呼吸道合胞病毒及人鼻病毒感染致喘息急性发作婴幼儿的临床特征差异及炎性指标分析

doi:10.3969/j.issn.1006-5725.2025.15.010

Abstract

Abstract:

Objective To analyze the clinical characteristics and explore the potential mechanisms underlying acute wheezing associated with respiratory syncytial virus （RSV） and human rhinovirus （HRV） infections in infants. Methods A retrospective analysis was conducted on 560 infants who consecutively presented to the emergency department of Qingdao University Affiliated Women and Children's Hospital between January 2022 and December 2024 with acute exacerbation of wheezing caused by RSV and/or HRV infection； these infants constituted the infection group. A control group of 120 healthy infants who underwent routine physical examinations at the same hospital during the same period was also included. Multiplex PCR amplification sequencing technology was employed to detect respiratory pathogens via nucleic acid analysis. The infection group was further classified into the RSV-only group （n = 248）， the HRV-only group （n = 186）， and the co-infection group （HRV + RSV， n = 126）. One-way analysis of variance （ANOVA） was used to compare body mass index （BMI）， peripheral blood white blood cell （WBC） count， neutrophil count， lymphocyte count， C-reactive protein （CRP） levels， and concentrations of interleukin （IL）-1β， IL-6， Toll-like receptor 4 （TLR4）， NOD-like receptor protein 3 （NLRP3） inflammasome， and matrix metalloproteinase-9 （MMP-9） across the groups. Additionally， comparisons were made regarding gender distribution， severity of wheezing， history of wheezing， history of eczema， parental allergic history， oxygen supplementation requirements， and presence of concurrent pulmonary infection among the infected infants. Based on wheezing severity， the infection group was further divided into a severe wheezing group and a mild wheezing group. Clinical characteristics and biological indicators were analyzed and compared between these two groups to identify potential independent risk factors. Pearson correlation analysis was performed to evaluate the association between peripheral blood levels of IL-6， NLRP3， and MMP-9 and the severity of acute wheezing exacerbation in children. Results A one-way ANOVA indicated statistically significant differences in WBC count， neutrophil count， CRP， IL-1β， IL-6， TLR4， NLRP3， and MMP-9 levels across the study groups （all P < 0.001）. Both the RSV and co-infection groups demonstrated significantly higher rates of severe wheezing， oxygen requirement， and prolonged wheezing duration compared to the HRV group （all P < 0.05）. Among these， the co-infection group exhibited the highest oxygen requirement rate， although the duration of wheezing was shorter than that observed in the RSV group （P < 0.05）. The incidence of concurrent pulmonary infection was significantly greater in the RSV group compared to the HRV group （P < 0.05）. Additionally， the proportion of infants with a prior history of wheezing was significantly higher in the RSV group than in both the HRV and co-infection groups （P < 0.05）. Both the RSV and co-infection groups showed a significantly higher prevalence of eczema history among infants compared to the HRV group （P < 0.05）. Moreover， the co-infection group had a significantly higher proportion of parental allergic history compared with both the RSV and HRV groups （P < 0.05）. Clinical data analysis stratified by wheezing severity revealed that RSV was the most commonly detected virus among the enrolled infants， particularly in those presenting with severe wheezing （χ2 = 3.940， P = 0.002）. The severe wheezing group exhibited significantly higher rates of prior wheezing， history of eczema， parental allergy， need for oxygen supplementation， and concurrent pulmonary infections compared to the mild wheezing group （P < 0.001）. Furthermore， the duration of wheezing was significantly prolonged in the severe group relative to the mild group （t = 2.058， P = 0.040）. Levels of IL-6， NLRP3， and MMP-9 were also significantly elevated in the severe wheezing group （P < 0.05）. Multivariate logistic regression analysis revealed that RSV infection， along with elevated levels of IL-6， NLRP3， and MMP-9， were independent risk factors associated with severe wheezing （OR = 3.217， 1.023， 1.022， and 1.056， respectively； all P < 0.05）. In children with RSV/HRV infection， the severity of acute wheezing demonstrated a positive correlation with NLRP3 and MMP-9 levels （P < 0.05）. The Pearson correlation coefficient between NLRP3 and MMP-9 was r = 0.238 （P < 0.001）， indicating a weak yet statistically significant positive relationship. Conclusions RSV may provoke more severe respiratory inflammatory responses and clinical manifestations compared to HRV. Individuals with a genetic predisposition to allergies or a pre-existing history of respiratory conditions may experience heightened severity of wheezing following viral infection. The NLRP3 inflammasome may further intensify airway inflammation and remodeling through the promotion of MMP-9 release. These mechanisms may collectively contribute to the pathogenesis of acute wheezing episodes and subsequently influence the progression of respiratory diseases.

