دورية أكاديمية
Serum metabolomic signatures of fatty acid oxidation defects differentiate host-response subphenotypes of acute respiratory distress syndrome.
العنوان: | Serum metabolomic signatures of fatty acid oxidation defects differentiate host-response subphenotypes of acute respiratory distress syndrome. |
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المؤلفون: | Suber TL; 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, Pittsburgh, PA, 15213, USA. subertl2@upmc.edu.; Acute Lung Injury Center of Excellence, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. subertl2@upmc.edu., Wendell SG; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Mullett SJ; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Zuchelkowski B; 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, Pittsburgh, PA, 15213, USA., Bain W; 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, Pittsburgh, PA, 15213, 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., Kitsios GD; 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, Pittsburgh, PA, 15213, USA.; Acute Lung Injury Center of Excellence, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., McVerry BJ; 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, Pittsburgh, PA, 15213, USA.; Acute Lung Injury Center of Excellence, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Ray P; 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, Pittsburgh, PA, 15213, USA.; Acute Lung Injury Center of Excellence, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Ray A; 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, Pittsburgh, PA, 15213, USA.; Acute Lung Injury Center of Excellence, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Mallampalli RK; Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA., Zhang Y; 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, Pittsburgh, PA, 15213, USA., Shah F; 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, Pittsburgh, PA, 15213, 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., Nouraie SM; 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, Pittsburgh, PA, 15213, USA., Lee JS; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Washington University at St. Louis, St. Louis, MO, USA. |
المصدر: | Respiratory research [Respir Res] 2023 May 20; Vol. 24 (1), pp. 136. Date of Electronic Publication: 2023 May 20. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: BioMed Central Ltd Country of Publication: England NLM ID: 101090633 Publication Model: Electronic Cited Medium: Internet ISSN: 1465-993X (Electronic) Linking ISSN: 14659921 NLM ISO Abbreviation: Respir Res Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 2001- : London : BioMed Central Ltd. Original Publication: London : Current Science Ltd., c2000- |
مواضيع طبية MeSH: | Respiratory Distress Syndrome*/diagnosis , Respiratory Insufficiency*/diagnosis , Respiratory Insufficiency*/complications, Humans ; Acetylcarnitine ; Case-Control Studies ; Biomarkers ; Fatty Acids |
مستخلص: | Background: Fatty 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. Methods: In 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. Results: Of 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). Conclusions: This 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. (© 2023. The Author(s).) |
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معلومات مُعتمدة: | K24 HL143285 United States HL NHLBI NIH HHS; R01 HL142084 United States HL NHLBI NIH HHS; P01 HL114453 United States HL NHLBI NIH HHS; KL2 TR001856 United States NH NIH HHS; S10ODS023402 United States NH NIH HHS; S10 OD023402 United States OD NIH HHS; P01HL114453 United States NH NIH HHS; R01 HL136143 United States HL NHLBI NIH HHS |
فهرسة مساهمة: | Keywords: Acute respiratory distress syndrome; Acylcarnitines; Fatty acid oxidation; Metabolomics; Subphenotypes |
المشرفين على المادة: | S1HB7P0O16 (octanoylcarnitine) 6DH1W9VH8Q (Acetylcarnitine) 0 (Biomarkers) 0 (Fatty Acids) |
تواريخ الأحداث: | Date Created: 20230520 Date Completed: 20230522 Latest Revision: 20240618 |
رمز التحديث: | 20240618 |
مُعرف محوري في PubMed: | PMC10199668 |
DOI: | 10.1186/s12931-023-02447-w |
PMID: | 37210531 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1465-993X |
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DOI: | 10.1186/s12931-023-02447-w |