Long-term administration of N-acetylcysteine decreases hydrogen peroxide exhalation in subjects with chronic obstructive pulmonary disease

Abstract

Patients with chronic obstructive pulmonary disease (COPD) exhale more hydrogen peroxide (H2O2) and lipid peroxidation products than healthy subjects. This may reflect oxidative stress in the airways that plays important role in the development and progression of COPD. N-acetylcysteine (NAC), a mucolytic drug, possesses antioxidant properties as it is a precursor of reduced glutathione that together with glutathione peroxidase may decompose H2O2 and lipid peroxides. We aimed to determine the effect of NAC, 600 mg effervescent tablets (Fluimucil), once a day for 12 months, and placebo on the concentration of H2O2 and thiobarbituric acid reactive substances (TBARs) in expired breath condensate and serum levels of two lipid peroxidation products (TBARs, lipid peroxides) in patients with COPD. The study was performed as a double-blind, double-dummy comparison between active drug and placebo in two parallel groups. Forty-four outpatients with stable COPD (22 in the NAC group and 22 in the placebo group) completed the study. Specimens of expired breath condensate and serum were collected at the randomization visit and then every 3 months over 1 year. The concentration of TBARs and H2O2 in expired breath condensate was measured spectrofluorimetrically by the thiobarbituric acid and homovanillic acid methods, respectively. Serum levels of lipid peroxides were determined spectrophotometrically after extraction with butanol and pyridine. Initially, H2O2 exhalation did not differ between the placebo and NAC groups up to 6 months of treatment. After this the significant differences were observed. After 9 and 12 months of treatment NAC group exhaled 2.3-fold (0.17 ± 0.33 μM vs. 0.41 ± 0.26 μM, P<0.04) [median =0.01 μM, quartile range (qr) = 0.22 vs. median =0.15 μM, qr=0.43] and 2.6-fold (0.15±0.23 μM vs. 0.40 ± 0.25 μM, P<0.05) median=0.00 μM, qr=0.23 vs. median = 0.36 μM, qr = 0.51] less H2O2 than placebo receivers, respectively. No significant effect of NAC administration on TBARs exhalation and serum levels of TBARs and lipid peroxides were noted over the whole treatment period. Also no significant associations between exhaled H2O2 and concentrations of lipid peroxidation products were noted in both treatment groups at any time-point. These results indicate that long-term oral administration of NAC attenuates H2O2 formation in the airways of COPD subjects and prove anti-oxidant action of drug. However, further studies are necessary to estimate the clinical significance of this finding. © 2001 Harcourt Publishers Ltd.