Tryptophan catabolism in acute exacerbations of chronic obstructive pulmonary disease

Makedonka Gulcev, Cavan Reilly, Timothy J. Griffin, Corey D. Broeckling, Brian J. Sandri, Bruce A. Witthuhn, Shane W. Hodgson, Prescott G. Woodruff, Chris H. Wendt

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2435-2446
Number of pages12
JournalInternational Journal of COPD
Issue number1
StatePublished - Sep 29 2016

Bibliographical note

Funding Information:
This work was supported by grants from the National Heart, Lung, and Blood Institute of the National Institutes of HealthNIH (U10 HL074407, U10 HL074408, U10HL074409, U10 HL074416, U10 HL074418, U10 HL074422, U10 HL074424, U10 HL074428, U10 HL074431, U10 HL074439, and U10 HL074441) and National Institutes of Health NIHT32 HL07741 (Sandri).

Publisher Copyright:
© 2016 Gulcev et al.


  • Chronic obstructive pulmonary disease
  • Metabolomics
  • Tryptophan


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