Channing Division of Network Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA, 02115, USA.
Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA.
Respir Res. 2018 Jun 26;19(1):128. doi: 10.1186/s12931-018-0828-6.
Circulating microRNAs have shown promise as non-invasive biomarkers and predictors of disease activity. Prior asthma studies using clinical, biochemical and genomic data have not shown excellent prediction of exacerbation. We hypothesized that a panel of circulating microRNAs in a pediatric asthma cohort combined with an exacerbation clinical score might predict exacerbation better than the latter alone.
Serum samples from 153 children at randomization in the Childhood Asthma Management Program were profiled for 754 microRNAs. Data dichotomized for asthma exacerbation one year after randomization to inhaled corticosteroid treatment were used for binary logistic regression with miRNA expressions and exacerbation clinical score.
12 of 125 well-detected circulating microRNAs had significant odd ratios for exacerbation with miR-206 being most significant. Each doubling of expression of the 12 microRNA corresponded to a 25-67% increase in exacerbation risk. Stepwise logistic regression yielded a 3-microRNA model (miR-146b, miR-206 and miR-720) that, combined with the exacerbation clinical score, had excellent predictive power with a 0.81 AUROC. These 3 microRNAs were involved in NF-kβ and GSK3/AKT pathways.
This combined circulating microRNA-clinical score model predicted exacerbation in asthmatic subjects on inhaled corticosteroids better than each constituent feature alone.
ClinicalTrials.gov Identifier: NCT00000575 .
循环 microRNA 作为非侵入性生物标志物和疾病活动预测因子的潜力已得到证实。先前使用临床、生化和基因组数据的哮喘研究并未显示出对加重的优异预测。我们假设，儿科哮喘队列中循环 microRNA 谱与加重临床评分相结合，可能比后者单独预测加重更好。
随机分组的 153 名儿童在儿童哮喘管理计划中的血清样本进行了 754 个 microRNA 的分析。将随机分组后一年因吸入皮质类固醇治疗而加重的哮喘患者的临床评分数据进行二项逻辑回归分析，以 microRNA 表达和加重临床评分。
125 个检测良好的循环 microRNA 中有 12 个与加重有显著的比值比，miR-206 最为显著。12 个 microRNA 表达的每一倍增加，与加重风险增加 25%-67%相对应。逐步逻辑回归产生了一个 3-microRNA 模型（miR-146b、miR-206 和 miR-720），与加重临床评分相结合，具有优异的预测能力，AUROC 为 0.81。这 3 个 microRNA 参与了 NF-kβ 和 GSK3/AKT 通路。
与单独的特征相比，这种循环 microRNA-临床评分联合模型可以更好地预测吸入皮质类固醇治疗的哮喘患者的加重情况。
ClinicalTrials.gov 标识符：NCT00000575 。
