1.149			2.000^＊
组别	一二级亲属过敏史						烟雾接触			住院时间≥7 d
无喘息组	11（31.43）						2（5.71）			11（31.43）
复发喘息组	26（57.78）						12（26.67）			25（55.56）
χ²	5.498^＊						5.986^＊			4.630^＊

组别			n	年龄/岁		性别（男/女）			特应性体质
无喘息组			35	6（4，8）		19/16			10（28.57）
复发喘息组			45	5（3，6）		29/16			28（62.22）
χ²或Z				1.501		0.847			8.940^＊
组别		出生情况
组别		足月/早产			顺产/剖宫产			出生体质量/g
无喘息组		29/6			19/16			3 500（3 250，3 800）
复发喘息组		37/8			19/26			3 250（3 000，3 600）
χ²或Z		0.005			1.149			2.000^＊
组别	一二级亲属过敏史						烟雾接触			住院时间≥7 d
无喘息组	11（31.43）						2（5.71）			11（31.43）
复发喘息组	26（57.78）						12（26.67）			25（55.56）
χ²	5.498^＊						5.986^＊			4.630^＊

因素	β	SE	Wald χ²	P	OR（95%CI）
EDN	1.581	0.614	6.619	0.010	4.859（1.457~16.201）
IL-13	1.060	0.507	4.377	0.036	2.887（1.069~7.792）
TGF-β1	0.041	0.020	4.054	0.044	1.042（1.001~1.085）
特应性体质	1.593	0.618	6.650	0.010	4.917（1.466~16.499）
烟雾接触	2.467	0.924	7.129	0.008	11.787（1.927~72.089）
常数项	-0.260	1.096	0.056	0.813	0.771