Sallee Colin J, Hippensteel Joseph A, Miller Kristen R, Oshima Kaori, Pham Andrew T, Richter Robert P, Belperio John, Sierra Yamila L, Schwingshackl Andreas, Mourani Peter M, Schmidt Eric P, Sapru Anil, Maddux Aline B
Department of Pediatrics, Division of Pediatric Critical Care Medicine, David Geffen School of Medicine at University of California Los Angeles and Mattel Children's Hospital, Los Angeles, CA, USA.
Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
J Intensive Care Med. 2024 Mar;39(3):277-287. doi: 10.1177/08850666231200162. Epub 2023 Sep 6.
Sepsis-associated destruction of the pulmonary microvascular endothelial glycocalyx (EGCX) creates a vulnerable endothelial surface, contributing to the development of acute respiratory distress syndrome (ARDS). Constituents of the EGCX shed into circulation, glycosaminoglycans and proteoglycans, may serve as biomarkers of endothelial dysfunction. We sought to define the patterns of plasma EGCX degradation products in children with sepsis-associated pediatric ARDS (PARDS), and test their association with clinical outcomes.
We retrospectively analyzed a prospective cohort (2018-2020) of children (≥1 month to <18 years of age) receiving invasive mechanical ventilation for acute respiratory failure for ≥72 h. Children with and without sepsis-associated PARDS were selected from the parent cohort and compared. Blood was collected at time of enrollment. Plasma glycosaminoglycan disaccharide class (heparan sulfate, chondroitin sulfate, and hyaluronan) and sulfation subtypes (heparan sulfate and chondroitin sulfate) were quantified using liquid chromatography tandem mass spectrometry. Plasma proteoglycans (syndecan-1) were measured through an immunoassay.
Among the 39 mechanically ventilated children (29 with and 10 without sepsis-associated PARDS), sepsis-associated PARDS patients demonstrated higher levels of heparan sulfate (median 639 ng/mL [interquartile range, IQR 421-902] vs 311 [IQR 228-461]) and syndecan-1 (median 146 ng/mL [IQR 32-315] vs 8 [IQR 8-50]), both = 0.01. Heparan sulfate subtype analysis demonstrated greater proportions of -sulfated disaccharide levels among children with sepsis-associated PARDS (0.01). Increasing sulfated disaccharide levels by quartile were associated with severe PARDS (n = 9/29) with the highest quartile including >60% of the severe PARDS patients (test for trend, = 0.04). Higher total heparan sulfate and sulfated disaccharide levels were independently associated with fewer 28-day ventilator-free days in children with sepsis-associated PARDS (all 0.05).
Children with sepsis-associated PARDS exhibited higher plasma levels of heparan sulfate disaccharides and syndecan-1, suggesting that EGCX degradation biomarkers may provide insights into endothelial dysfunction and PARDS pathobiology.
脓毒症相关的肺微血管内皮糖萼（EGCX）破坏会形成脆弱的内皮表面，促使急性呼吸窘迫综合征（ARDS）的发生。脱落进入循环的EGCX成分，即糖胺聚糖和蛋白聚糖，可能作为内皮功能障碍的生物标志物。我们试图确定脓毒症相关儿童急性呼吸窘迫综合征（PARDS）患儿血浆EGCX降解产物的模式，并测试它们与临床结局的关联。
我们回顾性分析了一个前瞻性队列（2018 - 2020年）中因急性呼吸衰竭接受有创机械通气≥72小时的儿童（≥1个月至<18岁）。从母队列中选取患有和未患有脓毒症相关PARDS的儿童并进行比较。在入组时采集血液。使用液相色谱串联质谱法定量血浆糖胺聚糖二糖类别（硫酸乙酰肝素、硫酸软骨素和透明质酸）和硫酸化亚型（硫酸乙酰肝素和硫酸软骨素）。通过免疫测定法测量血浆蛋白聚糖（Syndecan - 1）。
在39名接受机械通气的儿童中（29名患有脓毒症相关PARDS，10名未患），脓毒症相关PARDS患者的硫酸乙酰肝素水平更高（中位数639 ng/mL [四分位间距，IQR 421 - 902] 对比311 [IQR 228 - 461]）以及Syndecan - 1水平更高（中位数146 ng/mL [IQR 32 - 315] 对比8 [IQR 8 - 50]），两者均P = 0.01。硫酸乙酰肝素亚型分析显示，脓毒症相关PARDS患儿中 - 硫酸化二糖水平的比例更高（P = 0.01）。按四分位数增加硫酸化二糖水平与重度PARDS（n = 9/29）相关，最高四分位数组包括>60%的重度PARDS患者（趋势检验，P = 0.04）。在脓毒症相关PARDS患儿中，较高的总硫酸乙酰肝素和硫酸化二糖水平与28天无呼吸机天数减少独立相关（均P < 0.05）。
脓毒症相关PARDS患儿的血浆硫酸乙酰肝素二糖和Syndecan - 1水平较高，表明EGCX降解生物标志物可能为内皮功能障碍和PARDS病理生物学提供见解。