Key words: respiratory syncytial virus, human rhinovirus, wheezing, NOD-like receptor protein 3, matrix metalloproteinase-9, infants

CLC Number:

R725.6

Xiaofeng YU,Huashu LIU,Lili LEI,Gang LUO,Yingjun XU. Comparative clinical characteristics and inflammatory biomarker analysis in infants with acute wheezing induced by respiratory syncytial virus versus human rhinovirus infection[J]. The Journal of Practical Medicine, 2025, 41(15): 2355-2362.

Figures/Tables 5

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References 29

[1]	CHINRATANAPISIT S， SRITIPSUKHO P， SATDHABUDHA A， et al. Outcomes of young children hospitalized with acute wheezing［J］. Asian Pac J Allergy Immunol， 2023，41（2）：127-132.
[2]	DOSS A M A， STOKES J R. Viral Infections and Wheezing in Preschool Children［J］. Immunol Allergy Clin North Am， 2022，42（4）：727-741. doi:10.1016/j.iac.2022.05.004 doi: 10.1016/j.iac.2022.05.004
[3]	ALVAREZ I， NIU H， GUILLEN-GRIMA F， et al. Meta-analysis of prevalence of wheezing and recurrent wheezing in infants［J］. Allergol Immunopathol （Madr）， 2018，46（3）：210-217. doi:10.1016/j.aller.2016.08.011 doi: 10.1016/j.aller.2016.08.011
[4]	PADEM N， GLICK ROBISON R. The infant and toddler with wheezing［J］. Allergy Asthma Proc， 2019，40（6）：393-395. doi:10.2500/aap.2019.40.4255 doi: 10.2500/aap.2019.40.4255
[5]	ROSAS-SALAZAR C， HASEGAWA K， HARTERT T V. Progress in understanding whether respiratory syncytial virus infection in infancy causes asthma in childhood［J］. J Allergy Clin Immunol， 2023，152（4）：866-869. doi:10.1016/j.jaci.2023.08.009 doi: 10.1016/j.jaci.2023.08.009
[6]	ROSAS-SALAZAR C， CHIRKOVA T， GEBRETSADIK T， et al. Respiratory syncytial virus infection during infancy and asthma during childhood in the USA （INSPIRE）： A population-based， prospective birth cohort study［J］. Lancet， 2023，401（10389）：1669-1680. doi:10.1016/s0140-6736(23)00811-5 doi: 10.1016/s0140-6736(23)00811-5
[7]	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.
[8]	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.0000000000001495 doi: 10.1097/inf.0000000000001495
[9]	梁改丽，王琰华，王潇健，等. 婴幼儿呼吸道合胞病毒和人鼻病毒感染所致急性下呼吸道感染特征及预后分析［J］. 武警医学，2022，33（10）：857-861，865.
[10]	SARKAR S， RATHO R K， SINGH M， et al. Comparative Analysis of Epidemiology， Clinical Features， and Cytokine Response of Respiratory Syncytial and Human Metapneumovirus Infected Children with Acute Lower Respiratory Infections［J］. Jpn J Infect Dis， 2022，75（1）：56-62. doi:10.7883/yoken.jjid.2021.151 doi: 10.7883/yoken.jjid.2021.151
[11]	雷丽莉，于晓峰，王媛媛，等. 人鼻病毒感染喘息急性发作儿童外周血NLRP3和TLR4水平及临床意义［J］. 中华妇幼临床医学杂志（电子版），2024，20（4）：440-445.
[12]	SARKAR S， RATHO R K， SINGH M， et al. Role of Viral Load and Host Cytokines in Determining the Disease Severity of Respiratory Syncytial Virus-Associated Acute Lower Respiratory Tract Infections in Children［J］. Jpn J Infect Dis， 2023，76（4）：233-239. doi:10.7883/yoken.jjid.2022.673 doi: 10.7883/yoken.jjid.2022.673
[13]	李爱求，张潇潇，姜允丽，等. 学龄前儿童反复喘息的相关危险因素分析［J］. 上海交通大学学报（医学版），2022，42（10）：1435-1440.
[14]	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.
[15]	国家卫生健康委妇幼健康中心，中华预防医学会儿童保健分会，徐韬.婴幼儿重点呼吸道病毒感染性疾病预防指南［J］. 中国妇幼卫生杂志，2024，15（5）：1-6.
[16]	肖洋，杨尚栋，习文，等. 2023-2024年西安市某医院儿童呼吸道病原体流行病学特征分析［J］. 西安交通大学学报（医学版），2024，45（6）：999-1006.
[17]	SHOJI K， ASAI Y， TSUZUKI S， et al. Comparison of clinical characteristics and severity of COVID-19 with or without viral co-infection in hospitalized children［J］. J Infect Chemother， 2025，31（2）：102520. doi:10.1016/j.jiac.2024.09.009 doi: 10.1016/j.jiac.2024.09.009
[18]	LISIK D， ÖZUYGUR ERMIS S S， MILANI G P， et al. Machine learning-derived asthma and allergy trajectories in children： A systematic review and meta-analysis［J］. Eur Respir Rev， 2025，34（175）：240160. doi:10.1183/16000617.0160-2024 doi: 10.1183/16000617.0160-2024
[19]	严汝海，孙丽红，叶映彤，等. 88例婴幼儿变应性鼻炎临床特征及药物治疗后回访［J］. 实用医学杂志，2023，39（23）：3101-3105.
[20]	THAM E H， LEE A J， BEVER H V. Aeroallergen sensitization and allergic disease phenotypes in Asia［J］. Asian Pac J Allergy Immunol， 2016，34（3）：181-189.
[21]	GUO J， ZHU W， WANG H， et al. Risk factors and prognosis of recurrent wheezing in Chinese young children： A prospective cohort study［J］. Allergy Asthma Clin Immunol， 2019，15（1）：38. doi:10.1186/s13223-019-0351-4 doi: 10.1186/s13223-019-0351-4
[22]	LAUBHAHN K， SCHAUB B. From preschool wheezing to asthma： Immunological determinants［J］. Pediatr Allergy Immunol， 2023，34（10）：e14038. doi:10.1111/pai.14038 doi: 10.1111/pai.14038
[23]	KONG M， WHITLEY R， PENG N， et al. Matrix Metalloproteinase-9 Mediates RSV Infection in Vitro and in Vivo［J］. Viruses， 2015，7（8）：4230-4253. doi:10.3390/v7082817 doi: 10.3390/v7082817
[24]	沈宇茜，胡晓飞，李夏. 血清瘦素缺氧诱导因子-1α及基质金属蛋白酶-9水平与反复喘息患儿的相关性分析［J］. 中国妇幼保健，2022，37（11）：1994-1997.
[25]	张明春. 孟鲁司特钠联合普米克令舒治疗儿童难治性哮喘的临床效果［J］. 中国妇幼保健，2021，36（18）：4258-4260.
[26]	KONG M Y， CLANCY J P， PENG N， et al. Pulmonary matrix metalloproteinase-9 activity in mechanically ventilated children with respiratory syncytial virus［J］. Eur Respir J， 2014，43（4）：1086-1096. doi:10.1183/09031936.00105613 doi: 10.1183/09031936.00105613
[27]	WIECZFINSKA J， PAWLICZAK R. Anti‐fibrotic effect of ciglitazone in HRV‐induced airway remodelling cell model［J］. J Cellular Molecular Medi， 2023，27（13）：1867-1879. doi:10.1111/jcmm.17790 doi: 10.1111/jcmm.17790
[28]	WIECZFINSKA J， PAWLICZAK R. Relaxin Affects Airway Remodeling Genes Expression through Various Signal Pathways Connected with Transcription Factors［J］. IJMS， 2022，23（15）：8413. doi:10.3390/ijms23158413 doi: 10.3390/ijms23158413
[29]	WIECZFINSKA J， SITAREK P， KOWALCZYK T， et al. Curcumin modulates airway remodelling‐contributing genes—the significance of transcription factors［J］. J Cellular Molecular Medi， 2022，26（3）：736-749. doi:10.1111/jcmm.17102 doi: 10.1111/jcmm.17102

