Effects of nitrogen dioxide exposure and ascorbic acid supplementation on exhaled nitric oxide in healthy human subjects

Background-Nitric oxide (NO) is detectable in the exhaled breath, is involved in airway defence and inflammation, and probably modulates bronchial smooth muscle tone. Given the sensitivity of nitrogen oxides to local redox conditions, we postulated that exposure to oxidant or antioxidant compounds could alter concentrations of NO in the exhaled breath (eNO). We assessed the effect of nitrogen dioxide (NO2) and ascorbic acid exposure on eNO in healthy human subjects. Methods-Ten healthy subjects were randomised to undergo a 20 minute single blind exposure to NO2 (1.5 parts per million) or medical air in a crossover fashion. Exhaled NO and pulmonary function were measured before and for 3 hours after exposure. In a separate double blind crossover study 20 healthy subjects received ascorbic acid 500 mg twice daily or placebo for 2 weeks with a 6 week interim washout. Serum ascorbic acid levels and eNO were measured before and after each supplementation phase. Results-NO2 induced a decrease of 0.62 (95% CI 0.32 to 0.92) ppb in the mean post-exposure eNO (p <0.01) with no change in forced expiratory volume in 1 second (FEV,). Oral supplementation with ascorbic acid increased the mean serum ascorbic acid concentration by 7.4 (95% CI 5.1 to 9.7) mug/ml (63%) but did not alter eNO. Conclusions-NO2 exposure causes a decrease in eNO, an effect which may be mediated through changes in epithelial lining fluid redox state or through a direct effect on epithelial cells. In contrast, ascorbic acid does not appear to play a significant role in the metabolism of NO in the epithelial lining fluid.