Study objectives: We recently found that peroxynitrite inhibitory activity in induced sputum was significantly lower in asthmatic patients than in normal control subjects. Current guidelines recommend inhaled corticosteroids as first-line control therapy in asthma. Therefore, this study was designed to examine the effect of inhaled beclomethasone dipropionate (BDP) on peroxynitrite inhibitory activity in induced sputum from asthmatic patients.
Design: Interventional study.
Setting: University hospital.
Patients: Twenty-one asthmatic patients and 10 age-matched, normal control subjects.
Interventions: Inflammatory indexes in induced sputum were examined in all study subjects, and peroxynitrite inhibitory activity was also assayed by monitoring rhodamine formation. For 8 weeks after the first sputum induction, BDP 400 μg bid, was administered to all asthmatic patients and sputum induction was repeated.
Measurements and results: Nitrite and nitrate levels in induced sputum were significantly higher in asthmatic patients (1,121 μmol/L [SD, 205 μmol/L], p < 0.0001) than in normal control subjects (642 μmol/L [SD, 137 μmol/L]). In contrast, peroxynitrite inhibitory activity in induced sputum was significantly lower in asthmatic patients (50.0% [SD, 25.7%], p < 0.0001) than in normal control subjects (93.0% [SD, 3.6%]). After 8 weeks of BDP therapy, nitrite and nitrate levels were significantly decreased (847 μmol/L [SD, 143 μmol/L], p < 0.0001) and peroxynitrite inhibitory activity was increased (73.9% [SD, 19.2%], p = 0.0005). Moreover, the increase in peroxynitrite inhibitory activity from before to after BDP therapy was significantly correlated with decrease in nitrite and nitrate levels (r = 0.79, p = 0.0004). We also found the significant relationship between increase in peroxynitrite inhibitory activity in induced sputum and increase in FEV1 percentage of predicted after BDP therapy (r = 0.68, p = 0.0023).
Conclusions: Large amounts of peroxynitrite, which are exaggerated in acute asthma attacks, might overwhelm endogenous antioxidant defenses. However, inhaled corticosteroid therapy enhanced antioxidant activity against peroxynitrite, and therefore might reduce the susceptibility to peroxynitrite-induced injury in asthmatic airways.