pulmoПульмонологияPULMONOLOGIYA0869-01892541-9617Scientific and Practical Journal “PULMONOLOGIYA” LLCpulmo-209Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL STUDIESПрименение высоких доз N-ацетилцистеина у пациентов со стабильным течением хронической обструктивной болезни легких: двойное слепое рандомизированное плацебо-контролируемое исследование HIACEHigh doses of N-acetylcysteine in patients with stable chronic obstructive pulmonary disease: results of 1-year randomized double-blind placebo-controlled HIACE studyРедакционнаястатья201328062013036272Copyright © Редакционная с., 20132013Редакционная с.Редакционная с.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.pulmonology.ru/pulm/article/view/209

Источник: Tse H.N., Raiteri L., Wong K.Y. et al. High-dose N-acetylcysteine in stable COPD. The 1-year, double-blind, randomized, placebo-controlled HIACE study. CHEST 2013; 144 (1): 106–118.

Источник: Tse H.N., Raiteri L., Wong K.Y. et al. High-dose N-acetylcysteine in stable COPD. The 1-year, double-blind, randomized, placebo-controlled HIACE study. CHEST 2013; 144 (1): 106–118.

стабильная ХОБЛвысокие дозыN-ацетилцистеинантиоксидантымелкие дыхательные путичастота обостренийисследование HIACEstable chronic obstructive pulmonary diseasehigh dosesN-acetylcysteineantioxidantssmall airwaysexacerbation rateHIACE studyReferencesEvans M.D., Pryor W.A. Cigarette smoking, emphysema, and damage to alpha 1-proteinase inhibitor. Am. J. Physiol. 1994; 266 (6, Pt 1): L593–L611.Evans M.D., Pryor W.A. Cigarette smoking, emphysema, and damage to alpha 1-proteinase inhibitor. Am. J. Physiol. 1994; 266 (6, Pt 1): L593–L611.Rahman I., MacNee W. Oxidative stress and regulation of glutathione in lung inflammation . Eur. Respir. J. 2000; 16 (3): 534–554.Rahman I., MacNee W. Oxidative stress and regulation of glutathione in lung inflammation . Eur. Respir. J. 2000; 16 (3): 534–554.Sadowska A.M., Manuel,Y,Keenoy B., De Backer W.A. Antioxidant and anti-infl ammatory efficacy of NAC in the treatment of COPD: discordant in vitro and in vivo doseeffects: a review. Pulm. Pharmacol. Ther. 2007; 20 (1): 9–22.Sadowska A.M., Manuel,Y,Keenoy B., De Backer W.A. Antioxidant and anti-infl ammatory efficacy of NAC in the treatment of COPD: discordant in vitro and in vivo doseeffects: a review. Pulm. Pharmacol. Ther. 2007; 20 (1): 9–22.Aruoma O.I., Halliwell B., Hoey B.M., Butler J. The antioxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid . Free Radic. Biol. Med. 1989; 6 (6): 593–597.Aruoma O.I., Halliwell B., Hoey B.M., Butler J. The antioxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid . Free Radic. Biol. Med. 1989; 6 (6): 593–597.Cotgreave I.A. N-acetylcysteine: pharmacological considerations and experimental and clinical applications. Adv. Pharmacol. 1997; 38: 205–227.Cotgreave I.A. N-acetylcysteine: pharmacological considerations and experimental and clinical applications. Adv. Pharmacol. 1997; 38: 205–227.Moldeus P., Cotgreave I.A., Berggren M. Lung protection by a thiol-containing antioxidant: N-acetylcysteine. Respiration 1986; 50 (Suppl. 1): 31–42.Moldeus P., Cotgreave I.A., Berggren M. Lung protection by a thiol-containing antioxidant: N-acetylcysteine. Respiration 1986; 50 (Suppl. 1): 31–42.Poole P., Black P.N. Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease. Cochrane Database Syst. Rev. 2010; (2): CD001287.Poole P., Black P.N. Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease. Cochrane Database Syst. Rev. 2010; (2): CD001287.Grandjean E.M., Berthet P., Ruffmann R., Leuenberger P. Efficacy of oral long-term N-acetylcysteine in chronic bronchopulmonary disease: a meta-analysis of published double-blind, placebo-controlled clinical trials. Clin. Ther. 2000; 22 (2): 209–221.Grandjean E.M., Berthet P., Ruffmann R., Leuenberger P. Efficacy of oral long-term N-acetylcysteine in chronic bronchopulmonary disease: a meta-analysis of published double-blind, placebo-controlled clinical trials. Clin. Ther. 2000; 22 (2): 209–221.Decramer M., Rutten,van Molken M., Dekhuijzen P.N. et al. Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomised placebocontrolled trial. Lancet 2005; 365 (9470): 1552–1560.Decramer M., Rutten,van Molken M., Dekhuijzen P.N. et al. Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomised placebocontrolled trial. Lancet 2005; 365 (9470): 1552–1560.Antonelli,Incalzi R., Imperiale C., Bellia V. et al. Do GOLD stages of COPD severity really correspond to differences in health status? Eur. Respir. J. 2003; 22 (3): 444–449.Antonelli,Incalzi R., Imperiale C., Bellia V. et al. Do GOLD stages of COPD severity really correspond to differences in health status? Eur. Respir. J. 2003; 22 (3): 444–449.McFadden E.R. Jr., Linden D.A. A reduction in maximum midexpiratory flow rate. A spirographic manifestation of small airway disease. Am. J. Med. 1972; 52 (6): 725–737.McFadden E.R. Jr., Linden D.A. A reduction in maximum midexpiratory flow rate. A spirographic manifestation of small airway disease. Am. J. Med. 1972; 52 (6): 725–737.Gelb A.F., Zamel N. Simplified diagnosis of small-airway obstruction. N. Engl. J. Med. 1973; 288 (8): 395–398.Gelb A.F., Zamel N. Simplified diagnosis of small-airway obstruction. N. Engl. J. Med. 1973; 288 (8): 395–398.Goldman M.D., Saadeh C., Ross D. Clinical applications of forced oscillation to assess peripheral airway function. Respir. Physiol. Neurobiol. 2005; 148 (1–2): 179–194.Goldman M.D., Saadeh C., Ross D. Clinical applications of forced oscillation to assess peripheral airway function. Respir. Physiol. Neurobiol. 2005; 148 (1–2): 179–194.Grimby G., Takishima T., Graham W. et al. Frequency dependence of flow resistance in patients with obstructive lung disease. J. Clin. Invest. 1968; 47 (6): 1455–1465.Grimby G., Takishima T., Graham W. et al. Frequency dependence of flow resistance in patients with obstructive lung disease. J. Clin. Invest. 1968; 47 (6): 1455–1465.Evans T.M., Rundell K.W., Beck K.C. et al. Airway narrowing measured by spirometry and impulse oscillometry following room temperature and cold temperature exercise. Chest 2005; 128 (4): 2412–2419.Evans T.M., Rundell K.W., Beck K.C. et al. Airway narrowing measured by spirometry and impulse oscillometry following room temperature and cold temperature exercise. Chest 2005; 128 (4): 2412–2419.US National Institutes of Health. The effect of high dose N-acetylcysteine on airtrapping and airway resistance of chronic obstructive pulmonary disease – a double-blinded, randomized, placebo-controlled trial. NCT01136239. Clinical Trials.gov. Bethesda, MD: National Institutes of Health; 2010. http://www.clinicaltrials.gov/ct2/show/mNCT01136239. Updated June 2, 2010.US National Institutes of Health. The effect of high dose N-acetylcysteine on airtrapping and airway resistance of chronic obstructive pulmonary disease – a double-blinded, randomized, placebo-controlled trial. NCT01136239. Clinical Trials.gov. Bethesda, MD: National Institutes of Health; 2010. http://www.clinicaltrials.gov/ct2/show/mNCT01136239. Updated June 2, 2010.Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Global Initiative for Chronic Obstructive Lung Disease website. http://www.gold,copd.org/uploads/users/fi les/GOLD-Report-2011-Feb21.pdf. Accessed December 7, 2012.Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Global Initiative for Chronic Obstructive Lung Disease website. http://www.gold,copd.org/uploads/users/fi les/GOLD-Report-2011-Feb21.pdf. Accessed December 7, 2012.American Thoracic Society. Standardization of spirometry, 1994 update. Am. J. Respir. Crit. Care Med. 1995; 152 (3): 1107–1136.American Thoracic Society. Standardization of spirometry, 1994 update. Am. J. Respir. Crit. Care Med. 1995; 152 (3): 1107–1136.Ip M.S., Ko F.W., Lau A.C. et al.; Hong Kong Thoracic Society; American College of Chest Physicians (Hong Kong and Macau Chapter). Updated spirometric reference values for adult Chinese in Hong Kong and implications on clinical utilization. Chest 2006; 129 (2): 384–392.Ip M.S., Ko F.W., Lau A.C. et al.; Hong Kong Thoracic Society; American College of Chest Physicians (Hong Kong and Macau Chapter). Updated spirometric reference values for adult Chinese in Hong Kong and implications on clinical utilization. Chest 2006; 129 (2): 384–392.Oostveen E., MacLeod D., Lorino H. et al. ERS Task Force on Respiratory Impedance Measurements. The forced oscillation technique in clinical practice: methodology, recommendations and future developments. Eur. Respir. J. 2003; 22 (6):1026–1041.Oostveen E., MacLeod D., Lorino H. et al. ERS Task Force on Respiratory Impedance Measurements. The forced oscillation technique in clinical practice: methodology, recommendations and future developments. Eur. Respir. J. 2003; 22 (6):1026–1041.Crim C., Celli B., Edwards L.D. et al. ECLIPSE investigators. Respiratory system impedance with impulse oscillometry in healthy and COPD subjects: ECLIPSE baseline results. Respir. Med. 2011; 105 (7): 1069–1078.Crim C., Celli B., Edwards L.D. et al. ECLIPSE investigators. Respiratory system impedance with impulse oscillometry in healthy and COPD subjects: ECLIPSE baseline results. Respir. Med. 2011; 105 (7): 1069–1078.Macklem P.T., Mead J. Resistance of central and peripheral airways measured by a retrograde catheter. J. Appl. Physiol. 