Aoki Joni A, Denorme Frederik, Cody Mark J, Perry David P, Rustad John L, Brown Samuel M, Goldstein Stephanie A, Middleton Elizabeth A, Yost Christian C, Harris Estelle S
University of Utah School of Medicine, Salt Lake City, UT, USA.
Department of Internal Medicine, University of Utah, 30 North Mario Capecchi Dr., 2nd Floor North, Salt Lake City, UT, 84112, USA.
J Inflamm (Lond). 2025 Jun 13;22(1):22. doi: 10.1186/s12950-025-00448-8.
Although studies have evaluated the presence of cell-free DNA and neutrophil extracellular traps (NETs) in acute respiratory distress syndrome (ARDS), the kinetics of NET formation during the early ICU admission and whether plasma NET markers correlate with clinical outcomes in patients with moderate-to-severe hypoxemia remain unknown. We sought to determine whether serial plasma NET marker levels in study participants collected over 48 h post enrollment predict disease severity and mortality in non-COVID-19 ARDS patients.
We obtained previously collected plasma samples (trial enrollment, 24 h, 48 h) from 200 randomly selected ARDS participants in the completed Reevaluation of Systemic Early Neuromuscular Blockade (ROSE) Trial, as well as from 20 healthy control donors. We determined plasma levels of surrogate biomarkers for NETs using a cell-free DNA fluorescence assay and a plasma myeloperoxidase (MPO)-DNA complex ELISA. We correlated these surrogate biomarker levels with clinical outcomes from the ROSE trial study participants.
ROSE plasma samples demonstrated significantly higher NET levels compared to healthy donor controls. Individual study participant NET levels did not change over the forty-eight hours after trial enrollment. Higher levels of both surrogate markers correlated with fewer ventilator-free days, but only cell free-DNA correlated with mortality and higher illness severity scores.
Surrogate markers for plasma NET levels measured in patients with moderate or severe ARDS correlate directly with adverse clinical outcomes and may serve as biomarkers for predicting severe disease. Further studies of surrogate biomarkers for NET formation in moderate-to-severe ARDS are warranted.
尽管已有研究评估了急性呼吸窘迫综合征（ARDS）中游离DNA和中性粒细胞胞外诱捕网（NETs）的存在情况，但在入住重症监护病房（ICU）早期NET形成的动力学，以及中度至重度低氧血症患者血浆NET标志物是否与临床结局相关仍不清楚。我们试图确定在入组后48小时内收集的研究参与者的系列血浆NET标志物水平是否能预测非COVID-19 ARDS患者的疾病严重程度和死亡率。
我们从已完成的系统性早期神经肌肉阻滞再评估（ROSE）试验中随机选择的200名ARDS参与者以及20名健康对照供体中获取了先前收集的血浆样本（试验入组时、24小时、48小时）。我们使用游离DNA荧光测定法和血浆髓过氧化物酶（MPO）-DNA复合物酶联免疫吸附测定法（ELISA）测定了NETs替代生物标志物的血浆水平。我们将这些替代生物标志物水平与ROSE试验研究参与者的临床结局进行了关联。
与健康供体对照相比，ROSE血浆样本显示出明显更高的NET水平。在试验入组后的48小时内，个体研究参与者的NET水平没有变化。两种替代标志物水平越高，无呼吸机天数越少，但只有游离DNA与死亡率和更高的疾病严重程度评分相关。
在中度或重度ARDS患者中测量的血浆NET水平替代标志物与不良临床结局直接相关，可能作为预测严重疾病的生物标志物。有必要对中度至重度ARDS中NET形成的替代生物标志物进行进一步研究。
