Positive correlation of airway resistance and serum asymmetric dimethylarginine (ADMA) in bronchial asthma patients lacking evidence for systemic inflammation

Gabor Tajti; Csaba Papp; Laszlo Kardos; Sandor Keki; Krisztian Pak; Magdolna Emma Szilasi; Rudolf Gesztelyi; Angela Mikaczo; Andrea Fodor; Maria Szilasi; Judit Zsuga

doi:10.1186/s13223-017-0226-5

Positive correlation of airway resistance and serum asymmetric dimethylarginine (ADMA) in bronchial asthma patients lacking evidence for systemic inflammation

Allergy Asthma Clin Immunol. 2018 Jan 3:14:2. doi: 10.1186/s13223-017-0226-5. eCollection 2018.

Authors

Affiliations

¹ Department of Health Systems Management and Quality Management for Health Care, Faculty of Public Health, University of Debrecen, Nagyerdei krt. 98, Debrecen, 4032 Hungary.
² Institute of Clinical Pharmacology, Infectious Diseases and Allergology, Kenezy Gyula Teaching County Hospital and Outpatient Clinic, Bartok Bela ut 2-26, Debrecen, 4031 Hungary.
³ Department of Applied Chemistry, Faculty of Science and Technology, University of Debrecen, Egyetem ter 1, Debrecen, 4032 Hungary.
⁴ Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, Debrecen, 4032 Hungary.
⁵ Department of Pulmonology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, Debrecen, 4032 Hungary.

Abstract

Background: Contribution of nitric-oxide (NO) pathway to the pathogenesis of bronchial asthma (asthma) is ambiguous as NO may confer both protective and detrimental effects depending on the NO synthase (NOS) isoforms, tissue compartments and underlying pathological conditions (e.g. systemic inflammation). Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor and uncoupler of NOS with distinct selectivity for NOS isoforms. In a cross-sectional study, we assessed whether ADMA is an independent predictor of airway resistance (R_aw) in therapy-controlled asthma.

Methods: 154 therapy-controlled asthma patients were recruited. ADMA, symmetric dimethylarginine and arginine were quantitated by HPLC with fluorescent detection. Pulmonary function test was done using whole-body plethysmography, quality of life via St. George's Respiratory questionnaire (SGRQ). Multiple linear regression was used to identify independent determinants of R_aw. The final model was stratified based on therapy control.

Results: Evidence for systemic inflammation indicated by CRP and procalcitonin was lacking in our sample. Log R_aw showed significant positive correlation with log ADMA in the whole data set and well-controlled but not in the not well-controlled stratum (Spearman correlation coefficients: 0.27, p < 0.001; 0.30, p < 0.001; 0.12, p = 0.51 respectively). This relationship remained significant after adjusting for confounders by multiple linear regression (β = 0.22, CI 0.054, 0.383 p = 0.01). FEF 25-75% % predicted and SGRQ Total score showed significant negative while SGRQ Activity score showed significant positive correlation with R_aw in the final model.

Conclusions: Positive correlation between R_aw and ADMA in the absence of systemic inflammation implies that higher ADMA has detrimental effect on NO homeostasis and can contribute to a poor outcome in asthma.

Keywords: ADMA; Airway resistance; Bronchial asthma; SGRQ; Whole-body plethysmography.