Smokers with COPD Show a Shift in Energy and Nitrogen Metabolism at Rest and During Exercise

Int J Chron Obstruct Pulmon Dis. 2020 Jan 6:15:1-13. doi: 10.2147/COPD.S217474. eCollection 2020.

Abstract

Purpose: There is an ongoing demand for easily accessible biomarkers that reflect the physiological and pathophysiological mechanisms of COPD. To test if an exercise challenge could help to identify clinically relevant metabolic biomarkers in COPD.

Patients and methods: We performed two constant-load exercise challenges separated by 4 weeks including smokers with COPD (n=23/19) and sex- and age-matched healthy smokers (n=23/20). Two hours after a standardized meal venous blood samples were obtained before, 5 mins after the start, at the end of submaximal exercise, and following a recovery of 20 mins. Data analysis was performed using mixed- effects model, with the metabolite level as a function of disease, time point and interaction terms and using each individual's resting level as reference.

Results: Exercise duration was longer in healthy smokers but lactate levels were comparable between groups at all four time points. Glucose levels were increased in COPD. Glutamine was lower, while glutamate and arginine were higher in COPD. Branched-chain amino acids showed a stronger decline during exercise in healthy smokers. Carnitine and the acyl-carnitines C16 and C18:1 were increased in COPD. These metabolite levels and changes were reproducible in the second challenge.

Conclusion: Higher serum glucose, evidence for impaired utilization of amino acids during exercise and a shift of energy metabolism to enhanced consumption of lipids could be early signs for a developing metabolic syndrome in COPD. In COPD patients, deviations of energy and nitrogen metabolism are amplified by an exercise challenge.

Keywords: airway inflammation; biomarker; targeted metabolomics.

MeSH terms

  • Adult
  • Aged
  • Amino Acids / blood*
  • Asymptomatic Diseases
  • Bicycling
  • Biomarkers / blood
  • Blood Glucose / metabolism
  • Case-Control Studies
  • Energy Metabolism*
  • Exercise Test
  • Female
  • Humans
  • Lipids / blood
  • Male
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / diagnosis*
  • Metabolic Syndrome / physiopathology
  • Metabolomics
  • Middle Aged
  • Nitrogen / metabolism*
  • Predictive Value of Tests
  • Pulmonary Disease, Chronic Obstructive / blood
  • Pulmonary Disease, Chronic Obstructive / diagnosis*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Smokers*
  • Smoking / adverse effects*
  • Smoking / blood
  • Smoking / physiopathology

Substances

  • Amino Acids
  • Biomarkers
  • Blood Glucose
  • Lipids
  • Nitrogen

Grants and funding

Fraunhofer has received a research grant for conducting the study from Nycomed GmbH. Nycomed employees participated in study design, and in data analysis (SR, CS). OH, DSD, JMH were supported by the German Center for Lung Research.