Circulating and exhaled markers of nitric oxide and antioxidant activity after smoking.

and Antioxidant Activity After Smoking To the Editor: We read with interest the article by Tsuchiya et al1 showing that smoking a single cigarette results in a significant acute reduction in plasma nitrite/nitrate (NOx) and antioxidant defenses. The pathway by which cigarette smoke inhalation causes systemic oxidant stress presumably begins within the lungs, but until recently, simple methods of detecting inflammatory markers from the respiratory tract were not available. Techniques such as bronchioalveolar lavage and induced sputum are invasive and unsuitable for investigating the effect of an acute stimulus. Measurement of exhaled NO concentrations have yielded contradictory results. Exhaled breath condensate (EBC) collected by cooling exhaled air is, however, noninvasive and does not influence airway inflammation, making it ideally suited to this purpose.2 We have recently investigated the effects of smoking on systemic and EBC markers of NO synthesis and antioxidant status. In 12 otherwise healthy smokers (5 men, age 22 3.8 years), NOx and glutathione were determined in both serum and EBC immediately before and 45 and 225 minutes after smoking 2 cigarettes. The same markers were measured in 12 healthy non-smokers (6 men, 21 0.7 years) to assess the effects of habitual cigarette smoking. At baseline, smokers had an elevated glutathione concentration in serum and in EBC compared with non-smokers (serum: 5.6 0.9 mol/L versus 3.2 0.3 mol/L, P 0.05; EBC: 40.0 0.8 mol/L versus 12.5 0.8 mol/L, P 0.05). Forty-five minutes after smoking, glutathione was significantly reduced in both serum and EBC (serum: 2.2 0.7 mol/L, P 0.01; EBC: 20.0 0.5 mol/L, P 0.05). Serum NOx was similarly reduced after smoking (39.0 0.7 mol/L versus 32.5 0.7 mol/L, P 0.01), whereas EBC NOx remained unchanged. Serum and EBC glutathione and serum NOx returned to near baseline concentration by 225 minutes. Our findings suggest that the acute oxidant effects of smoking are followed by depletion of local as well as systemic antioxidants, and that long-term smoking may lead to upregulation of the important antioxidant compound glutathione.3 Although we did not demonstrate a change in EBC NOx at 45 or 225 minutes after smoking, the concentration of exhaled nitric oxide metabolites is difficult to interpret. Exhaled NOx is predominantly derived from airway epithelial and inflammatory cells rather than the pulmonary circulation.4 We propose that EBC is a useful tool to investigate the mechanisms by which pulmonary insults contribute to cardiovascular morbidity and mortality. The systemic oxidative stress caused by smoking seems to occur in association with pulmonary antioxidant consumption. The pulmonary contribution to systemic inflammation and oxidant stress after smoking deserves further investigation.