Serum metabolomic signatures of fatty acid oxidation defects differentiate host-response subphenotypes of acute respiratory distress syndrome

Respiratory Research

Research

Rama K. Mallampalli¹  Stacy G. Wendell²  Steven J. Mullett²  Janet S. Lee³  Benjamin Zuchelkowski⁴  Seyed Mehdi Nouraie⁴  Yingze Zhang⁴  Tomeka L. Suber⁵  Prabir Ray⁵  Georgios D. Kitsios⁵  Anuradha Ray⁵  Bryan J. McVerry⁵  Faraaz Shah⁶  William Bain⁶ 

[1] Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA;Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA;Division of Pulmonary and Critical Care Medicine, Department of Medicine, Washington University at St. Louis, St. Louis, MO, USA;Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, Montefiore Hospital, University of Pittsburgh School of Medicine, NW 628, 3459 Fifth Avenue, 15213, Pittsburgh, PA, USA;Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, Montefiore Hospital, University of Pittsburgh School of Medicine, NW 628, 3459 Fifth Avenue, 15213, Pittsburgh, PA, USA;Acute Lung Injury Center of Excellence, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA;Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, Montefiore Hospital, University of Pittsburgh School of Medicine, NW 628, 3459 Fifth Avenue, 15213, Pittsburgh, PA, USA;Acute Lung Injury Center of Excellence, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA;Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA, USA;

关键词: Metabolomics;    Acute respiratory distress syndrome;    Subphenotypes;    Acylcarnitines;    Fatty acid oxidation;   

DOI  :  10.1186/s12931-023-02447-w

 received in 2022-11-19, accepted in 2023-05-09,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundFatty acid oxidation (FAO) defects have been implicated in experimental models of acute lung injury and associated with poor outcomes in critical illness. In this study, we examined acylcarnitine profiles and 3-methylhistidine as markers of FAO defects and skeletal muscle catabolism, respectively, in patients with acute respiratory failure. We determined whether these metabolites were associated with host-response ARDS subphenotypes, inflammatory biomarkers, and clinical outcomes in acute respiratory failure.MethodsIn a nested case–control cohort study, we performed targeted analysis of serum metabolites of patients intubated for airway protection (airway controls), Class 1 (hypoinflammatory), and Class 2 (hyperinflammatory) ARDS patients (N = 50 per group) during early initiation of mechanical ventilation. Relative amounts were quantified by liquid chromatography high resolution mass spectrometry using isotope-labeled standards and analyzed with plasma biomarkers and clinical data.ResultsOf the acylcarnitines analyzed, octanoylcarnitine levels were twofold increased in Class 2 ARDS relative to Class 1 ARDS or airway controls (P = 0.0004 and < 0.0001, respectively) and was positively associated with Class 2 by quantile g-computation analysis (P = 0.004). In addition, acetylcarnitine and 3-methylhistidine were increased in Class 2 relative to Class 1 and positively correlated with inflammatory biomarkers. In all patients within the study with acute respiratory failure, increased 3-methylhistidine was observed in non-survivors at 30 days (P = 0.0018), while octanoylcarnitine was increased in patients requiring vasopressor support but not in non-survivors (P = 0.0001 and P = 0.28, respectively).ConclusionsThis study demonstrates that increased levels of acetylcarnitine, octanoylcarnitine, and 3-methylhistidine distinguish Class 2 from Class 1 ARDS patients and airway controls. Octanoylcarnitine and 3-methylhistidine were associated with poor outcomes in patients with acute respiratory failure across the cohort independent of etiology or host-response subphenotype. These findings suggest a role for serum metabolites as biomarkers in ARDS and poor outcomes in critically ill patients early in the clinical course.

【 授权许可】

CC BY   
© The Author(s) 2023

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