한빛사논문
Youjin Chang1, Hyun Ju Yoo2, Su Jung Kim2, Kwangha Lee3, Chae‑Man Lim4, Sang‑Bum Hong4, Younsuck Koh4 and Jin Won Huh4*
1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Inje University Sanggye Paik Hospital, Seoul, Republic of Korea.
2Department of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
3Department of Internal Medicine, Pusan National University School of Medicine, Busan, Republic of Korea.
4Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic‑ro 43‑gil, Songpa‑gu, Seoul 05505, Republic of Korea.
Corresponding author : Correspondence to Jin Won Huh.
Abstract
Background: Acute respiratory distress syndrome (ARDS) is etiologically and clinically a heterogeneous disease. Its diagnostic characteristics and subtype classification, and the application of these features to treatment, have been of considerable interest. Metabolomics is becoming important for identifying ARDS biology and distinguishing its subtypes. This study aimed to identify metabolites that could distinguish sepsis-induced ARDS patients from non-ARDS controls, using a targeted metabolomics approach, and to identify whether sepsis-induced direct and sepsis-induced indirect ARDS are metabolically distinct groups, and if so, confirm their metabolites and associated pathways.
Methods: This study retrospectively analyzed 54 samples of ARDS patients from a sepsis registry that was prospectively collected from March 2011 to February 2018, along with 30 non-ARDS controls. The cohort was divided into direct and indirect ARDS. Metabolite concentrations of five analyte classes (energy metabolism, free fatty acids, amino acids, phospholipids, sphingolipids) were measured using liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry by targeted metabolomics.
Results: In total, 186 metabolites were detected. Among them, 102 metabolites could differentiate sepsis-induced ARDS patients from the non-ARDS controls, while 14 metabolites could discriminate sepsis-induced ARDS subphenotypes. Using partial least-squares discriminant analysis, we showed that sepsis-induced ARDS patients were metabolically distinct from the non-ARDS controls. The main distinguishing metabolites were lysophosphatidylethanolamine (lysoPE) plasmalogen, PE plasmalogens, and phosphatidylcholines (PCs). Sepsis-induced direct and indirect ARDS were also metabolically distinct subgroups, with differences in lysoPCs. Glycerophospholipid and sphingolipid metabolism were the most significant metabolic pathways involved in sepsis-induced ARDS biology and in sepsis-induced direct/indirect ARDS, respectively.
Conclusion: Our study demonstrated a marked difference in metabolic patterns between sepsis-induced ARDS patients and non-ARDS controls, and between sepsis-induced direct and indirect ARDS subpheonotypes. The identified metabolites and pathways can provide clues relevant to the diagnosis and treatment of individuals with ARDS.
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