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

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.