IntroductionExacerbations are a leading cause of morbidity in COPD. The objective of this study was to identify metabolomic biomarkers of acute exacerbations of COPD (AECOPD).MethodsWe 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.ResultsWe 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.ConclusionPatients with AECOPD have a unique metabolomic signature that includes a decrease in tryptophan levels consistent with an increase in indoleamine 2,3-dioxygenase activity.

BackgroundChronic Obstructive Pulmonary Disease (COPD) is a heterogeneous disease with a significant public health burden. Currently there is no biomarker that identifies those at risk of developing COPD, progression of disease or disease phenotypes. We performed metabolomic profiling of bronchoalveolar lavage fluid (BALF) from COPD patients to determine if metabolites correlated with clinical measurements such as lung function, functional status and degree of emphysema.MethodsMetabolomic components of BALF from 59 subjects with COPD and 20 healthy controls were separated by reversed-phase UPLC and analyzed by ESI-ToF mass spectrometry. We used univariate analysis and multiple regression models to investigate associations between metabolomic features and various clinical variables, such as lung function, functional status as measured by the St. George Respiratory Quotient Score and emphysema as measured by the CT density mask score.ResultsWe identified over 3900 features by mass spectrometry, many consistent with peptides. Subjects with severe COPD had increased concentration of peptides compared to controls (p < 9.526e-05). The peptide concentration correlated with spirometry, specifically pulmonary function tests associated with airflow obstruction. There was no correlation with CT density, i.e. emphysema, or functional status.ConclusionsMetabolomic profiling of BALF in COPD patients demonstrated a significant increase in peptides compared to healthy controls that associated strongly to lung function, but not emphysema or functional status.