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.
authors.affiliation: a 1 Department of Pulmonology, University of Pecs , Pecs , Hungary.
authors.forename: Istvan
authors.initials: I
authors.lastname: Ruzsics
authors.affiliation: b 2 Department of Applied Chemistry, University of Debrecen , Debrecen , Hungary.
authors.forename: Lajos
authors.initials: L
authors.lastname: Nagy
authors.affiliation: b 2 Department of Applied Chemistry, University of Debrecen , Debrecen , Hungary.
authors.forename: Sandor
authors.initials: S
authors.lastname: Keki
authors.affiliation: a 1 Department of Pulmonology, University of Pecs , Pecs , Hungary.
authors.forename: Veronika
authors.initials: V
authors.lastname: Sarosi
authors.affiliation: a 1 Department of Pulmonology, University of Pecs , Pecs , Hungary.
authors.forename: Balazs
authors.initials: B
authors.lastname: Illes
authors.affiliation: c 3 Department of Neurology, Odense University Hospital , Odense , Denmark.|d 4 Institute of Clinical Research, University of Southern Denmark , Odense , Denmark.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Illes
authors.affiliation: e 5 Department of Pulmonology, Semmelweis University and National Koranyi Institute for Pulmonology , Budapest , Hungary.
authors.forename: Ildiko
authors.initials: I
authors.lastname: Horvath
authors.affiliation: f 6 Department of Anesthesiology and Intensive Care, University of Pecs , Pecs , Hungary.
authors.forename: Lajos
authors.initials: L
authors.lastname: Bogar
authors.affiliation: f 6 Department of Anesthesiology and Intensive Care, University of Pecs , Pecs , Hungary.
authors.forename: Tihamer
authors.initials: T
authors.lastname: Molnar
mesh_terms: D001120:Arginine / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005540:Forced Expiratory Flow Rates; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D012720:Severity of Illness Index; D053719:Tandem Mass Spectrometry; D013997:Time Factors
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein; D001120:Arginine
keywords: L-arginine; asymmetric and symmetric dimethylarginine; chronic obstructive pulmonary disease