RT Journal Article
SR Electronic
T1 Metabolic profiling detects biomarkers of protein degradation in COPD patients
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP erj01124-2011
DO 10.1183/09031936.00112411
A1 B.K. Ubhi
A1 J.H. Riley
A1 P.A. Shaw
A1 D.A. Lomas
A1 R. Tal-Singer
A1 W. MacNee
A1 J.L. Griffin
A1 S.C. Connor
YR 2012
UL http://erj.ersjournals.com/content/early/2011/12/16/09031936.00112411.abstract
AB 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.