Metabolomic signatures predict seven-year mortality in clinically stable COPD patients

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• dc.contributor.author Enríquez Rodríguez, César Jessé
• dc.contributor.author Agranovich, Bella
• dc.contributor.author Pascual Guàrdia, Sergi, 1979-
• dc.contributor.author Faner, Rosa
• dc.contributor.author Camps-Ubach, Ramon
• dc.contributor.author Castro-Acosta, Ady Angélica
• dc.contributor.author Lopez-Campos, Jose Luis
• dc.contributor.author Peces-Barba Romero, Germán
• dc.contributor.author Seijó Maceiras, Luis
• dc.contributor.author Caguana Vélez, Oswaldo Antonio
• dc.contributor.author Rodriguez-Chiaradia, Diego Agustín
• dc.contributor.author Barreiro Portela, Esther
• dc.contributor.author Monsó Molas, Eduard
• dc.contributor.author Cosío, Borja G.
• dc.contributor.author Abramovich, Ifat
• dc.contributor.author Agustí, Alvar
• dc.contributor.author Casadevall Fusté, Carme
• dc.contributor.author Gea Guiral, Joaquim
• dc.date.accessioned 2025-09-09T06:31:50Z
• dc.date.available 2025-09-09T06:31:50Z
• dc.date.issued 2025
• dc.description.abstract Chronic Obstructive Pulmonary Disease (COPD) is a complex condition with high mortality. Early identification of patients at increased risk of death remains a major clinical challenge. This pilot study aimed to explore whether plasma metabolomic profiling could aid in the prediction of long-term (7-year) mortality and provide insight into potential underlying mechanisms. Plasma samples from 54 randomly selected stable COPD patients were analyzed using both untargeted and semi-targeted LC-MS approaches. After excluding patients with unclear death data, non-COPD-related deaths and metabolomic outliers, 41 individuals were included in the final analysis. During follow-up, 13 patients (32%) died, and 28 survived. Univariate analysis identified 12 metabolites—mainly amino acids—that differed significantly between the two groups. Functional analysis suggested a significant disruption in energy production pathways. Predictive models developed using machine learning algorithms, consisting of either ten metabolites alone or nine metabolites plus FEV1, achieved high accuracy for 7-year mortality prediction, with the latter model performing slightly better. Internal validation was conducted using five-fold cross-validation. While exploratory, these findings support the hypothesis that early metabolic alterations, particularly in energy pathways, may contribute to long-term mortality risk in stable COPD patients, and could complement traditional prognostic markers such as FEV1.en
• dc.description.sponsorship This study was supported by joint funding from the Spanish Ministry of Economy and Competitiveness and the European Union (project SAF2014-54371); the Instituto de Salud Carlos III (ISCIII) and the European Union (projects PI21/00785 and M-BAE BA22/00009); SEPAR Grants (2016, and 2019); a SOCAP Grant (2020); and an unrestricted grant from Menarini Spain (2015–2019). César Jessé Enríquez-Rodríguez holds a predoctoral fellowship (PFIS, ref. FI22/00003) and a Research Personnel Mobility Grant (M-AES MV23/00012), both awarded by ISCIII and co-funded by the European Union.en
• dc.format.mimetype application/pdf
• dc.identifier.citation Enríquez-Rodríguez CJ, Agranovich B, Pascual-Guàrdia S, Faner R, Camps-Ubach R, Castro-Acosta A, et al. Metabolomic signatures predict seven-year mortality in clinically stable COPD patients. Int J Mol Sci. 2025 Jul 1;26(13):6373. DOI: 10.3390/ijms26136373
• dc.identifier.doi http://dx.doi.org/10.3390/ijms26136373
• dc.identifier.issn 1422-0067
• dc.identifier.uri http://hdl.handle.net/10230/71162
• dc.language.iso eng
• dc.publisher MDPI
• dc.relation.ispartof International Journal of Molecular Sciences. 2025 Jul 1;26(13):6373
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2014-54371
• dc.rights © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword COPDen
• dc.subject.keyword Mortalityen
• dc.subject.keyword Metabolomicsen
• dc.subject.keyword Energyen
• dc.subject.keyword Amino acidsen
• dc.subject.keyword Redoxen
• dc.subject.keyword Microbiotaen
• dc.title Metabolomic signatures predict seven-year mortality in clinically stable COPD patientsen
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion