Division of Pediatric Cardiology, Department of Pediatrics, Johns Hopkins University, Baltimore, MD.
Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD.
Chest. 2021 Jul;160(1):297-306. doi: 10.1016/j.chest.2021.01.085. Epub 2021 Feb 18.
Pediatric pulmonary hypertension is a severe disease defined by sustained elevation of pulmonary artery pressures and pulmonary vascular resistance (PVR). Noninvasive diagnostic and prognostic markers that are more pulmonary vascular specific have been elusive because of disease heterogeneity and patient growth.
Is soluble suppressor of tumorigenicity (ST2) associated with pulmonary hemodynamic and functional changes in pediatric pulmonary hypertension? Does ST2 improve mortality risk models in pediatric pulmonary hypertension?
Two pediatric cohorts (age < 21 years) were assayed for ST2 and N-terminal prohormone B-natriuretic peptide: a cross-sectional cohort from the National Heart Lung and Blood Institute-funded National Biological Sample and Data Repository for PAH (PAHB) (N = 182), and a second longitudinal cohort from Children's Hospital of Colorado (N = 61). Adjusted linear regression was used for association with clinical variables. Clinical mortality models (the Registry to Evaluate Early and Long-Term PAH Disease Management [REVEAL] score) with and without ST2 were used to predict worsening outcomes and compared. Pulmonary artery endothelial and smooth muscle cell ST2 expression and secretion were assayed in vitro.
In an adjusted (age and sex) analysis in the PAHB, ST2 was significantly associated with shorter 6-min walk distance (P = .03) and increased PVR index (P = .02). In adjusted longitudinal regression in the Children's Hospital of Colorado cohort, ST2 was significantly associated with higher PVR index (P < .001), shorter 6-min walk distance (P = .01), and higher mean pulmonary artery pressure (P < .001). Although the REVEAL Risk Score Calculator 2.0 was predictive of clinical worsening in the PAHB (hazard ratio, 1.88), addition of ST2 significantly improved the model (hazard ratio, 2.05). In cell culture, ST2 was produced and secreted predominately by endothelial cells as opposed to smooth muscle cells (P < .0001).
In two pediatric PAH cohorts, elevated ST2 was associated with unfavorable pulmonary hemodynamics and functional measures, clinical worsening, and significantly improved prediction of clinical worsening. Pulmonary artery endothelial cellular expression of ST2 suggests that ST2 is a more pulmonary vascular-specific marker for pulmonary hypertension.
小儿肺动脉高压是一种严重的疾病，其定义为肺动脉压力和肺血管阻力（PVR）持续升高。由于疾病异质性和患者生长，缺乏更具肺血管特异性的非侵入性诊断和预后标志物。
可溶性肿瘤抑制物（ST2）是否与小儿肺动脉高压的肺血流动力学和功能变化相关？ST2 是否能改善小儿肺动脉高压的死亡率风险模型？
对来自国家心肺血液研究所资助的肺动脉高压国家生物样本和数据资源库（PAHB）的横断面队列（N=182）和科罗拉多儿童医院的纵向队列（N=61）进行 ST2 和 N 末端脑钠肽前体（NT-proBNP）检测。采用调整后的线性回归分析与临床变量的关系。使用包含和不包含 ST2 的登记以评估早期和长期肺动脉高压疾病管理（REVEAL）评分的临床死亡率模型来预测不良结局，并进行比较。在体外检测肺动脉内皮和平滑肌细胞 ST2 的表达和分泌。
在 PAHB 的调整后（年龄和性别）分析中，ST2 与 6 分钟步行距离缩短（P=0.03）和 PVR 指数增加（P=0.02）显著相关。在科罗拉多儿童医院的纵向调整回归中，ST2 与更高的 PVR 指数（P<0.001）、更短的 6 分钟步行距离（P=0.01）和更高的平均肺动脉压（P<0.001）显著相关。尽管 REVEAL 风险评分计算器 2.0 可预测 PAHB 中的临床恶化（危险比 1.88），但添加 ST2 可显著改善该模型（危险比 2.05）。在细胞培养中，ST2 主要由内皮细胞而不是平滑肌细胞产生和分泌（P<0.0001）。
在两个儿科 PAH 队列中，升高的 ST2 与不利的肺血流动力学和功能指标、临床恶化以及临床恶化的预测显著改善相关。肺动脉内皮细胞 ST2 的表达表明 ST2 是肺动脉高压更具肺血管特异性的标志物。
