Serum metabolomics analysis of patients with chronic obstructive pulmonary disease and 'frequent exacerbator' phenotype

ABSTRACT:

BACKGROUND: Chronic obstructive pulmonary disease (COPD) exacerbations significantly contribute to morbidity and mortality. The complex nature of COPD presents challenges in accurately predicting and understanding frequent exacerbations.

OBJECTIVE: This study aimed to investigate the metabolic characteristics of frequent exacerbation of COPD (COPD-FE) phenotype, identify potential metabolic biomarkers associated with COPD-FE risk and explore underlying pathogenic mechanisms.

METHODS: An internal cohort of 30 stable COPD patients was recruited. A widely targeted metabolomics approach was employed to detect and compare serum metabolite expressions between patients with COPD-FE and non-frequent exacerbations (COPD-NE). Subsequently, bioinformatics analysis was utilized for pathway enrichment of the identified metabolites; Spearman correlation analysis explored associations between metabolites and clinical indicators, and receiver operating characteristic (ROC) analysis assessed the predictive performance of identified metabolites. An external cohort of 20 patients with COPD validated findings from the internal cohort.

RESULTS: Out of 484 detected metabolites, 25 exhibited significant differences between COPD-FE and COPD-NE. Metabolomic analysis revealed differences in lipid, energy, amino acid and immunity pathways. Spearman correlation analysis showed associations between metabolites and clinical indicators of acute exacerbation risk. ROC analysis revealed that D-fructose 1,6-bisphosphate (AUC=0.871), arginine (AUC=0.836), L-2-Hydroxyglutarate (L-2HG, AUC=0.849), Diacylglycerol (DG)(16:0/20:5) (AUC=0.827), DG(16:0/20:4) (AUC=0.818) and carnitine-C18:2 (AUC=0.804) had area under the curve (AUC) values above 0.8, highlighting their superior discriminative capacity between the two groups. External validation results showed that DG(16:0/20:5), DG(16:0/20:4), carnitine-C18:2 and L-2HG were significantly different between COPD-FE patients and COPD-NE patients (p-value<0.05).

CONCLUSION: This study offers insights into early identification, mechanistic understanding and personalized management of COPD-FE phenotype.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

SUBMITTER: huanzhang ding 

PROVIDER: MTBLS9119 | MetaboLights | 2024-02-23

REPOSITORIES: MetaboLights