Altered serum metabolomics in COPD: analysis of the SPIROMICS cohort

Background: Little is known about the role of the metabolome in COPD pathogenesis. Aims: To identify metabolic alterations associated with airflow obstruction in smokers. Methods: We analyzed serum samples of 157 smokers by quantitative nuclear magnetic resonance (NMR) spectroscopy. Airflow obstruction (post-bronchodilator FEV1/FVC < 0.7) was staged according to GOLD guidelines. GOLD 0 was defined as post-bronchodilator FEV1/FVC > 0.7 and FEV1 > 80% predicted. We tested associations between metabolite concentrations and FEV1 % predicted using multivariate regression analyses adjusted for age, sex, current smoking, body mass index (BMI) and study site. Results: Participants (mean age 53.7 years, 50.3% women, 56.1% current smokers, BMI 27.7 kg/m2) had a mean FEV1 of 78.7% predicted. Twenty-nine metabolites (16 amino acids) were identified by NMR spectral analysis using Chenomx. Overall, 26 of the metabolites were lower in GOLD 3-4 subjects compared to GOLD 0-2 subjects. Multivariate analyses showed a significant positive relationship between the concentrations of 4 metabolites and FEV1% predicted (figure): tryptophan (p=0.002), histidine (p=0.019), valine (p=0.026) and leucine (p=0.034). Conclusions: More severe airflow obstruction is associated with downregulation of serum metabolites in smokers.