OBJECTIVES: 

Soluble receptor for advanced glycation end products is a known plasma marker of alveolar epithelial injury. However, RAGE is also expressed on cell types beyond the lung, and its activation leads to up-regulation of pro-inflammatory mediators. We sought to examine the relationship between plasma soluble receptor for advanced glycation end products and primary pulmonary dysfunction, extrapulmonary organ dysfunction, and mortality in pediatric acute respiratory distress syndrome patients at two early time points following acute respiratory distress syndrome diagnosis and compare these results to plasma surfactant protein-D, a marker of pure alveolar epithelial injury.

DESIGN: 

Prospective observational study.

SETTING: 

Five academic PICUs.

PATIENTS: 

Two hundred fifty-eight pediatric patients 30 days to 18 years old meeting Berlin Criteria for acute respiratory distress syndrome.

INTERVENTIONS: 

None.

MEASUREMENTS AND MAIN RESULTS: 

Plasma was collected for soluble receptor for advanced glycation end products and surfactant protein-D measurements within 24 hours (day 1) and 48 to 72 hours (day 3) after acute respiratory distress syndrome diagnosis. Similar to surfactant protein-D, plasma soluble receptor for advanced glycation end products was associated with a higher oxygenation index (p < 0.01) and worse lung injury score (p < 0.001) at the time of acute respiratory distress syndrome diagnosis. However, unlike surfactant protein-D, plasma soluble receptor for advanced glycation end products was associated with worse extrapulmonary Pediatric Logistic Organ Dysfunction score during ICU stay (day 3; p < 0.01) and positively correlated with plasma levels of interleukin-6 (p < 0.01), tumor necrosis factor-α (p < 0.01), and angiopoietin-2 (p < 0.01). Among children with indirect lung injury, plasma soluble receptor for advanced glycation end products was associated with mortality independent of age, sex, race, cancer/bone marrow transplant, and Pediatric Risk of Mortality score (day 3; odds ratio, 3.14; 95% CI, 1.46–6.75; p < 0.01).

CONCLUSIONS: 

Unlike surfactant protein-D, which is primarily localized to the alveolar epithelium plasma soluble receptor for advanced glycation end products is systemically expressed and correlates with markers of inflammation, extrapulmonary multiple organ dysfunction, and death in pediatric acute respiratory distress syndrome with indirect lung injury. This suggests that unlike surfactant protein-D, soluble receptor for advanced glycation end products is a multifaceted marker of alveolar injury and increased inflammation and that receptor for advanced glycation end products activation may contribute to the pathogenesis of multiple organ failure among children with indirect acute respiratory distress syndrome.

中文翻译：

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肺泡上皮之外：晚期糖化终产物的血浆可溶性受体与急性呼吸窘迫综合征儿童的氧合损伤、死亡率和肺外器官衰竭相关

目标： 

晚期糖基化终产物的可溶性受体是肺泡上皮损伤的已知血浆标志物。然而，RAGE 也在肺以外的细胞类型上表达，其激活导致促炎介质的上调。我们试图在急性呼吸窘迫综合征诊断后的两个早期时间点检查晚期糖基化终末产物的血浆可溶性受体与原发性肺功能障碍、肺外器官功能障碍和死亡率之间的关系，并将这些结果与血浆进行比较表面活性蛋白-D，纯肺泡上皮损伤的标志物。

设计： 

前瞻性观察研究。

环境： 

五个学术 PICU。

患者： 

258 名 30 天至 18 岁的儿科患者符合急性呼吸窘迫综合征柏林标准。

干预措施： 

没有任何。

测量和主要结果： 

急性呼吸窘迫综合征诊断后 24 小时（第 1 天）和 48 至 72 小时（第 3 天）内收集血浆进行晚期糖基化终产物的可溶性受体和表面活性剂蛋白-D测量。与表面活性剂蛋白-D类似，晚期糖基化终末产物的血浆可溶性受体与急性呼吸窘迫综合征诊断时较高的氧合指数 ( p < 0.01) 和较差的肺损伤评分 ( p < 0.001)相关。然而，与表面活性剂蛋白-D不同，晚期糖基化终末产物的血浆可溶性受体与 ICU 住院期间（第 3 天； p < 0.01 ）较差的肺外儿科逻辑器官功能障碍评分相关，并且与血浆白细胞介素6 水平呈正相关（p < 0.01）、肿瘤坏死因子-α（p < 0.01）和血管生成素-2（p < 0.01）。在间接肺损伤的儿童中，晚期糖基化终末产物的血浆可溶性受体与死亡率相关，与年龄、性别、种族、癌症/骨髓移植和儿科死亡风险评分无关（第 3 天；比值比，3.14；95%） CI，1.46–6.75；p < 0.01）。

结论： 

与表面活性剂蛋白-D不同，表面活性剂蛋白-D 主要定位于晚期糖基化终产物的肺泡上皮血浆可溶性受体，它是全身表达的，并且与炎症标志物、肺外多器官功能障碍以及儿童急性呼吸窘迫综合征伴间接肺损伤的死亡相关。这表明，与表面活性剂蛋白-D不同，晚期糖基化终末产物的可溶性受体是肺泡损伤和炎症增加的多方面标志物，并且晚期糖基化终末产物的受体激活可能导致间接急性呼吸道儿童多器官衰竭的发病机制。苦恼综合症。