Department of Neonatology and Pediatric Critical Care Medicine, University of Bonn , Bonn , Germany.
Department of Obstetrics and Prenatal Medicine, University of Bonn , Bonn , Germany.
Am J Physiol Lung Cell Mol Physiol. 2019 Jun 1;316(6):L1061-L1069. doi: 10.1152/ajplung.00359.2018. Epub 2019 Mar 6.
Pulmonary hypertension (PH) and lung hypoplasia are major contributors to morbidity and mortality in newborns with congenital diaphragmatic hernia (CDH). The soluble receptor for advanced glycation end products (sRAGE) is a marker of endothelial function and might be associated with disease severity in CDH newborns. In a cohort of 30 CDH newborns and 20 healthy control newborns, sRAGE concentration was measured at birth and at 6 h, 12 h, 24 h, 48 h, and 7-10 days. In healthy newborns, sRAGE was significantly higher at birth and at 48 h compared with CDH newborns (both < 0.001). Among CDH newborns, sRAGE was significantly lower at birth ( = 0.033) and at 7-10 days ( = 0.035) in patients receiving extracorporeal membrane oxygenation (ECMO) compared with patients not receiving ECMO. In contrast, CDH newborns receiving ECMO had significantly higher values at 6 h ( = 0.001), 12 h ( = 0.004), and 48 h (0.032). Additionally, sRAGE correlated significantly with PH severity, intensity and duration of mechanical ventilation, and prenatally assessed markers of CDH severity (lung size, liver herniation). The probability to receive ECMO therapy was five times higher in CDH newborns with sRAGE concentrations below the calculated cutoff of 650 pg/ml at birth ( = 0.002) and nine times higher in CDH newborns with sRAGE concentrations above the cutoff of 3,500 pg/ml at 6 h ( = 0.001). These findings suggest a potential involvement of sRAGE in the pathophysiology of CDH and may act as a therapeutic target in future treatment approaches.
肺高血压（PH）和肺发育不全是先天性膈疝（CDH）新生儿发病率和死亡率的主要原因。晚期糖基化终产物可溶性受体（sRAGE）是血管内皮功能的标志物，可能与 CDH 新生儿的疾病严重程度有关。在 30 例 CDH 新生儿和 20 例健康对照组新生儿的队列中，分别在出生时以及出生后 6 h、12 h、24 h、48 h 和 7-10 d 测量 sRAGE 浓度。在健康新生儿中，sRAGE 在出生时和 48 h 时均显著高于 CDH 新生儿（均<0.001）。在 CDH 新生儿中，接受体外膜氧合（ECMO）治疗的患儿 sRAGE 在出生时（=0.033）和 7-10 d 时（=0.035）显著低于未接受 ECMO 治疗的患儿。相反，接受 ECMO 治疗的 CDH 新生儿在 6 h（=0.001）、12 h（=0.004）和 48 h（0.032）时的 sRAGE 值显著更高。此外，sRAGE 与 PH 严重程度、机械通气强度和持续时间以及产前评估的 CDH 严重程度标志物（肺大小、肝疝入）显著相关。在出生时 sRAGE 浓度低于计算出的 650 pg/ml 截断值的 CDH 新生儿中，接受 ECMO 治疗的概率增加 5 倍（=0.002），而在出生后 6 h 时 sRAGE 浓度高于 3500 pg/ml 截断值的 CDH 新生儿中，接受 ECMO 治疗的概率增加 9 倍（=0.001）。这些发现表明 sRAGE 可能参与了 CDH 的病理生理过程，并可能成为未来治疗方法的一个治疗靶点。
