Understanding Heterogeneity in Biologic Phenotypes of Acute Respiratory Distress Syndrome by Leukocyte Expression Profiles
Understanding Heterogeneity in Biologic Phenotypes of Acute Respiratory Distress Syndrome by Leukocyte Expression Profiles
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DOI：
10.1164/rccm.201809-1808oc
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发表时间：
2019-07-01
影响因子：
24.7
通讯作者：
Schultz, Marcus J.
中科院分区：
文献类型：
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作者：
Bos, Lieuwe D. J.;Scicluna, Brendon P.;Schultz, Marcus J.
理由：在之前的四项研究中，根据血浆蛋白标记物鉴定了急性呼吸窘迫综合征 (ARDS) 的两种生物表型。目标：确定“反应性”表型和“未炎症”表型之间的血液白细胞基因表达是否存在差异。方法：这是一项新研究，在 1.5 年期间入住两个 ICU 的脓毒症患者的现有 ARDS 患者队列中添加了血液白细胞转录组学和生物信息学分析期间。进行了规范路径分析。测量和主要结果：总共纳入了 210 名脓毒症和 ARDS 患者，其中 128 名具有反应性表型，82 名具有非炎症表型。总共 3,332/11,443 (29%) 个转录本在表型之间存在显着差异。典型通路分析显示氧化磷酸化基因上调，表明线粒体功能障碍（通路中的基因占 52%）。非炎症表型的特征是丝裂原激活蛋白激酶途径上调。结论：三分之一的基因在ARDS生物表型之间表达差异，支持ARDS亚组在病理生理学方面不可比较的观察结果。这些数据为 ARDS 患者的生物异质性提供了额外的支持，并表明针对氧化磷酸化的个性化干预方法在这种情况下至关重要。
Rationale: Two biologic phenotypes of acute respiratory distress syndrome (ARDS) have been identified based on plasma protein markers in four previous studies.Objectives: To determine if blood leukocyte gene expression is different between the "reactive" and "uninflamed" phenotype.Methods: This is a new study adding blood leukocyte transcriptomics and bioinformatics analysis to an existing patient cohort of ARDS in patients with sepsis admitted to two ICUs during a 1.5-year period. Canonical pathway analysis was performed.Measurements and Main Results: A total of 210 patients with sepsis and ARDS were included, of whom 128 had a reactive and 82 an uninflamed phenotype. A total of 3,332/11,443 (29%) transcripts were significantly different between the phenotypes. Canonical pathway analysis showed upregulation of oxidative phosphorylation genes indicative of mitochondrial dysfunction (52% of genes in pathway). The uninflamed phenotype was characterized by upregulation of mitogen-activated protein kinase pathways.Conclusions: A third of genes are differentially expressed between biologic phenotypes of ARDS supporting the observation that the subgroups of ARDS are incomparable in terms of pathophysiology. These data provide additional support for biologic heterogeneity in patients with ARDS and suggests that a personalized approach to intervention focusing on oxidative phosphorylation is pivotal in this condition.