Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
Division of Critical Care Medicine, Children's Healthcare of Atlanta at Egleston, 1405 Clifton Road NE, Atlanta, GA, 30322, USA.
Sci Rep. 2020 Nov 4;10(1):19049. doi: 10.1038/s41598-020-76122-1.
Acute respiratory distress syndrome (ARDS) is a heterogeneous condition characterized by the recruitment of large numbers of neutrophils into the lungs. Neutrophils isolated from the blood of adults with ARDS have elevated expression of interferon (IFN) stimulated genes (ISGs) associated with decreased capacity of neutrophils to kill Staphylococcus aureus and worse clinical outcomes. Neutrophil extracellular traps (NETs) are elevated in adults with ARDS. Whether pediatric ARDS (PARDS) is similarly associated with altered neutrophil expression of ISGs and neutrophil extracellular trap release is not known. Tracheal aspirate fluid and cells were collected within 72 h from seventy-seven intubated children. Primary airway neutrophils were analyzed for differential ISG expression by PCR, STAT1 phosphorylation and markers of degranulation and activation by flow cytometry. Airway fluid was analyzed for the release of NETs by myeloperoxidase-DNA complexes using an ELISA. Higher STAT1 phosphorylation, markers of neutrophil degranulation, activation and NET release were found in children with versus without PARDS. Higher NETs were detected in the airways of children with ventilator-free days less than 20 days. Increased airway cell IFN signaling, neutrophil activation, and NET production is associated with PARDS. Higher levels of airway NETs are associated with fewer ventilator-free days.
急性呼吸窘迫综合征（ARDS）是一种异质性疾病，其特征是大量中性粒细胞募集到肺部。从成人 ARDS 患者血液中分离出的中性粒细胞表达高水平的干扰素（IFN）刺激基因（ISGs），与降低杀死金黄色葡萄球菌的能力和更差的临床结局相关。ARDS 成人中性粒细胞胞外诱捕网（NETs）升高。儿科 ARDS（PARDS）是否也与中性粒细胞 ISG 表达改变和中性粒细胞胞外诱捕网释放有关尚不清楚。在 72 小时内从 77 名插管儿童中收集了气管抽吸液和细胞。通过 PCR、STAT1 磷酸化和流式细胞术分析原发性气道中性粒细胞的差异 ISG 表达、脱颗粒和活化标志物。通过 ELISA 用髓过氧化物酶-DNA 复合物分析气道液中 NET 的释放。与无 PARDS 的儿童相比，PARDS 儿童的 STAT1 磷酸化、中性粒细胞脱颗粒、活化和 NET 释放标志物更高。在呼吸机使用天数少于 20 天的儿童气道中检测到更高的 NETs。气道细胞 IFN 信号转导、中性粒细胞活化和 NET 产生增加与 PARDS 有关。气道 NETs 水平升高与呼吸机使用天数减少有关。
