Plasma Metabolomic Signature Accurately Discriminates Frequent Exacerbators among COPD Patients
Metabolomic substrate in COPD
COPD is characterised by recurrent exacerbations, which are strongly associated with increased mortality and accelerated disease progression.
It has been proposed that the frequent exacerbator (FE) phenotype is biologically distinct from those of non-frequent exacerbators (NFE) and controls. However, comprehensive metabolomic profiling remains unexplored.
Plasma metabolomic profiling to characterise the COPD phenotype
We performed LC-MS/MS untargeted metabolomics analysis on plasma samples from 226 participants (66 ± 9 y.o, 34% ♀) from the BIOMEPOC cohort: 35 FE, 127 NFE, and 64 controls.
We analysed the differences between the groups using a t-test with empirical Bayes shrinkage, adjusting for sex, age, and FEV1.
Additionally, we developed AI models using Flame to assess the predictive potential of metabolomic profiles as a clinical management tool.
Distinct metabolomic substrate in frequent exacerbators
Compared to controls, 49 metabolites were significantly altered in the FE group and 14 in the NFE group (FDR adj.<0.05).
8 underrepresented metabolites (2-Deoxy-D-Glucose, urate, nicotinamide, kynurenine, 6-Methylindole and 4-Indolecarbaldehyde, testosterone sulphate, and L-carnitine) distinguished FE from NFE, suggesting disturbances in energy metabolism, antioxidant defence, immunomodulation, and hormonal function in FE.
Predictive accuracy of the metabolomic substrate in COPD
This signature achieved a >95% accuracy, identifying FE among the three groups in a 5-fold cross-validation.
Evidence for a specific metabolomic substrate in COPD
Our findings provide evidence for a specific metabolomic substrate that characterises the FE phenotype in COPD, distinct from those of NFE and healthy controls. Further mechanistic investigations and validation are required.
Authors
César Jessé Enríquez Rodríguez, Carme Casadevall, Sergi Pascual-Guardia, Rosa Faner, José Luís López-Campos, Ady Castro-Acosta, Gregorio Peces-Barba, Luis Miguel Seijo, Eduard Monsó, Esther Barreiro, Borja García-Cosío, Diego Rodríguez-Chiaradia, Ori Shalev, Alvar Agustí, Joaquim Gea, On Behalf Biomepoc Group
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Fecha de publicación
Published online 18 November 2025
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