儿童难治性肺炎支原体肺炎膜联蛋白A1与疾病严重程度及塑型性支气管炎的关系

Association of ANXA1 with disease severity and plastic bronchitis in children with refractory Mycoplasma pneumoniae pneumonia

摘要

目的 探究儿童难治性肺炎支原体肺炎(RMPP)膜联蛋白A1(ANXA1)的变化与疾病严重程度的关系及对塑型性支气管炎的预测。方法 选取2022年3月至2024年3月间于我院进行治疗的159名RMPP患儿作为研究对象,另选同期于我院体检的72名健康儿童作为对照组,根据患儿的临床表现将患儿分为轻症组(n=94),重症组(n=65),后续根据RMPP患儿是否合并塑型性支气管炎(PB)将RMPP患儿分为PB组(n=55)和未患PB组(n=104)。采用多元线性回归分析ANXA1水平与免疫指标的关系;构建广义线性混合模型(GLMMs)分析ANXA1水平与RMPP严重程度的相关性。采用独立相关性分析探究ANXA1水平与PB的独立相关性;相关性亚组分析探究不同条件下ANXA1水平与PB的关系;限制性立方样条(RCS)模型分析ANXA1水平与PB的剂量-反应关系。结果 ANXA1水平与T淋巴细胞亚群(CD3⁺、CD4⁺、CD8⁺、CD4⁺/CD8⁺)等免疫指标之间存在相关性(β分别为0.402、0.533、0.587、0.439,P＜0.05);GLMMs模型显示以ANXA1水平＜264μg/L为参照,ANXA1水平在264μg/L~352μg/L及＞352μg/L时均会加重疾病程度(OR值及其95%CI分别为2.240(1.938~2.839)、3.424(2.801~3.987))。ANXA1水平为PB的独立危险因素,与ANXA1最低的五分位组数(Q₁)比较,随着ANXA1水平的提高(Q₂~Q₅组),OR及其95%CI分别为1.745(1.721~1.770)、1.687(1.634~1.728)、1.688(1.629~1.748)、1.742(1.705~1.793);在不同混杂因素下,ANXA1水平与PB风险的相关性稳定存在,且亚组间不存在相互作用(P_交互＞0.05);RCS模型分析显示,ANXA1水平与轻症RMPP患者和重症RMPP患者PB发病呈现非线性增高趋势(非线性检验均P＜0.001)。结论 研究发现,ANXA1水平与儿童难治性肺炎支原体肺炎疾病严重程度呈正相关关系,ANXA1水平与塑型性支气管炎发病呈现正相关关系,随着ANXA1水平的提高,出现塑型性支气管炎的概率越大。

Abstract

Objective To explore the relationship between Annexin A1 (ANXA1) levels and the severity of refractory Mycoplasma pneumoniae pneumonia (RMPP),and to evaluate its predictive value for plastic bronchitis. Methods A total of 159 children with RMPP who were treated in our hospital from March 2022 to March 2024 were selected as the research subjects,and 72 healthy children who underwent physical examination in our hospital during the same period were selected as the control group.According to the clinical manifestations,RMPP patients were divided into a mild group (n=94) and a severe group (n=65),while healthy children served as the control group (n=72).Subsequently,according to whether the children with RMPP were complicated with plastic bronchitis (PB),they were divided into a PB group (n=55) and a non-PB group (n=104).Multivariate linear regression analysis was conducted to explore the relationship between ANXA1 levels and immune indicators;generalized linear mixed models (GLMMs) were used to analyze the correlation between ANXA1 levels and the severity of RMPP.Independent correlation analysis was performed to investigate the independent association between ANXA1 levels and PB;subgroup correlation analysis was carried out to explore the relationship between ANXA1 levels and PB under different conditions;and a restricted cubic spline (RCS) model was applied to analyze the dose-response relationship between ANXA1 levels and PB. Results The level of ANXA1 was correlated with T lymphocyte subsets (CD3⁺,CD4⁺,CD8⁺,CD4⁺/CD8⁺) and other immune indicators (β=0.402,0.533,0.587,0.439,P＜0.05).GLMMs model showed that ANXA1 level was positively correlated with disease severity (OR=2.240,95%CI:1.938-2.839;OR=3.424,95%CI:2.801-3.987,respectively).The level of ANXA1 was an independent risk factor for PB.Compared with the lowest quintile (Q1),higher ANXA1 quintiles (Q2-Q5) were associated with an increased risk of PB (ORs ranged from 1.687 to 1.745,respectively P＜0.001).Under different confounding factors,the correlation between ANXA1 level and PB risk remained stable,and there was no interaction between the subgroups (P_interaction＞0.05).RCS model analysis showed that the level of ANXA1 showed a nonlinear increase trend with the incidence of PB in mild RMPP patients and severe RMPP patients (nonlinear test P＜0.001). Conclusion This study found that ANXA1 levels were positively associated with disease severity in children with RMPP and with the occurrence of plastic bronchitis.Higher ANXA1 levels were associated with an increased probability of PB.

关键词

儿童 / 支原体肺炎 / 难治性肺炎 / 塑型性支气管炎 / 膜联蛋白A1 / 病情程度

Key words

child / mycoplasma pneumoniae pneumonia / refractory pneumonia / plastic bronchitis / AnnexinA1 / disease severity

参考文献

[1] Song Z, Jia G, Luo G, et al. Global research trends of Mycoplasma pneumoniae pneumonia in children:a bibliometric analysis[J]. Front Pediatr, 2023, 11: 1306234.

[2] Tong L, Huang S, Zheng C, et al. Refractory mycoplasma pneumoniae pneumonia in children:early recognition and management[J]. J Clin Med, 2022, 11(10): 2824.

[3] Patel N, Patel M, Inja R, et al. Plastic bronchitis in adult and pediatric patients:a review of its presentation,diagnosis,and treatment[J]. Mo Med, 2021, 118(4): 363-373.

[4] Yamasaki K, Morimoto T, Hashimoto K, et al. Plastic bronchitis caused by Haemophilus influenzae[J]. Respirol Case Rep, 2023, 11(12): e1248.

[5] Yang L, Zhang Y, Shen C, et al. Clinical features and risk factors of plastic bronchitis caused by Mycoplasma pneumoniae pneumonia in children[J]. BMC Pulm Med, 2023, 23(1): 468.

[6] Zhang J, Wang H, Liu J, et al. ANXA1 is identified as a key gene associated with high risk and T cell infiltration in primary sclerosing cholangitis[J]. Hum Genomics, 2023, 17(1): 86.

[7] Gu M, Han X, Liu X, et al. Predictive value of annenxin A1 for disease severity and prognosis in patients with community-acquired pneumonia[J]. Diagnostics (Basel), 2023, 13(3): 396.

[8] 佟立新, 孙同英, 徐莎, 等. 血清SAA、HC-gp39及SF检测在小儿难治性肺炎支原体肺炎预后评估中的应用价值研究[J]. 解放军医药杂志, 2021, 33(9): 69-73.

[9] 中华中医药学会儿童肺炎协作创新共同体, 中国中药协会儿童健康与药物研究专业委员会, 《中国实用儿科杂志》编辑委员会, 等. 儿童肺炎支原体肺炎中西医结合诊治专家共识(2023年)[J]. 中国实用儿科杂志, 2024, 39(3): 161-167,222.

[10] 王倩云, 王海立, 邵贤丽, 等. 难治性肺炎支原体肺炎患儿需行支气管镜辅助治疗风险预测模型的构建与验证[J]. 中国妇幼健康研究, 2023, 34(5): 82-88.

[11] Jiang Z, Li S, Zhu C, et al. Mycoplasma pneumoniae Infections:pathogenesis and vaccine development[J]. Pathogens, 2021, 10(2): 119.

[12] Fan F, Lv J, Yang Q, et al. Clinical characteristics and serum inflammatory markers of community-acquired mycoplasma pneumonia in children[J]. Clin Respir J, 2023, 17(7): 607-617.

[13] Ding G, Zhang X, Vinturache A, et al. Challenges in the treatment of pediatric Mycoplasma pneumoniae pneumonia[J]. Eur J Pediatr, 2024, 183(7): 3001-3011.

[14] Zhang H, Yang J, Zhao W, et al. Clinical features and risk factors of plastic bronchitis caused by refractory mycoplasma pneumoniae pneumonia in children:a practical nomogram prediction model[J]. Eur J Pediatr, 2023, 182(3): 1239-1249.

[15] 孙源, 赵立涵, 曾玮, 等. 重症肺炎患者血清ANXA1、TIM-4表达水平及临床意义[J]. 临床肺科杂志, 2023, 28(11): 1635-1639.

[16] Zheng Y, Jiang H, Yang N, et al. Glioma-derived ANXA1 suppresses the immune response to TLR3 ligands by promoting an anti-inflammatory tumor microenvironment[J]. Cell Mol Immunol, 2024, 21(1): 47-59.

[17] Zhang D, Wang W, Zhou H, et al. ANXA1:an important independent prognostic factor and molecular target in glioma[J]. Front Genet, 2022, 13: 851505.

[18] Ansari J, Senchenkova E Y, Vital S A, et al. Targeting the AnxA1/Fpr2/ALX pathway regulates neutrophil function,promoting thromboinflammation resolution in sickle cell disease[J]. Blood, 2021, 137(11): 1538-1549.

[19] 陈少英, 晏平, 陈贵斌, 等. 西乐葆对重症肺炎小鼠ANXA/FPR2通路及炎症反应的影响[J]. 中国免疫学杂志, 2022, 38(21): 2578-2582.

[20] 吴海明, 陈曦, 杨云燕, 等. 呼吸道合胞病毒感染致毛细支气管炎患儿血清ANXA1、NGAL水平及其临床意义[J]. 国际检验医学杂志, 2023, 44(17): 2173-2176.