社区获得性肺炎患者急性呼吸窘迫综合征的核磁共振代谢组学特征。
Metabolomics profile in acute respiratory distress syndrome by nuclear magnetic resonance spectroscopy in patients with community-acquired pneumonia.
机构信息
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang Street, Wenzhou, 325000, China.
Institute of Metabonomics & Medical NMR, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
出版信息
Respir Res. 2022 Jun 27;23(1):172. doi: 10.1186/s12931-022-02075-w.
BACKGROUND
Acute respiratory distress syndrome (ARDS) is a challenging clinical problem. Discovering the potential metabolic alterations underlying the ARDS is important to identify novel therapeutic target and improve the prognosis. Serum and urine metabolites can reflect systemic and local changes and could help understanding metabolic characterization of community-acquired pneumonia (CAP) with ARDS.
METHODS
Clinical data of patients with suspected CAP at the First Affiliated Hospital of Wenzhou Medical University were collected from May 2020 to February 2021. Consecutive patients with CAP were enrolled and divided into two groups: CAP with and without ARDS groups. H nuclear magnetic resonance-based metabolomics analyses of serum and urine samples were performed before and after treatment in CAP with ARDS (n = 43) and CAP without ARDS (n = 45) groups. Differences metabolites were identifed in CAP with ARDS. Furthermore, the receiver operating characteristic (ROC) curve was utilized to identify panels of significant metabolites for evaluating therapeutic effects on CAP with ARDS. The correlation heatmap was analyzed to further display the relationship between metabolites and clinical characteristics.
RESULTS
A total of 20 and 42 metabolites were identified in the serum and urine samples, respectively. Serum metabolic changes were mainly involved in energy, lipid, and amino acid metabolisms, while urine metabolic changes were mainly involved in energy metabolism. Elevated levels of serum 3-hydroxybutyrate, lactate, acetone, acetoacetate, and decreased levels of serum leucine, choline, and urine creatine and creatinine were detected in CAP with ARDS relative to CAP without ARDS. Serum metabolites 3-hydroxybutyrate, acetone, acetoacetate, citrate, choline and urine metabolite 1-methylnicotinamide were identified as a potential biomarkers for assessing therapeutic effects on CAP with ARDS, and with AUCs of 0.866 and 0.795, respectively. Moreover, the ROC curve analysis revealed that combined characteristic serum and urine metabolites exhibited a better classification system for assessing therapeutic effects on CAP with ARDS, with a AUC value of 0.952. In addition, differential metabolites strongly correlated with clinical parameters in patients with CAP with ARDS.
CONCLUSIONS
Serum- and urine-based metabolomics analyses identified characteristic metabolic alterations in CAP with ARDS and might provide promising circulatory markers for evaluating therapeutic effects on CAP with ARDS.
背景
急性呼吸窘迫综合征（ARDS）是一个具有挑战性的临床问题。发现 ARDS 潜在的代谢改变对于确定新的治疗靶点和改善预后非常重要。血清和尿液代谢物可以反映全身和局部变化，有助于了解伴有 ARDS 的社区获得性肺炎（CAP）的代谢特征。
方法
收集温州医科大学附属第一医院 2020 年 5 月至 2021 年 2 月疑似 CAP 患者的临床资料。连续纳入 CAP 患者，根据是否并发 ARDS 将其分为 CAP 合并 ARDS 组（n=43）和 CAP 不合并 ARDS 组（n=45）。对 CAP 合并 ARDS 患者（n=43）和 CAP 不合并 ARDS 患者（n=45）治疗前后的血清和尿液样本进行基于 H 核磁共振的代谢组学分析。在 CAP 合并 ARDS 组中鉴定出差异代谢物。此外，还利用受试者工作特征（ROC）曲线来识别用于评估 CAP 合并 ARDS 治疗效果的显著代谢物组合。通过分析相关热图进一步显示代谢物与临床特征之间的关系。
结果
在血清和尿液样本中分别鉴定出 20 种和 42 种代谢物。血清代谢变化主要涉及能量、脂质和氨基酸代谢，而尿液代谢变化主要涉及能量代谢。与 CAP 不合并 ARDS 组相比，CAP 合并 ARDS 组血清中 3-羟丁酸、乳酸、丙酮、乙酰乙酸和亮氨酸、胆碱以及尿液中肌酸和肌酐水平升高，而 3-羟丁酸、丙酮、乙酰乙酸、柠檬酸、胆碱和尿液中 1-甲基烟酰胺水平降低。血清代谢物 3-羟丁酸、丙酮、乙酰乙酸、柠檬酸、胆碱和尿液代谢物 1-甲基烟酰胺被鉴定为评估 CAP 合并 ARDS 治疗效果的潜在生物标志物，其 AUC 值分别为 0.866 和 0.795。此外，ROC 曲线分析表明，联合特征血清和尿液代谢物对评估 CAP 合并 ARDS 的治疗效果具有更好的分类系统，AUC 值为 0.952。此外，差异代谢物与 CAP 合并 ARDS 患者的临床参数密切相关。
结论
基于血清和尿液的代谢组学分析鉴定出 CAP 合并 ARDS 的特征代谢改变，可能为评估 CAP 合并 ARDS 的治疗效果提供有前景的循环标志物。
Zotero 插件