Tryptophan catabolism in acute exacerbations of chronic obstructive pulmonary disease

International Journal of COPD

关键词: Chronic obstructive pulmonary disease;    tryptophan;    metabolites;    mass spectrometry;    biomarker;    exacerbation;   

DOI  :  

来源: DOAJ

【 摘 要 】

Makedonka Gulcev,1 Cavan Reilly,2 Timothy J Griffin,3 Corey D Broeckling,4 Brian J Sandri,1 Bruce A Witthuhn,3 Shane W Hodgson,1 Prescott G Woodruff,5 Chris H Wendt1,6,*1Department of Medicine, 2Division of Biostatistics, School of Public Health, 3Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA; 4Department of Computer Science, Colorado State University, Fort Collins, CO, USA; 5Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine and the CVRI, University of California, San Francisco, CA, USA; 6Department of Medicine, Minneapolis VA Medical Center, Minneapolis, MN, USA*For the COPD Clinical Research NetworkIntroduction: Exacerbations are a leading cause of morbidity in COPD. The objective of this study was to identify metabolomic biomarkers of acute exacerbations of COPD (AECOPD). Methods: We measured metabolites via mass spectrometry (MS) in plasma drawn within 24 hours of admission to the hospital for 33 patients with an AECOPD (day 0) and 30 days later and for 65 matched controls. Individual metabolites were measured via selective reaction monitoring with mass spectrometry. We used a mixed-effect model to compare metabolite levels in cases compared to controls and a paired t-test to test for differences between days 0 and 30 in the AECOPD group. Results: We identified 377 analytes at a false discovery rate of 5% that differed between cases (day 0) and controls, and 31 analytes that differed in the AECOPD cases between day 0 and day 30 (false discovery rate: 5%). Tryptophan was decreased at day 0 of AECOPD compared to controls corresponding to an increase in indoleamine 2,3-dioxygenase activity. Conclusion: Patients with AECOPD have a unique metabolomic signature that includes a decrease in tryptophan levels consistent with an increase in indoleamine 2,3-dioxygenase activity.Keywords: Chronic Obstructive Pulmonary Disease, metabolomics, tryptophan

【 授权许可】

Unknown