PT  - JOURNAL ARTICLE
AU  - Baljit K. Ubhi
AU  - John H. Riley
AU  - Paul A. Shaw
AU  - David A. Lomas
AU  - Ruth Tal-Singer
AU  - William MacNee
AU  - Julian L. Griffin
AU  - Susan C. Connor
TI  - Metabolic profiling detects biomarkers of protein degradation in COPD patients
AID  - 10.1183/09031936.00112411
DP  - 2012 Aug 01
TA  - European Respiratory Journal
PG  - 345--355
VI  - 40
IP  - 2
4099  - http://erj.ersjournals.com/content/40/2/345.short
4100  - http://erj.ersjournals.com/content/40/2/345.full
SO  - Eur Respir J2012 Aug 01; 40
AB  - There is a paucity of biomarkers for chronic obstructive pulmonary disease (COPD). Metabolomics were applied to a defined COPD patient cohort from the ECLIPSE study (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points). Results were correlated with accepted biomarkers for the disease. Baseline control serum (n=66) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II (n=70), III (n=64) and IV (n=44) COPD patients were analysed by proton nuclear magnetic resonance (1H NMR). Liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used to confirm amino acid changes detected by 1H NMR. Data were correlated with body composition, emphysema and systemic inflammation. 1H NMR identified decreased lipoproteins, N,N-dimethylglycine, and increased glutamine, phenylalanine, 3-methylhistidine and ketone bodies in COPD patients with decreased branched-chain amino acids (BCAAs) observed in GOLD stage 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 displayed decreased serum creatine, glycine and N,N-dimethylglycine. LC-MS/MS confirmed 1H NMR findings relating to BCAAs, glutamine and 3-methylhistidine in GOLD stage 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.