| 19 | 0 | 360 |
| 下载次数 | 被引频次 | 阅读次数 |
分析哮喘患儿呼吸道病毒感染的高危因素及其与微RNA-21(miR-21)、基质金属蛋白酶-9(MMP-9)和CD4~+T细胞亚群关系。选取我院2023年6月至2025年5月收治的112例哮喘患儿为研究对象,回顾性分析其临床资料,根据病毒检测结果将其分为病毒感染组(n=56)和非感染组(n=56),采用Logistic回归模型分析哮喘患儿呼吸道病毒感染的高危因素及与miR-21、MMP-9和CD4~+T细胞亚群的关系,采用R语言rms程序包建立Nomogram,采用受试者工作特征(ROC)曲线、校准曲线及决策曲线(DCA)评估模型准确性。本研究纳入的112例哮喘患儿中,56例呼吸道病毒检测为阳性,阳性率为50.00%。56例感染患儿中,病毒类型构成比居前三位的分别是呼吸道合胞病毒(RSV)(41.07%)、腺病毒(ADV)(28.57%)、副流感病毒Ⅲ型(PIVⅢ)(8.93%)和流感病毒A型(ⅣA)(8.93%)。logistic回归模型;多因素结果显示:过敏体质、miR-21(高表达)、MMP-9(高表达)、CD4~+T细胞亚群(低表达)均是哮喘患儿并发呼吸道病毒感染的高危因素(P<0.05)。风险列线图模型显示:上述高危因素均可预测哮喘患儿并发呼吸道病毒感染,具有统计学意义(P<0.05),该列线图C-index为0.992。ROC曲线显示:哮喘患儿并发呼吸道病毒感染预测体系AUC为0.992(95%CI:0.982~1.000),灵敏度为0.982,特异度为0.964;校准曲线显示:H-L拟合优度检验结果证实(χ2=0.581,P=0.999)该模型预测概率与实际概率无显著性,表明该模型预测准确度较高;DCA曲线显示:该模型预测风险阈值>0.03,可获得较高净收益。过敏体质、miR-21(高表达)、MMP-9(高表达)、CD4~+T细胞亚群(低表达)均是哮喘患儿并发呼吸道病毒感染的高危因素,临床需高度关注,尽早识别高危患儿并进行干预,以降低呼吸道病毒感染风险。
Abstract:Objective To investigate the high-risk factors for respiratory viral infection in children with asthma and to explore their associations with microRNA-21(miR-21), matrix metalloproteinase-9(MMP-9), and CD4+ T-cell subsets. Methods A total of 112 children with asthma admitted to our hospital between June 2023 and May 2025 were retrospectively enrolled. According to viral detection results, patients were divided into a viral infection group(n = 56) and a non-infection group(n = 56). Logistic regression analysis was performed to identify risk factors for respiratory viral infection and to evaluate their associations with miR-21, MMP-9, and CD4+ T-cell subsets. A nomogram prediction model was constructed using the rms package in R. The predictive performance of the model was evaluated using receiver operating characteristic(ROC) curves, calibration curves, and decision curve analysis(DCA). Results Among the 112 children with asthma included in this study, 56 tested positive for respiratory viruses, yielding a positivity rate of 50.00%. Among the infected cases, the most frequently detected viruses were respiratory syncytial virus(RSV)(41.07%), adenovirus(ADV)(28.57%), parainfluenza virus type III(PIV-III)(8.93%), and influenza A virus(IVA)(8.93%). Multivariate logistic regression analysis showed that allergic constitution, high expression of miR-21, high expression of MMP-9, and decreased CD4+ T-cell subsets were independent risk factors for respiratory viral infection in children with asthma(P < 0.05). The nomogram model indicated that these risk factors could effectively predict respiratory viral infection in children with asthma(P < 0.05), with a concordance index(Cindex) of 0.992. The ROC curve showed that the predictive model achieved an area under the curve(AUC) of 0.992(95% CI: 0.982 – 1.000), with a sensitivity of 0.982 and a specificity of 0.964. The calibration curve demonstrated good agreement between predicted and observed probabilities, as confirmed by the Hosmer –Lemeshow goodness-of-fit test (χ2 = 0.581, P = 0.999), indicating high predictive accuracy of the model. The DCA curve showed that when the risk threshold exceeded 0.03, the model yielded a higher net clinical benefit. Conclusion Allergic constitution, high expression of miR-21, high expression of MMP-9, and decreased CD4+ T-cell subsets are significant risk factors for respiratory viral infection in children with asthma. Early identification of high-risk patients and timely clinical intervention may help reduce the risk of respiratory viral infection.
