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Clinical & Experimental Allergy

Serum metabolomics reveals pathways and biomarkers associated with asthma pathogenesis

Authors

  • J. Jung,

    1. Integrated Metabolomics Research Group, Seoul Center, Korea Basic Science Institute, Seoul, Republic of Korea
    2. Department of Physiology, College of Oriental Medicine, Wonkwang University, Iksan, Republic of Korea
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    • J. Jung and S.-H. Kim contributed equally in this work.
  • S.-H. Kim,

    1. Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Republic of Korea
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    • J. Jung and S.-H. Kim contributed equally in this work.
  • H.-S. Lee,

    1. Department of Physiology, College of Oriental Medicine, Wonkwang University, Iksan, Republic of Korea
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  • G. S. Choi,

    1. Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Republic of Korea
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  • Y.-S. Jung,

    1. Integrated Metabolomics Research Group, Seoul Center, Korea Basic Science Institute, Seoul, Republic of Korea
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  • D. H. Ryu,

    1. Department of Chemistry, Sungkyunkwan University, Suwon, Republic of Korea
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  • H.-S. Park,

    Corresponding author
    1. Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Republic of Korea
    • Integrated Metabolomics Research Group, Seoul Center, Korea Basic Science Institute, Seoul, Republic of Korea
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  • G.-S. Hwang

    Corresponding author
    1. Graduate School of Analytical Science and Technology, Chungnam University, Daejeon, Republic of Korea
    • Integrated Metabolomics Research Group, Seoul Center, Korea Basic Science Institute, Seoul, Republic of Korea
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Correspondence:

Geum-Sook Hwang, Korea Basic Science Institute, Seoul, Korea.

E-mail gshwang@kbsi.re.kr and Hae-Sim Park, Ajou University School of Medicine, Suwon Korea.

E-mail hspark@ajou.ac.kr

Summary

Background

Asthma is a chronic inflammatory disease caused by complex interactions of genetic, epigenetic, and environmental factors. For this reason, new approaches are required to clarify the pathogenesis of asthma by systemic review.

Objective

We applied a 1H-NMR metabolomics approach to investigate the altered metabolic pattern in sera from patients with asthma and sought to identify the mechanism underlying asthma and potential biomarkers.

Method

A global profile of sera from patients with asthma (n = 39) and controls (n = 26) was generated using 1H-NMR spectroscopy coupled with multivariate statistical analysis. Endogenous metabolites in serum were rapidly measured using the target-profiling procedure.

Results

Multivariate statistical analysis showed a clear distinction between patients with asthma and healthy subjects. Sera of asthma patients were characterized by increased levels of methionine, glutamine, and histidine and by decreased levels of formate, methanol, acetate, choline, O-phosphocholine, arginine, and glucose. The metabolites detected in the sera of patients with asthma are involved in hypermethylation, response to hypoxia, and immune reaction. Furthermore, the levels of serum metabolites from patients with asthma correlated with asthma severity; in particular, lipid metabolism was altered in patients with lower forced expiratory volume in 1 s percentage (FEV1%) predicted values. In addition, potential biomarkers showed strong predictive power in ROC analysis, and the presence of asthma in external validation models was predicted with high accuracy (90.9% for asthma and 100% for control subjects).

Conclusion & Clinical Relevance

These data showed that 1H-NMR-based metabolite profiling of serum may be useful for the effective diagnosis of asthma and a further understanding of its pathogenesis.

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