Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California, San Francisco, California, United States.
Division of Infectious Diseases, Department of Medicine, University of California, San Francisco, California, United States.
Am J Physiol Lung Cell Mol Physiol. 2023 Mar 1;324(3):L297-L306. doi: 10.1152/ajplung.00278.2022. Epub 2023 Jan 17.
Using latent class analysis (LCA) of clinical and protein biomarkers, researchers have identified two phenotypes of the acute respiratory distress syndrome (ARDS) with divergent clinical trajectories and treatment responses. We investigated whether plasma metabolites differed among patients with LCA-derived hyperinflammatory and hypoinflammatory ARDS, and we tested the prognostic utility of adding metabolic clusters to LCA phenotypes. We analyzed data from 93 patients with ARDS and sepsis enrolled in a multicenter prospective cohort of critically ill patients, comparing 970 metabolites between the two LCA-derived phenotypes. In all, 188 metabolites were differentially abundant between the two LCA-derived phenotypes. After adjusting for age, sex, confounding medications, and comorbid liver and kidney disease, 82 metabolites remained significantly different. Patients with hyperinflammatory ARDS had reduced circulating lipids but high levels of pyruvate, lactate, and malate. Metabolic cluster and LCA-derived phenotypes were each significantly and independently associated with survival. Patients with hyperinflammatory ARDS may be experiencing a glycolytic shift leading to dysregulated lipid metabolism. Metabolic profiling offers prognostic information beyond what is captured by LCA phenotypes alone. Deeper biological profiling may identify key differences in pathogenesis among patients with ARDS and may lead to novel targeted therapies.
使用临床和蛋白质生物标志物的潜在类别分析 (LCA)，研究人员已经确定了两种急性呼吸窘迫综合征 (ARDS) 表型，它们具有不同的临床轨迹和治疗反应。我们研究了 LCA 衍生的高炎症和低炎症 ARDS 患者之间的血浆代谢物是否存在差异，并测试了将代谢物簇添加到 LCA 表型中是否具有预后价值。我们分析了来自 93 名患有 ARDS 和败血症的患者的数据，这些患者是一项多中心危重患者前瞻性队列研究的一部分，比较了两种 LCA 衍生表型之间的 970 种代谢物。共有 188 种代谢物在两种 LCA 衍生表型之间存在差异。在调整年龄、性别、混杂药物以及合并的肝和肾病后，仍有 82 种代谢物存在显著差异。高炎症性 ARDS 患者的循环脂质减少，但丙酮酸、乳酸和苹果酸水平较高。代谢物簇和 LCA 衍生的表型都与生存显著且独立相关。高炎症性 ARDS 患者可能正在经历糖酵解转移，导致脂质代谢失调。代谢组学提供了比 LCA 表型单独捕获的更具预后意义的信息。更深入的生物学分析可能会发现 ARDS 患者发病机制中的关键差异，并可能导致新的靶向治疗。
