Department of Anesthesiology, Division of Critical Care Medicine, University of Michigan Medical School, 4172 Cardiovascular Center, 1500 East Medical Center Drive, SPC 5861, Ann Arbor, MI, 48109, USA.
Michigan Center for Integrative Research in Critical Care, University of Michigan, Ann Arbor, Michigan, USA.
Respir Res. 2018 Apr 10;19(1):60. doi: 10.1186/s12931-018-0758-3.
It is unknown if the plasma lipidome is a useful tool for improving our understanding of the acute respiratory distress syndrome (ARDS). Therefore, we measured the plasma lipidome of individuals with ARDS at two time-points to determine if changes in the plasma lipidome distinguished survivors from non-survivors. We hypothesized that both the absolute concentration and change in concentration over time of plasma lipids are associated with 28-day mortality in this population.
Samples for this longitudinal observational cohort study were collected at multiple tertiary-care academic medical centers as part of a previous multicenter clinical trial. A mass spectrometry shot-gun lipidomic assay was used to quantify the lipidome in plasma samples from 30 individuals. Samples from two different days were analyzed for each subject. After removing lipids with a coefficient of variation > 30%, differences between cohorts were identified using repeated measures analysis of variance. The false discovery rate was used to adjust for multiple comparisons. Relationships between significant compounds were explored using hierarchical clustering of the Pearson correlation coefficients and the magnitude of these relationships was described using receiver operating characteristic curves.
The mass spectrometry assay reliably measured 359 lipids. After adjusting for multiple comparisons, 90 compounds differed between survivors and non-survivors. Survivors had higher levels for each of these lipids except for five membrane lipids. Glycerolipids, particularly those containing polyunsaturated fatty acid side-chains, represented many of the lipids with higher concentrations in survivors. The change in lipid concentration over time did not differ between survivors and non-survivors.
The concentration of multiple plasma lipids is associated with mortality in this group of critically ill patients with ARDS. Absolute lipid levels provided more information than the change in concentration over time. These findings support future research aimed at integrating lipidomics into critical care medicine.
目前尚不清楚血浆脂质组是否可作为一种有用的工具，帮助我们深入了解急性呼吸窘迫综合征（ARDS）。因此，我们在两个时间点测量了 ARDS 患者的血浆脂质组，以确定血浆脂质组的变化是否可以区分存活者和非存活者。我们假设，在该人群中，血浆脂质的绝对浓度及其随时间的变化均与 28 天死亡率相关。
本纵向观察性队列研究的样本采集于多家三级保健学术医疗中心，是先前多中心临床试验的一部分。采用质谱 shotgun 脂质组学分析方法对 30 名患者的血浆样本进行脂质组定量分析。每个患者的两个不同日期的样本均进行了分析。在去除变异系数>30%的脂质后，采用重复测量方差分析比较队列间的差异。采用假发现率校正进行多重比较。采用皮尔逊相关系数的层次聚类分析探索显著化合物之间的关系，并使用受试者工作特征曲线描述这些关系的幅度。
质谱分析可靠地测量了 359 种脂质。在进行多重比较校正后，存活者和非存活者之间有 90 种化合物存在差异。除了 5 种膜脂质外，存活者的每种脂质水平均较高。甘油磷脂，尤其是含有多不饱和脂肪酸侧链的甘油磷脂，代表了存活者中许多浓度较高的脂质。存活者和非存活者的脂质浓度随时间的变化无差异。
在这组患有 ARDS 的危重症患者中，多种血浆脂质的浓度与死亡率相关。与浓度随时间的变化相比，脂质的绝对水平提供了更多信息。这些发现支持未来将脂质组学纳入重症监护医学的研究。
