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 ((1)H NMR). Liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used to confirm
amino acid changes detected by (1)H NMR. Data were correlated with body composition,
emphysema and systemic
inflammation. (1)H 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 (1)H 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.