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

Patients with chronic obstructive pulmonary disease (COPD) exhale more hydr ogen 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 muco lytic drug, possesses antioxidant properties as it is a precursor of reduce d glutathione that together with glutathione peroxidase may decompose H2O2 and lipid peroxides. We aimed to determine the effect of NAG, 600 mg effervescent tablets (Fluim ucil), once a day for 12 months, and placebo on the concentration of H2O2 a nd thiobarbituric acid reactive substances (TBARs) in expired breath conden sate and serum levels of two lipid peroxidation products (TBARs, lipid pero xides) 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 th e study. Specimens of expired breath condensate and serum were collected at the randomization visit and then every 3 months over 1 year. The concentra tion of TBARs and H2O2 in expired breath condensate was measured spectroflu orimetrically by the thiobarbituric acid and homovanillic acid methods, res pectively. Serum levels of lipid peroxides were determined spectrophotometr ically after extraction with butanol and pyridine. Initially, H2O2 exhalation did not differ between the placebo and NAC group s up to 6 months of treatment. After this the significant differences were observed. After 9 and 12 months of treatment NBC group exhaled 2.3-fold (0. 17 +/- 0.33 muM vs. 0.41 +/- 0.26 muM, P <0.04) [median=0.01 muM, quartile range (qr)=0.22 vs. median=0.15 muM, qr=0.43] and 26-fold (0.15 +/- 023 muM vs. 0.40 +/-0.25 muM, P <0.05) median=0.00 muM, qr=0.23 vs. median =0.36 m uM, qr = 0.51] less H2O2 than placebo receivers, respectively. No significa nt effect of NAC administration on TBARs exhalation and serum levels of TBA Rs and lipid peroxides were noted over the whole treatment period. Also no significant associations between exhaled H2O2 and concentrations of lipid p eroxidation products were noted in both treatment groups at any time-point. These results indicate that long-term oral administration of NAC attenuates H2O2 formation ill the airways of COPD subjects and prove anti-oxidant act ion of drug. However, further studies are necessary to estimate the clinica l significance of this finding. (C) 2001 HARCOURT PUBLISHERS LTD.