L-Arginine Pathway in COPD Patients with Acute Exacerbation: A New Potential Biomarker

Abstract

Background: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) remains a major cause of mortality. Clinical criteria of AECOPD are subjective. Biomarkers for AECOPD may aid in the initiation of early treatment. Increased production of asymmetric and symmetric dimethylarginine (ADMA, SDMA) is related to hypoxia. In COPD, a rise in ADMA results in a shift of L-arginine breakdown, contributing to airway obstruction. We aimed to compare serum levels of ADMA, SDMA and L-arginine in patients with and without AECOPD.

Methods: L-arginine metabolites quantified by high-performance liquid chromatography in venous blood samples and partial capillary oxygen pressure were prospectively investigated in 32 patients with COPD, 12 with AECOPD and 30 healthy subjects.

Results: Both ADMA and SDMA were significantly higher in AECOPD compared to stable COPD (p = 0.004 and p < 0.001, respectively). Oxygen content in capillaries correlated with serum ADMA concentration. However, the concentration of L-arginine was not different between AECOPD and stable COPD. Both ADMA and SDMA separated AECOPD with high sensitivity and specificity (AUC: 0.81, p = 0.001; AUC: 0.91, p < 0.001, respectively). A cut-off value ≥0.57 for SDMA was an independent variable to confirm AECOPD in a regression model (OR: 1.632, p = 0.001). All markers were significantly higher in the sera of both patient groups compared to the controls (p < 0.05, respectively).

Conclusions: COPD is associated with elevated L-arginine, ADMA and SDMA serum levels. In patients with AECOPD, production of ADMA and SDMA are more pronounced presumably due to more severe hypoxic insult. Methylated arginine derivatives in the sera may help early recognition of AECOPD.

Keywords:

• asymmetric and symmetric dimethylarginine
• chronic obstructive pulmonary disease
• L-arginine

Acknowledgments

The authors thank Elise Steen for copyediting the revised manuscript.

Funding

This study was supported by a grant from University of Pecs AOK-KA- 34039/10-17 to T. Molnar.

Declaration of Interest Statement

Author contributions: TM had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. LN and SK contributed substantially to study design, measurement of the biomarkers and interpretation of the results. IR, VS, BI contributed substantially to recruitment of patients, blood sampling and study design. TM, LB, IR, ZI and IH contributed substantially to data analysis and interpretation, and the writing of the manuscript. TM takes responsibility for the content of the manuscript, including the data and analysis.