血清14-3-3β蛋白联合呼出气一氧化氮及常规通气肺功能参数对儿童支气管哮喘的诊断效能

李舒芳; 郭广恩; 杨月琴; 熊晓曼; 郑世威; 谢雪丽; 张艳丽

doi:10.7499/j.issn.1008-8830.2401058

PDF(628 KB)

HTML

中国当代儿科杂志 ›› 2024, Vol. 26 ›› Issue (7) : 723-729. DOI: 10.7499/j.issn.1008-8830.2401058

论著·临床研究

血清14-3-3β蛋白联合呼出气一氧化氮及常规通气肺功能参数对儿童支气管哮喘的诊断效能

李舒芳, 郭广恩, 杨月琴, 熊晓曼, 郑世威, 谢雪丽, 张艳丽

作者信息 +

Diagnostic efficacy of serum 14-3-3β protein combined with fractional exhaled nitric oxide and conventional ventilatory lung function parameters for bronchial asthma in children

LI Shu-Fang, GUO Guang-En, YANG Yue-Qin, XIONG Xiao-Man, ZHENG Shi-Wei, XIE Xue-Li, ZHANG Yan-Li

Author information +

文章历史 +

摘要

目的探讨血清14-3-3β蛋白联合呼出气一氧化氮（fractional exhaled nitric oxide, FeNO）及常规通气肺功能参数对儿童支气管哮喘（简称“哮喘”）的诊断效能。方法前瞻性纳入136例初次诊断为哮喘且处于急性发作期的儿童为哮喘组，选择同期85例健康体检儿童为健康对照组，比较两组血清14-3-3β蛋白浓度的差异，分析血清14-3-3β蛋白与临床指标的相关性，评估14-3-3β蛋白联合FeNO及常规通气肺功能参数对儿童哮喘的诊断效能。结果哮喘组血清14-3-3β蛋白浓度高于健康对照组（P<0.001）。血清14-3-3β蛋白与中性粒细胞百分比、血清总免疫球蛋白E呈正相关，与常规通气肺功能参数呈负相关（P<0.05）。联合指标交叉验证显示14-3-3β蛋白+FeNO+用力呼出75%肺活量的呼气流量占预测值百分比预测哮喘的曲线下面积为0.948，灵敏度和特异度分别为88.9%和93.7%，具有较好的诊断效能（P<0.001），模型的外推性最好。结论血清14-3-3β蛋白联合FeNO、用力呼出75%肺活量的呼气流量占预测值百分比可以显著提高儿童哮喘的诊断效能。

Abstract

Objective To explore the diagnostic efficacy of serum 14-3-3β protein combined with fractional exhaled nitric oxide (FeNO) and conventional ventilatory lung function parameters in diagnosing bronchial asthma (referred to as "asthma") in children. Methods A prospective study included 136 children initially diagnosed with asthma during an acute episode as the asthma group, and 85 healthy children undergoing routine health checks as the control group. The study compared the differences in serum 14-3-3β protein concentrations between the two groups, analyzed the correlation of serum 14-3-3β protein with clinical indices, and evaluated the diagnostic efficacy of combining 14-3-3β protein, FeNO, and conventional ventilatory lung function parameters for asthma in children. Results The concentration of serum 14-3-3β protein was higher in the asthma group than in the control group (P<0.001). Serum 14-3-3β protein showed a positive correlation with the percentage of neutrophils and total serum immunoglobulin E, and a negative correlation with conventional ventilatory lung function parameters (P<0.05). Cross-validation of combined indices showed that the combination of 14-3-3β protein, FeNO, and the percentage of predicted value of forced expiratory flow at 75% of lung volume had an area under the curve of 0.948 for predicting asthma, with a sensitivity and specificity of 88.9% and 93.7%, respectively, demonstrating good diagnostic efficacy (P<0.001). The model had the best extrapolation. Conclusions The combination of serum 14-3-3β protein, FeNO, and the percentage of predicted value of forced expiratory flow at 75% of lung volume can significantly improve the diagnostic efficacy for asthma in children. Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 723-729

导出引用

李舒芳, 郭广恩, 杨月琴, 熊晓曼, 郑世威, 谢雪丽, 张艳丽. 血清14-3-3β蛋白联合呼出气一氧化氮及常规通气肺功能参数对儿童支气管哮喘的诊断效能[J]. 中国当代儿科杂志. 2024, 26(7): 723-729 https://doi.org/10.7499/j.issn.1008-8830.2401058

LI Shu-Fang, GUO Guang-En, YANG Yue-Qin, XIONG Xiao-Man, ZHENG Shi-Wei, XIE Xue-Li, ZHANG Yan-Li. Diagnostic efficacy of serum 14-3-3β protein combined with fractional exhaled nitric oxide and conventional ventilatory lung function parameters for bronchial asthma in children[J]. Chinese Journal of Contemporary Pediatrics. 2024, 26(7): 723-729 https://doi.org/10.7499/j.issn.1008-8830.2401058

