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Int. J. Mol. Sci. 2018, 19(3), 666; https://doi.org/10.3390/ijms19030666

Phenotyping of Chronic Obstructive Pulmonary Disease Based on the Integration of Metabolomes and Clinical Characteristics

1
Department of Biochemistry, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, 50411 Tartu, Estonia
2
Centre of Excellence for Genomics and Translational Medicine, Riia 23b, 51010 Tartu, Estonia
3
Estonian Health Insurance Fund, Lastekodu 48, 10144 Tallinn, Estonia
4
Department of Pulmonology, University of Tartu, Puusepa 8, 51014 Tartu, Estonia
5
Lung Clinic, Tartu University Hospital, Puusepa 8, 51014 Tartu, Estonia
*
Author to whom correspondence should be addressed.
Received: 21 January 2018 / Revised: 21 February 2018 / Accepted: 24 February 2018 / Published: 27 February 2018
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Abstract

Apart from the refined management-oriented clinical stratification of chronic obstructive pulmonary disease (COPD), the molecular pathologies behind this highly prevalent disease have remained obscure. The aim of this study was the characterization of patients with COPD, based on the metabolomic profiling of peripheral blood and exhaled breath condensate (EBC) within the context of defined clinical and demographic variables. Mass-spectrometry-based targeted analysis of serum metabolites (mainly amino acids and lipid species), untargeted profiles of serum and EBC of patients with COPD of different clinical characteristics (n = 25) and control individuals (n = 21) were performed. From the combined clinical/demographic and metabolomics data, associations between clinical/demographic and metabolic parameters were searched and a de novo phenotyping for COPD was attempted. Adjoining the clinical parameters, sphingomyelins were the best to differentiate COPD patients from controls. Unsaturated fatty acid-containing lipids, ornithine metabolism and plasma protein composition-associated signals from the untargeted analysis differentiated the Global Initiative for COPD (GOLD) categories. Hierarchical clustering did not reveal a clinical-metabolomic stratification superior to the strata set by the GOLD consensus. We conclude that while metabolomics approaches are good for finding biomarkers and clarifying the mechanism of the disease, there are no distinct co-variate independent clinical-metabolic phenotypes. View Full-Text
Keywords: chronic obstructive pulmonary disease; metabolomics; exhaled breath condensate; phenotyping; GOLD stratification; sphingomyelin chronic obstructive pulmonary disease; metabolomics; exhaled breath condensate; phenotyping; GOLD stratification; sphingomyelin
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Kilk, K.; Aug, A.; Ottas, A.; Soomets, U.; Altraja, S.; Altraja, A. Phenotyping of Chronic Obstructive Pulmonary Disease Based on the Integration of Metabolomes and Clinical Characteristics. Int. J. Mol. Sci. 2018, 19, 666.

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