School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom.
Department of Internal Medicine, Aberdeen Royal Infirmary, NHS Scotland, Aberdeen, United Kingdom.
Am J Physiol Lung Cell Mol Physiol. 2021 Jul 1;321(1):L79-L90. doi: 10.1152/ajplung.00077.2021. Epub 2021 May 5.
In this study, we aimed to identify acute respiratory distress syndrome (ARDS) metabolic fingerprints in selected patient cohorts and compare the metabolic profiles of direct versus indirect ARDS and hypoinflammatory versus hyperinflammatory ARDS. We hypothesized that the biological and inflammatory processes in ARDS would manifest as unique metabolomic fingerprints that set ARDS apart from other intensive care unit (ICU) conditions and could help examine ARDS subphenotypes and clinical subgroups. Patients with ARDS ( = 108) and ICU ventilated controls ( = 27) were included. Samples were randomly divided into 2/3 training and 1/3 test sets. Samples were analyzed using H nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry. Twelve proteins/cytokines were also measured. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to select the most differentiating ARDS metabolites and protein/cytokines. Predictive performance of OPLS-DA models was measured in the test set. Temporal changes of metabolites were examined as patients progressed through ARDS until clinical recovery. Metabolic profiles of direct versus indirect ARDS subgroups and hypoinflammatory versus hyperinflammatory ARDS subgroups were compared. Serum metabolomics and proteins/cytokines had similar area under receiver operator curves when distinguishing ARDS from ICU controls. Pathway analysis of ARDS differentiating metabolites identified a dominant involvement of serine-glycine metabolism. In longitudinal tracking, the identified pathway metabolites generally exhibited correction by 7-14 days, coinciding with clinical improvement. ARDS subphenotypes and clinical subgroups were metabolically distinct. However, our identified metabolic fingerprints are not ARDS diagnostic biomarkers, and further research is required to ascertain generalizability. In conclusion, patients with ARDS are metabolically different from ICU controls. ARDS subphenotypes and clinical subgroups are metabolically distinct.
在这项研究中，我们旨在确定选定患者队列中急性呼吸窘迫综合征（ARDS）的代谢特征，并比较直接性与间接性 ARDS 以及低炎症性与高炎症性 ARDS 的代谢谱。我们假设 ARDS 的生物学和炎症过程将表现为独特的代谢组学特征，使 ARDS 与其他重症监护病房（ICU）条件区分开来，并有助于检查 ARDS 的亚表型和临床亚组。纳入了 ARDS 患者（n=108）和 ICU 通气对照患者（n=27）。将样本随机分为 2/3 的训练集和 1/3 的测试集。使用 H 核磁共振波谱和气相色谱-质谱法分析样本。还测量了 12 种蛋白质/细胞因子。使用正交偏最小二乘判别分析（OPLS-DA）选择最具区分性的 ARDS 代谢物和蛋白质/细胞因子。在测试集中测量 OPLS-DA 模型的预测性能。检查患者进展为 ARDS 直至临床康复期间代谢物的时间变化。比较了直接性与间接性 ARDS 亚组以及低炎症性与高炎症性 ARDS 亚组的代谢谱。当区分 ARDS 与 ICU 对照时，血清代谢组学和蛋白质/细胞因子的受试者工作特征曲线下面积相似。区分 ARDS 的代谢物的途径分析确定丝氨酸-甘氨酸代谢的主要参与。在纵向跟踪中，所鉴定的途径代谢物通常在 7-14 天内得到纠正，与临床改善一致。ARDS 亚表型和临床亚组在代谢上是不同的。然而，我们确定的代谢指纹不是 ARDS 的诊断生物标志物，需要进一步研究以确定其普遍性。总之，ARDS 患者的代谢与 ICU 对照不同。ARDS 的亚表型和临床亚组在代谢上是不同的。