参考文献

1 Porsbjerg C, Melén E, Lehtim?ki L, et al. Asthma[J]. Lancet, 2023, 401(10379): 858-873. PMID: 36682372. DOI: 10.1016/S0140-6736(22)02125-0.
2 Asher MI, García-Marcos L, Pearce NE, et al. Trends in worldwide asthma prevalence[J]. Eur Respir J, 2020, 56(6): 2002094. PMID: 32972987. DOI: 10.1183/13993003.02094-2020.
3 Asher MI, Rutter CE, Bissell K, et al. Worldwide trends in the burden of asthma symptoms in school-aged children: Global Asthma Network Phase I cross-sectional study[J]. Lancet, 2021, 398(10311): 1569-1580. PMID: 34755626. PMCID: PMC8573635. DOI: 10.1016/S0140-6736(21)01450-1.
4 Martin J, Townshend J, Brodlie M. Diagnosis and management of asthma in children[J]. BMJ Paediatr Open, 2022, 6(1): e001277. PMID: 35648804. PMCID: PMC9045042. DOI: 10.1136/bmjpo-2021-001277.
5 刘开来. 呼出气一氧化氮、总免疫球蛋白E及血嗜酸性粒细胞在儿童哮喘诊断中的价值[J]. 中国中西医结合儿科学, 2023, 15(3): 224-228. DOI: 10.3969/j.issn.1674-3865.2023.03.010.
6 Loewenthal L, Menzies-Gow A. FeNO in asthma[J]. Semin Respir Crit Care Med, 2022, 43(5): 635-645. PMID: 35253144. DOI: 10.1055/s-0042-1743290.
7 Fraser A, Simpson R, Turner S. Use of exhaled nitric oxide in the diagnosis and monitoring of childhood asthma: myth or maxim?[J]. Breathe (Sheff), 2023, 19(4): 220236. PMID: 38125803. PMCID: PMC10729813. DOI: 10.1183/20734735.0236-2022.
8 Breiteneder H, Peng YQ, Agache I, et al. Biomarkers for diagnosis and prediction of therapy responses in allergic diseases and asthma[J]. Allergy, 2020, 75(12): 3039-3068. PMID: 32893900. PMCID: PMC7756301. DOI: 10.1111/all.14582.
9 Wang W, Shakes DC. Molecular evolution of the 14-3-3 protein family[J]. J Mol Evol, 1996, 43(4): 384-398. PMID: 8798343. DOI: 10.1007/BF02339012.
10 Asdaghi N, Kilani RT, Hosseini-Tabatabaei A, et al. Extracellular 14-3-3 from human lung epithelial cells enhances MMP-1 expression[J]. Mol Cell Biochem, 2012, 360(1-2): 261-270. PMID: 21948273. DOI: 10.1007/s11010-011-1065-1.
11 何淑娟, 陈雅, 童夏生, 等. 布地奈德对哮喘大鼠肺组织14-3-3蛋白及14-3-3β mRNA表达的影响[J]. 儿科药学杂志, 2016, 22(6): 5-7. DOI: 10.13407/j.cnki.jpp.1672-108X.2016.06.002.
12 Wang D, Rao L, Cui Y, et al. Serum 14-3-3β protein: a new biomarker in asthmatic patients with acute exacerbation in an observational study[J]. Allergy Asthma Clin Immunol, 2021, 17(1): 104. PMID: 34627360. PMCID: PMC8502409. DOI: 10.1186/s13223-021-00608-4.
13 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. PMID: 32872710. DOI:10.3760/cma.j.cn112140-20200604-00578.
14 Beydon N, Davis SD, Lombardi E, et al. An official American Thoracic Society/European Respiratory Society statement: pulmonary function testing in preschool children[J]. Am J Respir Crit Care Med, 2007, 175(12): 1304-1345. PMID: 17545458. DOI: 10.1164/rccm.200605-642ST.
15 American Thoracic Society, European Respiratory Society. ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005[J]. Am J Respir Crit Care Med, 2005, 171(8): 912-930. PMID: 15817806. DOI: 10.1164/rccm.200406-710ST.
16 He X, Frey E. ROC, LROC, FROC, AFROC: an alphabet soup[J]. J Am Coll Radiol, 2009, 6(9): 652-655. PMID: 19720362. DOI: 10.1016/j.jacr.2009.06.001.
17 Jutel M, Mosnaim GS, Bernstein JA, et al. The one health approach for allergic diseases and asthma[J]. Allergy, 2023, 78(7): 1777-1793. PMID: 37119496. DOI: 10.1111/all.15755.
18 Pelaia C, Vatrella A, Crimi C, et al. Clinical relevance of understanding mitogen-activated protein kinases involved in asthma[J]. Expert Rev Respir Med, 2020, 14(5): 501-510. PMID: 32098546. DOI: 10.1080/17476348.2020.1735365.
