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 journalArticle

7 Citations (Scopus)

Abstract

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
Volume11
Issue number1
DOIs
StatePublished - Sep 29 2016

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Tryptophan
Chronic Obstructive Pulmonary Disease
Indoleamine-Pyrrole 2,3,-Dioxygenase
Metabolomics
Mass Spectrometry
Biomarkers
Morbidity

Keywords

  • Chronic obstructive pulmonary disease
  • Metabolomics
  • Tryptophan

Cite this

Tryptophan catabolism in acute exacerbations of chronic obstructive pulmonary disease. / Gulcev, Makedonka; Reilly, Cavan; Griffin, Timothy J.; Broeckling, Corey D.; Sandri, Brian J.; Witthuhn, Bruce A.; Hodgson, Shane W.; Woodruff, Prescott G.; Wendt, Chris H.

In: International Journal of COPD, Vol. 11, No. 1, 29.09.2016, p. 2435-2446.

Research output: Contribution to journalArticle

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abstract = "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.",
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AU - Reilly, Cavan

AU - Griffin, Timothy J.

AU - Broeckling, Corey D.

AU - Sandri, Brian J.

AU - Witthuhn, Bruce A.

AU - Hodgson, Shane W.

AU - Woodruff, Prescott G.

AU - Wendt, Chris H.

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AB - 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.

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