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

Istvan Ruzsics, Lajos Nagy, S. Kéki, Veronika Sarosi, Balazs Illes, Zsolt Illes, I. Horváth, L. Bogár, Tihamer Molnar

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
JournalCOPD: Journal of Chronic Obstructive Pulmonary Disease
DOIs
Publication statusAccepted/In press - Oct 1 2015

Fingerprint

Chronic Obstructive Pulmonary Disease
Arginine
Biomarkers
Serum
Area Under Curve
Oxygen
Airway Obstruction
Healthy Volunteers

Keywords

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

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

L-Arginine Pathway in COPD Patients with Acute Exacerbation : A New Potential Biomarker. / Ruzsics, Istvan; Nagy, Lajos; Kéki, S.; Sarosi, Veronika; Illes, Balazs; Illes, Zsolt; Horváth, I.; Bogár, L.; Molnar, Tihamer.

In: COPD: Journal of Chronic Obstructive Pulmonary Disease, 01.10.2015.

Research output: Contribution to journalArticle

@article{4828d0ff0c814ec591163110de99ab6f,
title = "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",
author = "Istvan Ruzsics and Lajos Nagy and S. K{\'e}ki and Veronika Sarosi and Balazs Illes and Zsolt Illes and I. Horv{\'a}th and L. Bog{\'a}r and Tihamer Molnar",
year = "2015",
month = "10",
day = "1",
doi = "10.3109/15412555.2015.1045973",
language = "English",
journal = "COPD: Journal of Chronic Obstructive Pulmonary Disease",
issn = "1541-2555",
publisher = "Informa Healthcare",

}

TY - JOUR

T1 - L-Arginine Pathway in COPD Patients with Acute Exacerbation

T2 - A New Potential Biomarker

AU - Ruzsics, Istvan

AU - Nagy, Lajos

AU - Kéki, S.

AU - Sarosi, Veronika

AU - Illes, Balazs

AU - Illes, Zsolt

AU - Horváth, I.

AU - Bogár, L.

AU - Molnar, Tihamer

PY - 2015/10/1

Y1 - 2015/10/1

N2 - 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.

AB - 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.

KW - asymmetric and symmetric dimethylarginine

KW - chronic obstructive pulmonary disease

KW - L-arginine

UR - http://www.scopus.com/inward/record.url?scp=84945338867&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84945338867&partnerID=8YFLogxK

U2 - 10.3109/15412555.2015.1045973

DO - 10.3109/15412555.2015.1045973

M3 - Article

C2 - 26514682

AN - SCOPUS:84945338867

JO - COPD: Journal of Chronic Obstructive Pulmonary Disease

JF - COPD: Journal of Chronic Obstructive Pulmonary Disease

SN - 1541-2555

ER -