19 Fu H, Subramanian RR, Masters SC. 14-3-3 proteins: structure, function, and regulation[J]. Annu Rev Pharmacol Toxicol, 2000, 40: 617-647. PMID: 10836149. DOI: 10.1146/annurev.pharmtox.40.1.617.
20 Kataki A, Karagiannidis I, Memos N, et al. Host's endogenous caveolin-1 expression is downregulated in the lung during sepsis to promote cytoprotection[J]. Shock, 2018, 50(2): 199-208. PMID: 28957875. DOI: 10.1097/SHK.0000000000001005.
21 Fainardi V, Esposito S, Chetta A, et al. Asthma phenotypes and endotypes in childhood[J]. Minerva Med, 2022, 113(1): 94-105. PMID: 33576199. DOI: 10.23736/S0026-4806.21.07332-8.
22 Shilovskiy IP, Kovchina VI, Timotievich ED, et al. Role and molecular mechanisms of alternative splicing of Th2-cytokines IL-4 and IL-5 in atopic bronchial asthma[J]. Biochemistry (Mosc), 2023, 88(10): 1608-1621. PMID: 38105028. DOI: 10.1134/S0006297923100152.
23 Li F, Huang Y, Huang YY, et al. MicroRNA-146a promotes IgE class switch in B cells via upregulating 14-3-3σ expression[J]. Mol Immunol, 2017, 92: 180-189. PMID: 29101850. DOI: 10.1016/j.molimm.2017.10.023.
24 Hong L, Herjan T, Bulek K, et al. Mechanisms of corticosteroid resistance in type 17 asthma[J]. J Immunol, 2022, 209(10): 1860-1869. PMID: 36426949. PMCID: PMC9666330. DOI: 10.4049/jimmunol.2200288.
25 Jo A, Kim DW. Neutrophil extracellular traps in airway diseases: pathological roles and therapeutic implications[J]. Int J Mol Sci, 2023, 24(5): 5034. PMID: 36902466. PMCID: PMC10003347. DOI: 10.3390/ijms24055034.
26 Flinkman E, V?h?talo I, Tuomisto LE, et al. Association between blood eosinophils and neutrophils with clinical features in adult-onset asthma[J]. J Allergy Clin Immunol Pract, 2023, 11(3): 811-821.e5. PMID: 36473624. DOI: 10.1016/j.jaip.2022.11.025.
27 Wang D, Rao L, Lei H, et al. Clinical significance of serum levels of 14-3-3β protein in patients with stable chronic obstructive pulmonary disease[J]. Sci Rep, 2023, 13(1): 4861. PMID: 36964173. PMCID: PMC10039013. DOI: 10.1038/s41598-023-32096-4.
28 Gao K, Tang W, Li Y, et al. Front-signal-dependent accumulation of the RHOA inhibitor FAM65B at leading edges polarizes neutrophils[J]. J Cell Sci, 2015, 128(5): 992-1000. PMID: 25588844. PMCID: PMC4342581. DOI: 10.1242/jcs.161497.
29 Jendzjowsky NG, Kelly MM. The role of airway myofibroblasts in asthma[J]. Chest, 2019, 156(6): 1254-1267. PMID: 31472157. DOI: 10.1016/j.chest.2019.08.1917.
30 Li J, Gong X. 14-3-3β is necessary in the regulation of polarization and directional migration of alveolar myofibroblasts by lipopolysaccharide[J]. Exp Lung Res, 2020, 46(1/2): 1-10. PMID: 31920140. DOI: 10.1080/01902148.2019.1711464.
31 Global Initiative for Asthma. Pocket guide for asthma management and prevention[EB/OL]. [2023-12-22]. https://ginasthma. org/pocket-guide-for-asthma-management-and-preven-tion/.
32 Comberiati P, McCormack K, Malka-Rais J, et al. Proportion of severe asthma patients eligible for mepolizumab therapy by age and age of onset of asthma[J]. J Allergy Clin Immunol Pract, 2019, 7(8): 2689-2696.e2. PMID: 31201938. DOI: 10.1016/j.jaip.2019.05.053.
33 Cottini M, Lombardi C, Berti A, et al. Small-airway dysfunction in paediatric asthma[J]. Curr Opin Allergy Clin Immunol, 2021, 21(2): 128-134. PMID: 33620881. DOI: 10.1097/ACI.0000000000000728.
34 Calzetta L, Aiello M, Frizzelli A, et al. Small airways in asthma: from bench-to-bedside[J]. Minerva Med, 2022, 113(1): 79-93. PMID: 33496163. DOI: 10.23736/S0026-4806.21.07268-2.