[1]Agarwal T, Peterson R, Jimenez G, et al. Impact of effect modification of type 2 inflammation and sex on asthma exacerbation rates[J]. CHEST Pulm, 2025, 3(3):100123. DOI:10. 1016/j. chpulm. 2024. 100123.
[2]Zhang Y, Hai Y, Song B, et al. Screening and validation of potential biomarkers of immune cells in childhood asthma patients via Mendelian randomization and machine learning[J]. J Inflamm Res, 2025, 18:2583-2600. DOI:10. 2147/JIR. S498017.
[3]Penders Y, Brusselle G, Falsey AR, et al. Burden of respiratory syncytial virus disease in adults with asthma and chronic obstructive pulmonary disease:a systematic literature review[J]. Curr Allergy Asthma Rep, 2025,25(1):14. DOI:10. 1007/s11882-025-01194-w.
[4]肖荣,肖丽萍,王美华,等.血清炎症因子及免疫功能指标在慢性乙型肝炎病毒感染中的应用进展[J].病毒学报,2025, 41(5):1600-1608. DOI:10. 13242/j.cnki. bingduxuebao. 250208.
[5]Kim RY, Horvat JC, Pinkerton JW, et al. microRNA-21 drives severe, steroid-insensitive experimental asthma by amplifying phosphoinositide 3-kinasemediated suppression of histone deacetylase 2[J]. J Allergy Clin Immunol, 2017, 139(2):519-532. DOI:10. 1016/j. jaci. 2016. 04. 038.
[6]Quan J, Xie D, Li Z, et al. Luteolin alleviates airway remodeling in asthma by inhibiting the epithelialmesenchymal transition via β-catenin regulation[J].Phytomedicine, 2024, 135:156090. DOI:10. 1016/j.phymed. 2024. 156090.
[7]Gaberino CL, Altman MC, Gill MA, et al.Dysregulation of airway and systemic interferon responses promotes asthma exacerbations in urban children[J]. J Allergy Clin Immunol, 2025, 155(5):1499-1509. DOI:10. 1016/j. jaci. 2024. 12. 1090.
[8]中华医学会呼吸病学分会哮喘学组.支气管哮喘防治指南(2020年版)[J].中华结核和呼吸杂志,2020, 43(12):1023-1048. DOI:10. 3760/cma. j. cn112147-20200618-00721.
[9]Arslan Bozdag L, A?ik L, Ersoy HE, et al. PDCD4and MIR-21 are promising biomarkers in the follow-up of OED in liquid biopsies[J]. Oral Dis, 2024, 30(6):3873-3883. DOI:10. 1111/odi. 14817.
[10]Wozniak-Kosek A, Kosek J, Zielnik-Jurkiewicz B.Detection of respiratory tract pathogens with molecular biology methods[J]. Adv Exp Med Biol, 2015, 835:9-13. DOI:10. 1007/5584_2014_30.
[11]De Leeuw E, Justesen JF, Bosteels C, et al. Maternal allergy and neonatal RSV infection synergize via FcRmediated allergen uptake to promote the development of asthma in early life[J]. Sci Immunol, 2025, 10(113):eadz4626. DOI:10. 1126/sciimmunol. adz4626.
[12]Deng S, Cong B, Edgoose M, et al. Risk factors for respiratory syncytial virus-associated acute lower respiratory infection in children under 5 years:an updated systematic review and meta-analysis[J]. Int J Infect Dis, 2024, 146:107125. DOI:10. 1016/j.ijid. 2024. 107125.
[13]韩倩倩,苏玢,冯勇.血清LMR、hs-CRP及MMP-9与耳带状疱疹病毒感染并发面瘫的相关性研究[J].病毒学报,2025, 41(1):148-154. DOI:10. 13242/j. cnki.bingduxuebao. 004660.
