title: Tryptophan catabolism in acute exacerbations of chronic obstructive pulmonary disease.
abstract: BACKGROUND
  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 pairedt-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine.
authors.forename: Makedonka
authors.initials: M
authors.lastname: Gulcev
authors.affiliation: Division of Biostatistics, School of Public Health.
authors.forename: Cavan
authors.initials: C
authors.lastname: Reilly
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Griffin
authors.affiliation: Department of Computer Science, Colorado State University, Fort Collins, CO, USA.
authors.forename: Corey D
authors.initials: CD
authors.lastname: Broeckling
authors.affiliation: Department of Medicine.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Sandri
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Witthuhn
authors.affiliation: Department of Medicine.
authors.forename: Shane W
authors.initials: SW
authors.lastname: Hodgson
authors.affiliation: Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine and the CVRI, University of California, San Francisco, CA, USA.
authors.forename: Prescott G
authors.initials: PG
authors.lastname: Woodruff
authors.affiliation: Department of Medicine; Department of Medicine, Minneapolis VA Medical Center, Minneapolis, MN, USA.
authors.forename: Chris H
authors.initials: CH
authors.lastname: Wendt
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D006760:Hospitalization; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D008168:Lung / Q000503:physiopathology*; D008297:Male; D013058:Mass Spectrometry; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D011237:Predictive Value of Tests; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D013997:Time Factors; D014364:Tryptophan / Q000097:blood*
chemical_list: D015415:Biomarkers; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D014364:Tryptophan
keywords: Chronic Obstructive Pulmonary Disease; metabolomics; tryptophan