ASYMMETRIC DIMETHYLARGININE (ADMA) IN EXHALED BREATH CONDENSATE AND SERUM OF ASTHMATIC CHILDREN.

BACKGROUND. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor and uncoupler of nitric oxide synthase. By promoting the formation of peroxynitrite, ADMA is believed to contribute to several aspects of asthma pathogenesis, i.e. airway inflammation, oxidative stress, bronchial hyperresponsiveness and collagen deposition. The aim of the present study was to compare this mediator in asthmatic and healthy children using the completely non-invasive exhaled breath condensate (EBC) technique. METHODS. We recruited 77 asthmatic children (5-16y) and 65 healthy children (5-15y) who underwent EBC collection and spirometry. Serum ADMA levels and FENO levels were measured on the same day in a subgroup of asthmatic children. EBC was collected using the Turbo-Deccs (Medivac, Parma, Italy). ADMA levels were measured using the Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry(UPLC-MS/MS) technique. RESULTS. ADMA could be detected in the EBC of 71 asthmatic and 64 healthy subjects. ADMA levels in the EBC of asthmatic children were significantly higher than in the healthy controls (median 0.12[IQR 0.05-0.3] vs 0.07[0.05-0.12], p=0.017), while no difference emerged between the asthmatic children who were or were not on inhaled steroid treatment. No correlation was found between serum and EBC ADMA levels (p>0.5). CONCLUSIONS. We measured ADMA in EBC by UPLC-MS/MS, a reference analytical technique. Higher ADMA levels were found in asthmatic children, supporting a role for this mediator in asthma pathogenesis. This oxidative stress-related mediator also seems to be scarcely affected by steroid therapy. We speculate that ADMA might be a target for new therapeutic strategies designed to control oxidative stress in asthma.