Role of endogenous nitric oxide in exercise-induced airway narrowing in patients with bronchial asthma

BACKGROUND: Increased amounts of nitric oxide (NO) in expired air and induced sputum have been found in asthmatic patients, and the role of excessively produced NO in the pathogenesis of bronchial asthma is under active investigation. OBJECTIVE: This study was designed to investigate the involvement of endogenous NO in exercise-induced bronchoconstriction (EIB) in asthmatic patients by using the sputum induction method. METHODS: The concentration of NO derivatives and inflammatory indices in induced sputum were examined in 18 asthmatic subjects and 10 normal control subjects. All asthmatic subjects performed an exercise test for 6 minutes. For 8 weeks after the first exercise testing, 400 microg of beclomethasone dipropionate twice daily was administered for asthmatic subjects with EIB, and the exercise testing and sputum induction were repeated in these patients. RESULTS: The concentration of NO derivatives in induced sputum was significantly higher in 9 asthmatic subjects with EIB (1580 +/- 280 micromol/L) than in 9 asthmatic subjects without EIB (1130 +/- 210 micromol/L) and normal control subjects (510 +/- 150 micromol/L). Moreover, there was a significant correlation between the concentration of NO derivatives and the percentage of maximal fall in FEV(1) (r = 0.569, P =.019). The concentration of NO derivatives was also more closely correlated with the area under the curve of the percentage fall in FEV(1) plotted against time for 30 minutes (AUC(0-30); r = 0.812, P <.001). After treatment with inhaled beclomethasone dipropionate in asthmatic subjects with EIB, there was a significant decrease in the concentration of NO derivatives in induced sputum. The change in the concentration of NO derivatives was significantly correlated with the change in the AUC(0-30) (r = 0.896, P =.0114) but not with the change in the percentage of maximal fall in FEV(1). CONCLUSION: These findings suggest that excessive production of NO is associated with EIB in patients with asthma and contributes to the prolonged airway narrowing phase rather than to the maximal airway narrowing evoked by exercise.