急性下呼吸道感染患儿病原菌分布特征及血清8GOHdG和METRNβ水平变化的研究

Study on distribution characteristics of pathogenic bacteria and changes in serum 8GOHdG and METRNβ levels in children with acute lower respiratory tract infection

摘要

目的 探讨急性下呼吸道感染(ALRTI)患儿病原菌分布特征及血清8G羟基脱氧鸟苷酸(8GOHdG)和镍纹蛋白样β(METRNβ)水平的变化。方法 选取2022年2月至2023年3月期间在电子科技大学医学院附属妇女儿童医院/成都市妇女儿童中心医院进行治疗的195例ALRTI患儿为ALRTI组,根据病情程度分为轻度组(129例)与重度组(66例),根据感染情况分为革兰氏阴性菌感染组(128例)、革兰氏阳性菌感染组(57例)、真菌感染组(10例);另选取同期体检健康的100例儿童为对照组.采集所有患儿的痰液标本检测病原菌分布情况;采用酶联免疫吸附实验检测血清8GOHdG和METRNβ水平;采用Spearman法分析ALRTI患儿血清8GOHdG和METRNβ水平与病情程度的相关性;采用受试者工作特征(ROC)曲线分析血清8GOHdG和METRNβ水平对ALRTI患儿病情程度的诊断价值。结果 经培养共分离出病原菌258株,其中革兰氏阴性菌179株,占69.38%;革兰氏阳性菌69株,占26.74%;真菌10株,占3.88%.ALRTI组血清8GOHdG、METRNβ水平均显著高于对照组,经比较差异均有统计学意义(t值分别为54.692、29.143,P<0.05).革兰氏阴性菌感染组、革兰氏阳性菌感染组、真菌感染组血清8GOHdG和METRNβ水平比较,差异均有统计学意义(F值分别为152.077、9.831,P<0.05).重度组血清8GOHdG、METRNβ水平均显著高于轻度组,经比较差异均有统计学意义(t值分别为8.935、8.336,P<0.05).血清8GOHdG和METRNβ水平与病情程度均呈正相关(r值分别为0.682、0.633,P<0.05).血清8GOHdG和METRNβ及二者联合诊断ALRTI患儿病情程度的曲线下面积(AUC)分别为0.836、0.828、0.926,二者联合较血清8GOHdG、METRNβ单项诊断更具诊断效能(Z二者联合与8GOHdG=3.793、Z二者联合与METRNβ=4.296,P<0.05)。结论 ALRTI患儿病原菌分布以革兰氏阴性菌为主,血清8GOHdG和METRNβ水平均升高,二者与病情程度密切相关,可能成为检测ALRTI患儿病情程度的血清学标志物,且两指标联合检测更具诊断效能.

