title: Positive correlation of airway resistance and serum asymmetric dimethylarginine level in COPD patients with systemic markers of low-grade inflammation.
abstract: The major feature of COPD is a progressive airflow limitation caused by chronic airway inflammation and consequent airway remodeling. Modified arginase and nitric oxide synthase (NOS) pathways are presumed to contribute to the inflammation and fibrosis. Asymmetric dimethylarginine (ADMA) may shunt L-arginine from the NOS pathway to the arginase one by uncoupling and competitive inhibition of NOS and by enhancing arginase activity. To attest the interplay of these pathways, the relationship between ADMA and airflow limitation, described by airway resistance (Raw), was investigated in a cohort of COPD patients. Every COPD patient willing to give consent to participate (n=74) was included. Case history, laboratory parameters, serum arginine and ADMA, pulmonary function (whole-body plethysmography), and disease-specific quality of life (St George's Respiratory Questionnaire) were determined. Multiple linear regression was used to identify independent determinants of Raw. The final multiple model was stratified based on symptom control. The log Rawshowed significant positive correlation with log ADMA in the whole sample (Pearson's correlation coefficient: 0.25,P=0.03). This association remained significant after adjusting for confounders in the whole data set (β: 0.42; confidence interval [CI]: 0.06, 0.77;P=0.022) and in the worse-controlled stratum (β: 0.84; CI: 0.25, 1.43;P=0.007). Percent predicted value of forced expiratory flow between 25% and 75% of forced vital capacity showed that significant negative, elevated C-reactive protein exhibited significant positive relationship with Rawin the final model. Positive correlation of Rawwith ADMA in COPD patients showing evidence of a systemic low-grade inflammation implies that ADMA contributes to the progression of COPD, probably by shunting L-arginine from the NOS pathway to the arginase one.
authors.affiliation: Department of Health Systems Management and Quality Management for Health Care, Faculty of Public Health; Department of Pulmonology, Faculty of Medicine.
authors.forename: Gabor
authors.initials: G
authors.lastname: Tajti
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Gesztelyi
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine.
authors.forename: Krisztian
authors.initials: K
authors.lastname: Pak
authors.affiliation: Department of Health Systems Management and Quality Management for Health Care, Faculty of Public Health.
authors.forename: Csaba
authors.initials: C
authors.lastname: Papp
authors.affiliation: Department of Applied Chemistry, Faculty of Science and Technology, University of Debrecen, Debrecen, Hungary.
authors.forename: Sandor
authors.initials: S
authors.lastname: Keki
authors.affiliation: Department of Pulmonology, Faculty of Medicine.
authors.forename: Magdolna Emma
authors.initials: ME
authors.lastname: Szilasi
authors.affiliation: Department of Pulmonology, Faculty of Medicine.
authors.forename: Angela
authors.initials: A
authors.lastname: Mikaczo
authors.affiliation: Department of Pulmonology, Faculty of Medicine.
authors.forename: Andrea
authors.initials: A
authors.lastname: Fodor
authors.affiliation: Department of Pulmonology, Faculty of Medicine.
authors.forename: Maria
authors.initials: M
authors.lastname: Szilasi
authors.affiliation: Department of Health Systems Management and Quality Management for Health Care, Faculty of Public Health.
authors.forename: Judit
authors.initials: J
authors.lastname: Zsuga
mesh_terms: D000368:Aged; D000403:Airway Resistance / Q000187:drug effects; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001993:Bronchodilator Agents / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000032:analysis*; D016009:Chi-Square Distribution; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D016014:Linear Models; D008168:Lung / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D008450:Maximal Midexpiratory Flow Rate; D008875:Middle Aged; D010993:Plethysmography, Whole Body; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D011795:Surveys and Questionnaires
chemical_list: D015415:Biomarkers; D001993:Bronchodilator Agents; D018836:Inflammation Mediators; C018524:N,N-dimethylarginine; D002097:C-Reactive Protein; D001120:Arginine
keywords: ADMA; SGRQ; airway resistance; nitric oxide; whole-body plethysmography