Oxidative Stress and Pteridines in Pediatric Asthma: Relationship to Exhaled Nitric Oxide

Fractional exhaled nitric oxide (FeNO) is a useful marker of airway inflammation in asthmatics. Nitric oxide synthase (NOS) requires tetrahydrobiopterin as a cofactor and produces superoxide during NO generation. Therefore, we investigated the relationship of FeNO to pteridine biosynthesis and oxidative stress in pediatric asthma patients. We recruited 67 asthmatic children for FeNO measurement and examined neopterin, biopterin, and Diacron-reactive oxygen metabolites (d-ROMs) as an oxidative stress marker in both summer and winter. Although d-ROMs levels did not show significant correlation with FeNO levels in summer, d-ROMs and FeNO were positively correlated in winter (p < 0.05). Both neopterin and biopterin levels in the blood tended to be lower in patients who showed higher FeNO. Multivariate analysis revealed that increased IgE levels correlated with increased FeNO (p < 0.01) and decreased neopterin (p < 0.05) levels. This data supports a mechanism by which decreased levels of pteridines promote reactive oxygen species production upon NO generation, resulting in airway injury in asthmatic patients. Correlation with IgE level indicates that Th2-mediated allergic inflammation is involved in this process.