Objective: This study was performed to confirm the efficacy of a 6-month therapy with a formulation of N-acetylcysteine (NAC; 600 mg/day p.o.) on frequency and severity of exacerbations in patients suffering from chronic obstructive pulmonary disease (COPD). Methods: One hundred sixty-nine patients attending five Italian centres were recruited in an open, randomized, controlled study. The patients were randomly allocated to standard therapy plus NAC 600 mg once a day or standard therapy alone over a 6-month period. At baseline, medical history was evaluated, and physical examination was performed; occurrence and severity of exacerbations and side effects of NAC were analyzed after 3 and 6 months. Results: The results showed a decreased number of exacerbations (by 41%) in the group of patients treated with NAC and standard treatment: 46 patients had at least one exacerbation as compared with 63 patients of the group treated with standard therapy alone. Also the number of the patients with two or more exacerbations was lower in the NAC group (26%) than in the standard-therapy group (49%). The number of sick days was less (82) in the NAC group as compared with the standard-therapy group (155). There was a small but significant improvement in FEV1 and MEF50 in the NAC group. NAC once a day was well tolerated. There were no differences in the number of side effects reported in both groups. Conclusions: These data confirm results of previous studies which reported a reduction in the number of exacerbations in patients having moderate to severe COPD treated with the antioxidant NAC. Further, the once-daily formulation is well tolerated and is likely to improve patient compliance with the prescribed regimen.

Keywords:
Chronic obstructive pulmonary disease, Exacerbations, N-actylcysteine, Drug dosage
1.
American Thoracic Society: Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1995;152(suppl):77–120.
2.
Siafakas NM, Vermeire P, Pride NB, et al: Optimal assessment and management of chronic obstructive pulmonary disease. Eur Respir J 1995;8:1398–1420.
3.
Maier KL, Leuschel L, Constabel U: Increased oxidised methionine residues in BAL fluid proteins in acute or chronic bronchitis. Eur Respir J 1992;5:651–658.
4.
Dekhuijzen PNR, Aben KKH, Dekker I, et al: Increased exhalation of hydrogen peroxide in patients with stable and unstable COPD. Am J Respir Crit Care Med 1996;154:813–816.
5.
Grassi C, Morandini GC: A controlled trial of intermittent oral acetylcysteine in the long-term treatment of chronic bronchitis. Eur J Clin Pharmacol 1976;9:393–396.
6.
Multicenter Study Group: Long-term oral acetylcysteine in chronic bronchitis: A double-blind controlled study. Eur J Clin Respir Dis 1980;61(suppl 111):93:108.
7.
Boman G, Backer U, Larsson S, Melander B, Wahlander L: Oral acetylcysteine reduces exacerbation rate in chronic bronchitis: Report of a trial organised by the Swedish Society for Pulmonary Diseases. Eur J Respir Dis 1983;64:405–415.
8.
Jackson M, Barnes J, Cooksey P: Efficacy and tolerability of oral acetylcysteine (Fabrol) in chronic bronchitis: A double-blind placebo-controlled study: J Med Res 1984;198–205.
9.
British Thoracic Society Research Committee: Oral N-acetylcysteine and exacerbation rates with chronic bronchitis and severe airway obstruction. Thorax 1985;40:832–835.
10.
Meister R: Langzeittherapie mit Acetylcystein Retard-Tabletten bei Patienten mit chronischer Bronchitis: Eine doppelblinde placebokontrollierte Studie. Forum Prakt Allg Arzt 1986;25:18–22.
11.
Parr GD, Huitson A: Oral Fabrol (oral N-acetylcysteine) in chronic bronchitis. Br J Dis Chest 1987;81:341–348.
12.
Rasmussen JB, Glennon C: Reduction in days of illness after long-term treatment with N-acetylcysteine controlled-release tablets in patients with chronic bronchitis. Eur Respir J 1988;1:351–355.
13.
Hansen NCG, Skriver A, Bronsen-Riis L, et al: Orally administered N-acetylcysteine may improve general well-being in patients with mild chronic bronchitis. Respir Med 1994;88:531–535.
14.
Lundbäck B, Lindström M, Andersson S, Nyström L, Rosenhall L, Stjerberg N: Possible effect of acetylcysteine on lung function. Eur Respir J 1992;5(suppl 15):289.
15.
Quanjer PH: Standardised lung function testing: Report Working Party standardisation of Lung Function tests’ of the European Respiratory Society and the European Community for Coal and Steel. Eur Respir J 1993;6(suppl 16):1–100.
16.
Moldeus P, Cotgreave IA, Berggren M: Lung protection by a thiol-containing antioxidant: N-acetylcysteine. Respiration 1986;50:31–42.
17.
Rogers DF, Jeffery PK: Inhibiton by oral N-acetylcysteine of cigarette smoke-induced ‘bronchitis’ in the rat. Exp Lung Res 1986;10:267–283.
18.
Bridges RB: Protective action of thiols on neutrophil function. Eur J Respir Dis 1985;66(suppl 139):40–48.
19.
Voisin C, Aerts C, Fournier E, Firlik M: Acute effects of tobacco smoke on alveolar macrophages cultured in gas phase. Eur J Respir Dis 1985;66(suppl 139):76–81.
20.
Borregaard N, Jensen HS, Bjerrum OW: Prevention of tissue damage: Inhibition of myeloperoxidase mediated inactivation of alpha 1-proteinase inhibitor by N-acetylcysteine, glutathione, and methionine. Agents Actions 1987;22:255–260.
21.
Riise GC, Larsson S, Larsson P, Jeansson S, Andersson BA: The intrabronchial microbial flora in chronic bronchitis patients: A target for N-acetylcysteine therapy? Eur Respir J 1994;7:94–101.
22.
De Flora S, Grassi C, Carati L: Attenuation of influenza symptomatology and improvement of immunological parameters due to long-term treatment with N-acetylcysteine. Eur Respir J 1997;10:1535–1541.
23.
Murphy TF, Sethi S: Bacterial infection in chronic obstructive pulmonary disease. Am Rev Respir Dis 1992;146:1067–1083.
© 1999 S. Karger AG, Basel
1999
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.