[14]Elbehidy RM, Youssef DM, El-Shal AS, et al.microRNA-21 as a novel biomarker in diagnosis and response to therapy in asthmatic children[J]. Mol Immunol, 2016, 71:107-114. DOI:10. 1016/j.molimm. 2015. 12. 015.
[15]Xue B, Zhou A, Zhong Y, et al. MMP-9 regulates disulphide isomerase activity of TGM2 to enhance fusion glycoprotein-mediated syncytium formation of respiratory syncytial virus[J]. Protein Cell, 2026, 17(1):59-76. DOI:10. 1093/procel/pwaf063.
[16]Alobaidi AH, Alsamarai AM, Alsamarai MA.Inflammation in asthma pathogenesis:role of T cells,macrophages, epithelial cells and type 2 inflammation[J]. Antiinflamm Antiallergy Agents Med Chem,2021, 20(4):317-332. DOI:10. 2174/1871523020666210920100707.
[17]Arimura K, Kan-O K, Sato Y, et al. Age-dependent risk of bronchial asthma exacerbation in respiratory syncytial virus co-infection[J]. Lung, 2025, 203(1):91. DOI:10. 1007/s00408-025-00847-x.
[18]乔晓丞,申娜,郭东梅.小儿咳嗽变异性哮喘合并呼吸道合胞病毒感染的病毒载量与血清标志物的相关性分析[J].病毒学报,2025, 41(3):813-818. DOI:10. 13242/j. cnki. bingduxuebao. 240311.
[19]Picado C, Garcia de la Fuente A, Arismendi E, et al.Next decade research in asthma:broad omics-based exploration versus targeted airway epithelium studies[J]. J Clin Med, 2025, 14(22):8186. DOI:10. 3390/jcm14228186.
[20]Pei H, Luo H. Predictive clinical indicators of refractory Mycoplasma pneumoniae pneumonia in children:a retrospective cohort study[J]. Medicine, 2024, 103(34):e39375. DOI:10. 1097/MD. 0000000000039375.
[21]Zhang L, Jia X, Zhang Z, et al. CeRNA network analysis reveals potential key miRNAs and target genes in COVID-19-related chronic obstructive pulmonary disease[J]. Appl Biochem Biotechnol, 2024, 196(7):4303-4316. DOI:10. 1007/s12010-023-04773-7.
[22]Wolosowicz M, Prokopiuk S, Kaminski TW. Matrix metalloproteinase-9(MMP-9)as a therapeutic target:insights into molecular pathways and clinical applications[J]. Pharmaceutics, 2025, 17(11):1425. DOI:10. 3390/pharmaceutics17111425.
[23]Beigelman A, Goss CW, Wang J, et al. Azithromycin therapy in infants hospitalized for respiratory syncytial virus bronchiolitis:Airway matrix metalloproteinase-9levels and subsequent recurrent wheeze[J]. Ann Allergy Asthma Immunol, 2024, 132(5):623-629. DOI:10. 1016/j. anai. 2024. 01. 001.
[24]杨宣叶,胡欣妍,高明阳,等. CD4+和CD8+T细胞在抗流感病毒免疫中的重要作用[J].病毒学报,2024,40(1):206-214. DOI:10. 13242/j. cnki.bingduxuebao. 004422.
[25]Aili A, Wang Y, Shang Y, et al. LPG 18:0 is a general biomarker of asthma and inhibits the differentiation and function of regulatory T-cells[J]. Eur Respir J, 2024, 64(6):2301752. DOI:10. 1183/13993003. 01752-2023.
基本信息:
中图分类号:R725.6
引用信息:
[1]周晓燕,徐桂林,李亚楠,等.哮喘患儿呼吸道病毒感染的高危因素及其与miR-21,MMP-9和CD4~+T细胞亚群关系[J].病毒学报().
基金信息:
湖北省卫健委联合科研项目(项目号:XS-2024065),题目:健脾助长方合并生长激素对GHD小鼠的身长改善及肝脏组织GHR和IGF-1mRNA表达的影响
2026-06-09
2026-06-09
2026-06-09