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Metabolic profiling detects biomarkers of protein degradation in COPD patients

Research output: Contribution to journalArticle

  • B K Ubhi
  • J H Riley
  • P A Shaw
  • D A Lomas
  • R Tal-Singer
  • W Macnee
  • J L Griffin
  • S C Connor

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Original languageEnglish
JournalEuropean Respiratory Journal
Volume40
Issue number2
DOIs
Publication statusPublished - 1 Aug 2011

Abstract

There is a paucity of well-validated biomarkers for chronic obstructive pulmonary disease (COPD). Metabolomics, which identifies novel biomarkers, was applied to a well-defined COPD patient cohort from the ECLIPSE study. Results were correlated with accepted biomarkers of disease.Baseline serum from controls (n=66) and GOLD II (n=70), III (n=64) and IV (n=44) COPD patients were analysed by NMR-based metabolomics. LC-MS/MS targeted metabolomics was used to confirm amino acid changes detected by NMR. Data were correlated with body composition, emphysema and systemic inflammation.Open profiling metabolomics identified decreased lipoproteins (VLDL/chymicrons; LDL) and N, N-dimethylglycine and increased glutamine, phenylalanine, 3-methylhistidine and ketone bodies in COPD patients with decreased branched chain amino acids (BCAAs) also observed in GOLD IV patients. BCAAs, their degradation products, 3-methylhistidine, ketone bodies and triglycerides were correlated negatively with cachexia and positively with systemic inflammation. Emphysema patients also had decreased serum creatine, glycine and N, N-dimethylglycine. LC-MS/MS confirmed NMR findings relating to BCAAs, glutamine and 3-methylhistidine in GOLD IV patients.NMR-based metabolomics characterised COPD patients based on systemic effects and lung function parameters. Increased protein turnover occurred in all COPD patients with increased protein degradation in individuals with emphysema and cachexia.

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