Plasma Metabolomes Identify Distinct Asthma Metabotypes: Findings From the COREA Cohort

Area of Science:

• Metabolomics and Systems Biology
• Respiratory Medicine
• Personalized Medicine

Background:

• Current asthma classification based on phenotypes has limitations.
• Existing biomarkers for asthma lack specificity and clinical accessibility.
• Plasma metabolomics offers a promising approach for classifying asthma by reflecting disease-specific metabolic states.

Purpose of the Study:

• To identify distinct metabolic subgroups (metabotypes) within adult asthma patients.
• To utilize plasma metabolomics for a more precise asthma classification.
• To explore the potential for personalized asthma treatment based on identified metabotypes.

Main Methods:

• Analysis of plasma samples from 407 adult asthma patients (COREA cohort).
• Utilized liquid chromatography-mass spectrometry (LC-MS) with Biocrates AbsoluteIDQ p400 HR kit.
• Applied k-means clustering to 281 standardized metabolites, with cluster number determined by multi-criteria assessment.

Main Results:

• Identified four distinct asthma metabotypes characterized by unique lipid-class signatures.
• Group 1: Elevated ether-linked phosphatidylcholines, younger patients, early onset, female predominance.
• Group 2: Elevated lyso-phosphatidylcholines, altered amino acid metabolism (glutamate/glutamine), intermediate non-T2-high.
• Group 3: Reduced sphingomyelins and phosphatidylcholines, middle-aged, non-obese.
• Group 4: Markedly elevated triacylglycerols (TG) and diacylglycerols (DG), highest BMI, obesity-related non-T2 metabotype, robust signature independent of BMI, age, sex.

Conclusions:

• Plasma metabolomics successfully identified clinically meaningful asthma metabotypes.
• These findings support the integration of metabolomic profiling into personalized asthma management.
• Metabolomic signatures offer a novel approach to stratify asthma patients for tailored therapies.