循环lnc-NEAT1/miR-124轴与哮喘患儿急性发作风险、疾病严重程度和炎症的关联分析

Correlation of circulating lnc-NEAT1/miR-124 axis expression with acute exacerbation risk, disease severity and inflammation in childhood asthma patients

为评估长链非编码RNA核富集转录体1(long non-coding RNA nuclear enriched abundant transcript 1, lnc-NEAT1)/miR-124轴对儿童哮喘急性发作风险的预测作用,并探讨其与肺部通气功能、疾病严重程度及炎症的关联,连续纳入急性发作期哮喘患儿95例、缓解期哮喘患儿95例及健康对照儿童90例。哮喘患儿和健康儿童均进行肺部通气功能检测,并采集其外周血以检测血浆中lnc-NEAT1和miR-124的表达水平及炎性因子(TNF-α、IL-1β、IL-6和IL-17)水平,评估急性发作期哮喘患儿的疾病严重程度。结果显示,lnc-NEAT1/miR-124轴在急性发作期哮喘患儿中的表达量较缓解期哮喘患儿和健康儿童高(P<0.001)。受试者工作特征(receiver operating characteristic, ROC)曲线表明,lnc-NEAT1/miR-124轴可很好地区分急性发作期哮喘患儿与健康儿童[AUC 0.894,95%可信区间(confidence interval,CI)0.850~0.938]、缓解期哮喘患儿(AUC 0.830,95%CI 0.774~0.886),且能区分缓解期哮喘患儿与健康儿童(AUC 0.642,95%CI 0.562~0.722)。在急性发作期哮喘患儿中,lnc-NEAT1/miR-124轴表达量与第1秒用力呼气容积(forced expiratory volume in 1 second,FEV1)/用力肺活量(forced vital capacity,FVC)和FEV1%预计值均呈负相关(P<0.001),与TNF-α、IL-1β、IL-6和IL-17呈正相关(P<0.05),与急性发作期哮喘严重程度呈正相关(P<0.001)。在缓解期哮喘患儿和健康儿童中,lnc-NEAT1/miR-124轴表达量与肺通气功能无关联,而与TNF-α、IL-1β、IL-6和IL-17呈正相关(P<0.05)。该研究表明,循环lnc-NEAT1/miR-124轴在哮喘患儿中呈高表达,可预测儿童哮喘急性发作的风险,且其高表达与急性发作期哮喘患儿较差的肺通气功能、疾病严重程度和炎症水平相关。

The aim of this study is to investigate the predictive value of long non-coding RNA nuclear enriched abundant transcript 1(lnc-NEAT1)/miR-124 axis for childhood asthma with acute exacerbation, and explore their correlation with pulmonary ventilation function, disease severity and inflammatory cytokines.Ninety-five children with acute exacerbation of asthma, 95 children with remission stage of asthma and 90 healthy controls were consecutively enrolled in this study. All patients and healthy controls were performed test for pulmonary ventilation function and their plasma samples were collected. lnc-NEAT1 and miR-124 expressions were measured, as well as the inflammatory cytokines including TNF-α, IL-1β, IL-6 and IL-17. Besides, disease severity in children with acute exacerbation of asthma was assessed. The results showed that lnc-NEAT1/miR-124 axis expression was elevated in children with acute exacerbation of asthma compared to children with remission stage of asthma or healthy controls(P<0.001). In addition, receiver operating characteristic(ROC) curve showed that lnc-NEAT1/miR124 axis well distinguished children with acute exacerbation of asthma from healthy controls [AUC 0.894, 95% confidence interval(CI) 0.850-0.938] and children with remission stage of asthma(AUC 0.830, 95% CI 0.774-0.886), and also could distinguish children with remission stage of asthma from healthy controls(AUC 0.642, 95% CI 0.562-0.722). In children with acute exacerbation of asthma, lnc-NEAT1/miR-124 axis expression negatively correlated with forced expiratory volume in 1 second(FEV1)/forced vital capacity(FVC) and FEV1% values(P<0.001), but positively correlated with TNF-α,IL-1β,IL-6 and IL-17 levels as well as the disease severity(P<0.05). In children with remission stage of asthma and healthy controls, no correlation of lnc-NEAT1/miR-124 axis expression with pulmonary ventilation function was found, while lnc-NEAT1/miR-124 axis expression was positively correlated with TNF-α, IL-1β, IL-6 and IL-17 levels(P<0.05). In conclusion, circulating lnc-NEAT1/miR-124 axis is overexpressed in asthma children and could predict the increased acute exacerbation of childhood asthma risk. Moreover, its high expression correlates with worse pulmonary ventilation function, disease severity and inflammation level in children with acute exacerbation of asthma.