Istvan Ruzsics1, Lajos Nagy2, Sandor Keki2, Veronika Sarosi1, Balazs Illes1, Zsolt Illes3,4, Ildiko Horvath5, Lajos Bogar6, Tihamer Molnar6. 1. a 1 Department of Pulmonology, University of Pecs , Pecs , Hungary. 2. b 2 Department of Applied Chemistry, University of Debrecen , Debrecen , Hungary. 3. c 3 Department of Neurology, Odense University Hospital , Odense , Denmark. 4. d 4 Institute of Clinical Research, University of Southern Denmark , Odense , Denmark. 5. e 5 Department of Pulmonology, Semmelweis University and National Koranyi Institute for Pulmonology , Budapest , Hungary. 6. f 6 Department of Anesthesiology and Intensive Care, University of Pecs , Pecs , Hungary.
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.
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.
Entities:
Keywords:
L-arginine; asymmetric and symmetric dimethylarginine; chronic obstructive pulmonary disease
Authors: Alaadin Vögeli; Manuel Ottiger; Marc A Meier; Christian Steuer; Luca Bernasconi; Andreas Huber; Mirjam Christ-Crain; Christoph Henzen; Claus Hoess; Robert Thomann; Werner Zimmerli; Beat Mueller; Philipp Schuetz Journal: Lung Date: 2017-08-29 Impact factor: 2.584
Authors: Shama Naz; Johan Kolmert; Mingxing Yang; Stacey N Reinke; Muhammad Anas Kamleh; Stuart Snowden; Tina Heyder; Bettina Levänen; David J Erle; C Magnus Sköld; Åsa M Wheelock; Craig E Wheelock Journal: Eur Respir J Date: 2017-06-22 Impact factor: 16.671