CHRONIC OBSTRUCTIVE PULMONARY DISEASE Imbalance between levels of nitrogen oxides and peroxynitrite inhibitory activity in chronic obstructive pulmonary disease

Background: The prevalent theory concerning the pathogenesis of chronic obstructive pulmonary disease (COPD) is of an imbalance between oxidants and antioxidants in the lung. It has recently been reported that the production of peroxynitrite, an extremely potent oxidant, is increased in the airways of patients with COPD. A study was undertaken of the imbalance between the levels of nitrogen oxides and antioxidant activity against peroxynitrite in the airways of patients with COPD. Methods: Sputum induction was performed in 30 patients with COPD and 15 normal control subjects. Levels of nitrogen oxides, percentage of neutrophils, and interleukin 8 (IL-8) levels were measured in sputum samples, and peroxynitrite inhibitory activity was assayed by monitoring rhodamine formation. Results: Nitrite and nitrate levels in induced sputum were significantly higher in patients with COPD than in normal controls (949 (133) μM v 621 (89) μM, p<0.001). In contrast, peroxynitrite inhibitory activity in induced sputum was significantly lower in patients with COPD than in normal controls (47.4 (12.7)% v 92.9 (3.9)%, p<0.001). There was a negative correlation between nitrite and nitrate levels and peroxynitrite inhibitory activity in induced sputum (r=–0.775, p<0.001). Peroxynitrite inhibitory activity was also significantly correlated with forced expiratory volume in 1 second (FEV1) % predicted (r=0.539, p=0.004), FEV1/FVC (r=0.512, p=0.006), and carbon monoxide transfer factor (TLCO) (r=0.486, p=0.009). Moreover, there was a significant negative correlation between peroxynitrite inhibitory activity and the degree of neutrophilic inflammation (percentage of neutrophils: r=–0.754, p<0.001; IL-8 levels: r=–0.497, p=0.007). Conclusions: Reduced peroxynitrite inhibitory activity and increased levels of nitrogen oxides are found in induced sputum from patients with COPD. An imbalance in nitrogen oxides and antioxidant defence may contribute to the pathogenesis of COPD.