Abstract

Objective To investigate distribution characteristics of pathogenic bacteria and changes in serum 8G hydroxy-2'-deoxyguanosine (8GOHdG) and METRNL/Meteorin-like protein β (METRNβ) levels in children with acute lower respiratory tract infection (ALRTI). Methods From February 2022 to March 2023, 195 children with ALRTI who were treated in our hospital were selected as ALRTI group, and they were divided into mild ALRTI group (129 cases) and severe ALRTI group (66 cases) according to severity of the disease by criteria of acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ). According to pathogen of ALRTI, the children were divided into Gram-negative bacteria infection group (128 cases), Gram-positive bacteria infection group (57 cases), and fungi infection group (10 cases) again. Additionally, 100 healthy children who underwent physical examination in the same period were selected as control group. All sputum samples from the affected children were collected to test distribution of pathogens. Enzyme linked immunosorbent assay (ELIZA) was applied to detect serum levels of 8GOHdG and METRNβ. Spearman correlation analysis was applied to analyze correlations between serum 8GOHdG, METRNβ levels and severity of ALRTI in children. Receiver operating characteristic (ROC) curve was applied to analyze diagnostic values of serum 8GOHdG and METRNβ levels for severity of ALRTI in children. Results A total of 258 strains of pathogenic bacteria were isolated from ALRTI patients through pathogen culture, including 179 strains of Gram-negative bacteria (69.38%), 69 strains of Gram-positive bacteria (26.74%) and 10 strains of fungi (3.88%). Compared with the control group, the serum levels of 8GOHdG and METRNβ in the ALRTI group were significantly higher, and the differences were significant (t=54.692 and 29.143 respectively, both P<0.05). There were significant differences in serum levels of 8GOHdG and METRNβ levels among the Gram-negative bacteria infection group, the Gram-positive bacteria infection group and the fungi infection group (F=152.077 and 9.831 respectively, both P<0.05), in detail, the serum 8GOHdG and METRNβ levels in the Gram-negative bacteria infection group and the Gram-positive bacteria infection group were higher than those in the fungi infection group (both P<0.05), and the serum 8GOHdG and METRNβ levels in the Gram-negative bacteria infection group were higher than those in the Gram-positive bacteria infection group (both P<0.05). Moreover, the serum levels of 8GOHdG and METRNβ in the severe ALRTI group were higher than those in the mild ALRTI group (t=8.935 and 8.336 respectively, both P<0.05). The correlation analysis showed that the serum levels of 8GOHdG and METRNβ were positively correlated with severity of the disease (r=0.682 and 0.633 respectively, both P<0.05). The areas under the curve (AUCs) of serum 8GOHdG and METRNβ levels, and their combination for diagnosing severity of ALRTI in children were 0.836, 0.828 and 0.926 respectively, suggesting that the combination of the two indexes was superior to single serum 8GOHdG and single serum METRNβ alone (Zcombination-8GOHdG=3.793, Zcombination-METRNβ=4.296, all P<0.05). Conclusion The pathogenic bacteria in children with ALRTI are mainly Gram-negative strains, when, the serum levels of 8GOHdG and METRNβ elevate together, which are closely related to severity of the disease. Therefore, they may become serological markers for judging severity of ALRTI in children, and combined detection of the two indexes has more diagnostic efficacy.

关键词

儿童 / 急性下呼吸道感染 / 8G羟基脱氧鸟苷酸 / 镍纹蛋白样β / 病原菌分布特征 / 病情程度

Key words

children / acute lower respiratory tract infection / 8G hydroxy-2'-deoxyguanosine / METRNL/Meteorin-like protein β / distribution characteristics of pathogenic bacteria / severity of the disease

参考文献

[1] Buonsenso D, Musolino A, Ferro V, et al. Role of lung ultrasound for the etiological diagnosis of acute lower respiratory tract infection (ALRTI) in children: a prospective study[J]. J Ultrasound, 2022, 25(2): 185-197.

[2] 曹文珮, 马晶, 李娟生, 等. 甘肃省儿童急性下呼吸道感染病原流行病学特征[J]. 中华疾病控制杂志, 2020, 24(2): 128-133.

[3] Lipshaw MJ, Eckerle M, Florin TA, et al. Antibiotic use and outcomes in children in the emergency department with suspected pneumonia[J]. Pediatrics, 2020, 145(4): e20193138.

[4] Coskun F Y, Taysı S, Kayıkçıoğlu M. Can serum 8-hydroxy-2'-deoxyguanosine levels reflect the severity of pulmonary arterial hypertension?[J]. Rev Assoc Med Bras (1992), 2021, 67(10): 1437-1442.

[5] Cao LF, Cheng JY, Xu Z, et al. Serum 8-Hydroxydeoxyguanosine is a potential indicator for the severity and prognosis in patients with community-acquired pneumonia: a prospective cohort study[J]. J Immunol, 2022, 208(2): 321-327.

