PDF(Pubmed)
Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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 p = 0.01. Heparan sulfate subtype analysis demonstrated greater proportions of N-sulfated disaccharide levels among children with sepsis-associated PARDS (p = 0.01). Increasing N-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, p = 0.04). Higher total heparan sulfate and N-sulfated disaccharide levels were independently associated with fewer 28-day ventilator-free days in children with sepsis-associated PARDS (all p < 0.05).
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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 p = 0.01. Heparan sulfate subtype analysis demonstrated greater proportions of N-sulfated disaccharide levels among children with sepsis-associated PARDS (p = 0.01). Increasing N-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, p = 0.04). Higher total heparan sulfate and N-sulfated disaccharide levels were independently associated with fewer 28-day ventilator-free days in children with sepsis-associated PARDS (all p < 0.05).
CONCLUSIONS: 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.
摘要：
背景：与脓毒症相关的肺微血管内皮糖萼（EGCX）的破坏会产生脆弱的内皮表面，导致急性呼吸窘迫综合征（ARDS）的发展。EGCX的成分流入流通，糖胺聚糖和蛋白聚糖，可以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小儿ARDS（PARDS）患儿血浆EGCX降解产物的模式，并测试它们与临床结果的关联。
方法：我们回顾性分析了一项前瞻性队列（2018-2020年）接受有创机械通气治疗急性呼吸衰竭≥72h的儿童（≥1个月至<18岁）。从父母队列中选择有和无败血症相关PARDS的儿童并进行比较。在登记时收集血液。血浆糖胺聚糖二糖类(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）使用液相色谱串联质谱法进行定量。通过免疫测定法测量血浆蛋白聚糖（syndecan-1）。
结果：在39名机械通气儿童（29名和10名无败血症相关PARDS）中，脓毒症相关PARDS患者的硫酸乙酰肝素水平较高（中位数639ng/mL[四分位距，IQR421-902]vs311[IQR228-461]）和syndecan-1（中位数146ng/mL[IQR32-315]vs8[IQR8-50]），两者p=0.01。硫酸乙酰肝素亚型分析显示，脓毒症相关PARDS患儿中N-硫酸化二糖水平的比例更高（p=0.01）。通过四分位数增加N-硫酸化二糖水平与严重PARDS（n=9/29）相关，四分位数最高，包括>60％的严重PARDS患者（趋势测试，p=0.04)。在脓毒症相关的PARDS患儿中，较高的总硫酸乙酰肝素和N-硫酸二糖水平与较少的28天无呼吸机天数独立相关（均p<0.05）。
结论：脓毒症相关PARDS患儿血浆中硫酸乙酰肝素二糖和syndecan-1水平较高，提示EGCX降解生物标志物可提供对内皮功能障碍和PARDS病理生物学的认识。
方法：我们回顾性分析了一项前瞻性队列（2018-2020年）接受有创机械通气治疗急性呼吸衰竭≥72h的儿童（≥1个月至<18岁）。从父母队列中选择有和无败血症相关PARDS的儿童并进行比较。在登记时收集血液。血浆糖胺聚糖二糖类(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）使用液相色谱串联质谱法进行定量。通过免疫测定法测量血浆蛋白聚糖（syndecan-1）。
结果：在39名机械通气儿童（29名和10名无败血症相关PARDS）中，脓毒症相关PARDS患者的硫酸乙酰肝素水平较高（中位数639ng/mL[四分位距，IQR421-902]vs311[IQR228-461]）和syndecan-1（中位数146ng/mL[IQR32-315]vs8[IQR8-50]），两者p=0.01。硫酸乙酰肝素亚型分析显示，脓毒症相关PARDS患儿中N-硫酸化二糖水平的比例更高（p=0.01）。通过四分位数增加N-硫酸化二糖水平与严重PARDS（n=9/29）相关，四分位数最高，包括>60％的严重PARDS患者（趋势测试，p=0.04)。在脓毒症相关的PARDS患儿中，较高的总硫酸乙酰肝素和N-硫酸二糖水平与较少的28天无呼吸机天数独立相关（均p<0.05）。
结论：脓毒症相关PARDS患儿血浆中硫酸乙酰肝素二糖和syndecan-1水平较高，提示EGCX降解生物标志物可提供对内皮功能障碍和PARDS病理生物学的认识。