项目	健康组（n = 120）	RSV组（n = 248）	HRV组（n = 186）	合并感染组（n = 126）	F值	P值
性别/例					5.165	0.160
男	66	150	125	75
女	54	98	61	51
年龄/岁	1.60 ± 0.73	1.71 ± 0.74	1.66 ± 0.72	1.71 ± 0.76	0.728	0.535
体质量/kg	11.03 ± 1.80	11.26 ± 1.80	11.13 ± 1.85	11.22 ± 1.98	0.493	0.687
身高/m	0.82 ± 0.10	0.83 ± 0.11	0.83 ± 0.10	0.83 ± 0.11	0.480	0.696
体质量指数/（kg/m²）	16.55 ± 2.03	16.36 ± 1.90	16.20 ± 1.91	16.32 ± 2.12	0.792	0.498
白细胞计数（× 10⁹）	8.64 ± 2.62	7.59 ± 1.68^*△	8.97 ± 2.53^#	8.11 ± 2.22^△	15.327	< 0.001
淋巴细胞计数（× 10⁹）	3.14 ± 1.95	2.89 ± 1.44^△	3.33 ± 1.86^#	3.12 ± 1.65	2.464	0.061
中性粒细胞计数（× 10⁹）	5.08 ± 1.59	4.59 ± 1.71^*	4.97 ± 1.74	4.73 ± 1.69	3.073	0.027
C反应蛋白/（mg/L）	2.19 ± 1.57	9.72 ± 2.49^*	9.35 ± 2.60^*	9.28 ± 2.54^*	305.671	< 0.001
IL-1β/（ng/L）	20.35 ± 2.57	84.00 ± 2.58^*△	85.05 ± 3.19^*#	89.72 ± 1.01^*#△	516.220	< 0.001
IL-6/（ng/L）	80.47 ± 5.84	221.67 ± 26.76^*△	188.54 ± 33.49^*#	200.21 ± 34.77^*#△	708.850	< 0.001
TLR4/（ng/L）	47.16 ± 7.23	70.65 ± 6.39^*△	61.74 ± 10.25^*#	65.10 ± 10.25^*#△	222.559	< 0.001
NLRP3/（pg/mL）	79.52 ± 12.08	158.78 ± 20.56^*	155.47 ± 20.59^*	169.59 ± 18.99^*#△	604.061	< 0.001
MMP-9/（ng/mL）	123.69 ± 30.26	207.11 ± 26.08^*△	200.89 ± 22.27^*#	238.35 ± 23.17^*#△	509.254	< 0.001

