Tryptophan catabolism in acute exacerbations of chronic obstructive pulmonary disease
Authors Gulcev M, Reilly C, Griffin T, Broeckling C, Sandri B, Witthuhn B, Hodgson S, Woodruff P, Wendt C
Received 5 March 2016
Accepted for publication 5 June 2016
Published 29 September 2016 Volume 2016:11(1) Pages 2435—2446
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Professor Hsiao-Chi Chuang
Peer reviewer comments 3
Editor who approved publication: Dr Richard Russell
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 Network
Introduction: 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
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