[6] Gao X, Leung TF, Wong GW, et al. Meteorin-β/Meteorin like/IL-41 attenuates airway inflammation in house dust mite-induced allergic asthma[J]. Cell Mol Immunol, 2022, 19(2): 245-259.

[7] 江载芳, 申昆玲, 沈颖. 诸福棠实用儿科学[M]. 北京: 人民卫生出版社, 2015: 1251-1288.

[8] 何亚妮, 曾苹, 徐娟. APACHEⅡ评分与PEWS评分对急性呼吸窘迫综合征患儿预后的预测价值探究[J]. 中国医学前沿杂志(电子版), 2018, 10(6): 161-164.

[9] 王俭, 万光平, 李益, 等. 小儿急性呼吸道感染PA、SAA、CD64、sCD14-ST水平及其诊断价值[J]. 中华医院感染学杂志, 2023, 33(23): 3659-3663.

[10] 赵光宇, 王欣, 田恬. 维生素A水平与儿童急性下呼吸道感染的相关性[J]. 中国妇幼健康研究, 2022, 33(5): 35-40.

[11] 钟小珍, 韦洁宏, 莫红梅, 等. 2639例下呼吸道感染患儿病原菌分布及耐药性分析[J]. 海南医学, 2018, 29(14): 1984-1987.

[12] 郑佳明, 赵志伟. 厦门海沧566例下呼吸道感染患儿痰培养阳性标本病原菌构成及耐药分析[J]. 海峡药学, 2023, 35(5): 83-86.

[13] 高巍, 柴丽, 方昆. 某医院急性下呼吸道感染患儿病原菌分布特征分析[J]. 实用医技杂志, 2021, 28(9): 1105-1107.

[14] Hemmendinger M, Sauvain JJ, Hopf NB, et al. Challenges in quantifying 8-OHdG and 8-Isoprostane in exhaled breath condensate[J]. Antioxidants (Basel), 2022, 11(5): 830.

[15] 于晨, 董超然, 张照辉, 等. 8-羟基脱氧鸟嘌呤作为DNA氧化损伤标志物的研究现状[J]. 中国临床药理学杂志, 2017, 33(13): 1267-1270.

[16] 郑海茹, 吴熊军, 许文彬. 慢性阻塞性肺疾病急性加重期谷胱甘肽过氧化酶、丙二醛、8-羟基脱氧鸟苷测定价值探讨[J]. 实用医院临床杂志, 2023, 20(3): 58-62.

[17] 王明明, 刘灵芝, 易小明, 等. 血清CYR61、suPAR、8-OHdG联合检测在AECOPD并发肺动脉高压患者中的临床应用[J]. 国际检验医学杂志, 2023, 44(5): 588-593.

[18] Ushach I, Arrevillaga-Boni G, Heller GN, et al. Meteorin-like/Meteorin-β is a novel immunoregulatory cytokine associated with inflammation[J]. J Immunol, 2018, 201(12): 3669-3676.

[19] El-Ashmawy HM, Selim FO, Hosny TAM, et al. Association of low serum Meteorin like (Metrnl) concentrations with worsening of glucose tolerance, impaired endothelial function and atherosclerosis[J]. Diabetes Res Clin Pract, 2019, 150: 57-63.

[20] 曹红, 张小萌, 许琮. 镍纹蛋白样β对脂多糖诱导心肌细胞损伤的抑制作用及其机制[J]. 山东医药, 2023, 63(23): 1-4.

[21] Chen Z, Li J, Peng H, et al. Meteorin-like/Meteorin-β protects LPS-induced acute lung injury by activating SIRT1-P53-SLC7A11 mediated ferroptosis pathway[J]. Mol Med, 2023, 29(1): 144.

[22] 李小英, 李静, 胡小露. 小儿下呼吸道细菌感染者病原菌构成及耐药性与病情严重程度相关性研究[J]. 山西医药杂志, 2021, 50(4): 535-538.

基金资助

四川省妇幼保健协会科研课题(21FX020)