High doses of N-acetylcysteine alone or in combination with inhaled corticosteroids and oxidative stress in patients with COPD

Background: Oxidant/antioxidant interactions are known to be important processes in the pathogenesis of COPD. We aimed to evaluate the effects of 6-month oral N-acetylcysteine (NAC) treatment 600 mg twice daily alone or in combination with inhaled corticosteroids (ICS) on reactive oxygen species (ROS) production by granulocytes in peripheral blood measured by luminol-dependent chemiluminescence registration and its effect on pulmonary lipid peroxidation by malonyldialdehyde (MDA) level measurement. Methods: 62 patients with stable COPD (36 males, mean age 66.8±7.5 years, GOLD stage I-IV) were divided into two treatment groups. Group 1 received bronchodilatators as basal treatment and NAC. Group 2 received NAC plus ICS in addition to basal treatment. Clinical examination, pulmonary function tests and blood collection were performed at baseline (T0) and repeated after 1 (T1), 3 (T3) and 6 months (T6) of treatment. Results: Spontaneous ROS generation had trend to decrease at T3 in both groups, and achieved significant difference at T6 only in group 2 (p=0.0004). At the same time stimulated ROS generation did not significantly change in both groups (p>0.05). Antiperoxide serum activity was increased from T0 to T1 however further levels did not substantially changed. We registered MDA plasma level decrease in both groups during all treatment period, but significant difference from T0 to T6 was observed just in group 2 (1.8 μmol/L vs 1.4 μmol/L, p=0.017). Conclusion: We conclude that combination of oral NAC 1200 mg/day with ICS for 6 months reduces the oxidant burden in airways of stable COPD patients and did not impact in patients treated with NAC alone.