项目	RSV组（n = 248）	HRV组（n = 186）	合并感染组（n = 126）	F/χ² 值	P值
重度喘息	94（37.9）	41（22.0）^?	39（31.0）^#	12.484	0.002
吸氧需求	112（45.2）	43（23.1）^?	62（49.2）^#	29.248	< 0.001
合并肺部感染	79（31.8）	34（18.3）^?	31（24.6）	10.359	0.006
喘息时间（x ± s）/d	7.60 ± 1.11	5.08 ± 0.79^?	7.03 ± 0.86^?#	418.896	< 0.001
喘息病史	103（41.5）	42（22.6）^?	21（16.7）^?	16.685	< 0.001
湿疹史	102（41.1）	34（18.3）^?	42（33.3）^?	25.772	< 0.001
父母变态反应史	46（18.5）	27（14.5）	35（27.8）^?#	8.642	0.013

项目	重度喘息组（n = 174）	轻度喘息组（n = 386）	t/χ²值	P值
病原体分类/［例（%）］			3.940	0.002
RSV	94（54.0）	154（39.9）
HRV	41（23.6）	145（37.6）
合并感染	39（22.4）	87（22.5）
喘息病史/［例（%）］	140（80.5）	26（6.74）	312.564	< 0.001
吸氧需求/［例（%）］	157（90.2）	60（15.5）	281.869	< 0.001
合并肺部感染/［例（%）］	118（67.8）	26（6.74）	234.246	< 0.001
湿疹史/［例（%）］	142（81.6）	36（9.32）	289.009	< 0.001
父母变态反应史/［例（%）］	91（52.3）	17（4.40）	176.741	< 0.001
喘息时间/d	6.76 ± 1.38	6.48 ± 1.53	2.058	0.040
IL-1β/（ng/L）	85.42 ± 3.45	85.73 ± 3.38	-1.032	0.303
IL-6/（ng/L）	210.51 ± 31.94	203.73 ± 35.14	2.173	0.030
TLR4/（ng/L）	66.92 ± 9.38	66.23 ± 9.68	0.787	0.432
NLRP3/（pg/ml）	163.46 ± 19.17	158.61 ± 21.46	2.556	0.011
MMP-9/（ng/ml）	238.33 ± 21.34	199.85 ± 22.28	19.154	< 0.001

因素	回归系数	标准误	Wald值	P值	OR值
病原体（RSV vs. 合并感染）	1.168	0.551	4.501	0.034	3.217
病原体（HRV vs. 合并感染）	0.812	0.665	1.490	0.222	2.252
喘息时间	-0.450	0.179	6.319	0.012	0.637
喘息病史	-2.669	0.659	16.390	0.000	0.069
吸氧需求	-1.633	0.563	8.402	0.004	0.195
合并肺部感染	1.038	0.587	3.126	0.077	2.823
湿疹史	-0.293	0.654	0.202	0.653	0.746
父母变态反应史	-0.765	0.525	2.123	0.145	0.465
IL-6	0.023	0.006	14.597	0.000	1.023
NLRP3	0.022	0.009	5.429	0.020	1.022
MMP-9	0.055	0.008	42.432	0.000	1.056
常量	-16.275	3.030	28.853	0.000	< 0.001

项目	r值	P值
IL-6	0.081	0.054
NLRP3	0.108	0.011
MMP-9	0.618	< 0.001

Comparative clinical characteristics and inflammatory biomarker analysis in infants with acute wheezing induced by respiratory syncytial virus versus human rhinovirus infection

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