Positive correlation of airway resistance and serum asymmetric dimethylarginine level in COPD patients with systemic markers of low-grade inflammation

Gabor Tajti,1,2 Rudolf Gesztelyi,3 Krisztian Pak,3 Csaba Papp,1 Sandor Keki,4 Magdolna Emma Szilasi,2 Angela Mikaczo,2 Andrea Fodor,2 Maria Szilasi,2 Judit Zsuga1 1Department of Health Systems Management and Quality Management for Health Care, Faculty of Public Health, 2Department of Pulmonology, Faculty of Medicine, 3Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, 4Department of Applied Chemistry, Faculty of Science and Technology, University of Debrecen, Debrecen, Hungary 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 Raw showed 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 Raw in the final model. Positive correlation of Raw with 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. Keywords: ADMA, airway resistance, nitric oxide, SGRQ, whole-body plethysmography