1967; 22 (3): 395–401.Macklem P.T., Mead J. Resistance of central and peripheral airways measured by a retrograde catheter. J. Appl. Physiol. 1967; 22 (3): 395–401.Burgel P.R., Bourdin A., Chanez P. et al. Update on the roles of distal airways in COPD. Eur. Respir. Rev. 2011; 20 (119): 7–22.Burgel P.R., Bourdin A., Chanez P. et al. Update on the roles of distal airways in COPD. Eur. Respir. Rev. 2011; 20 (119): 7–22.Hogg J.C., Chu F., Utokaparch S. et al. The nature of smallairway obstruction in chronic obstructive pulmonary disease. N. Engl. J. Med. 2004; 350 (26): 2645–2653.Hogg J.C., Chu F., Utokaparch S. et al. The nature of smallairway obstruction in chronic obstructive pulmonary disease. N. Engl. J. Med. 2004; 350 (26): 2645–2653.Caramori G., Di Gregorio C., Carlstedt I. et al. Mucin expression in peripheral airways of patients with chronic obstructive pulmonary disease. Histopathology 2004; 45 (5): 477–484.Caramori G., Di Gregorio C., Carlstedt I. et al. Mucin expression in peripheral airways of patients with chronic obstructive pulmonary disease. Histopathology 2004; 45 (5): 477–484.Rabe K.F., Hurd S., Anzueto A. et al. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the Downloaded From: http://journal.publications.chestnet.org/by a Zambon Group User on 07/02/2013.Rabe K.F., Hurd S., Anzueto A. et al. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the Downloaded From: http://journal.publications.chestnet.org/by a Zambon Group User on 07/02/2013.Bourdin A., Burgel P.R., Chanez P. et al. Recent advances in COPD: pathophysiology, respiratory physiology and clinical aspects, including comorbidities. Eur. Respir. Rev. 2009; 18 (114): 198–212.Bourdin A., Burgel P.R., Chanez P. et al. Recent advances in COPD: pathophysiology, respiratory physiology and clinical aspects, including comorbidities. Eur. Respir. Rev. 2009; 18 (114): 198–212.Calverley P.M., Koulouris N.G. Flow limitation and dynamic hyperinflation: key concepts in modern respiratory physiology. Eur. Respir. J. 2005; 25 (1): 186–199.Calverley P.M., Koulouris N.G. Flow limitation and dynamic hyperinflation: key concepts in modern respiratory physiology. Eur. Respir. J. 2005; 25 (1): 186–199.King G.G., Downie S.R., Verbanck S. et al. Effects of methacholine on small airway function measured by forced oscilation technique and multiple breath nitrogen washout in normal subjects. Respir. Physiol. Neurobiol. 2005; 148 (1–2): 165–177.King G.G., Downie S.R., Verbanck S. et al. Effects of methacholine on small airway function measured by forced oscilation technique and multiple breath nitrogen washout in normal subjects. Respir. Physiol. Neurobiol. 2005; 148 (1–2): 165–177.Mahut B., Caumont,Prim A., Plantier L. et al. Relationships between respiratory and airway resistances and activityrelated dyspnea in patients with chronic obstructive pulmonary disease. Int. J. Chron. Obstruct. Pulmon. Dis. 2012; 7: 165–171.Mahut B., Caumont,Prim A., Plantier L. et al. Relationships between respiratory and airway resistances and activityrelated dyspnea in patients with chronic obstructive pulmonary disease. Int. J. Chron. Obstruct. Pulmon. Dis. 2012; 7: 165–171.Brochard L., Pelle G., de Palmas J. et al. Density and frequency dependence of resistance in early airway obstruction. Am. Rev. Respir. Dis. 1987; 135 (3): 579–584.Brochard L., Pelle G., de Palmas J. et al. Density and frequency dependence of resistance in early airway obstruction. Am. Rev. Respir. Dis. 1987; 135 (3): 579–584.Faria A.C., Costa A.A., Lopes A.J. et al. Forced oscillation technique in the detection of smoking-induced respiratory alterations: diagnostic accuracy and comparison with spirometry. Clinics (Sao Paulo) 2010; 65 (12): 1295–1304.Faria A.C., Costa A.A., Lopes A.J. et al. Forced oscillation technique in the detection of smoking-induced respiratory alterations: diagnostic accuracy and comparison with spirometry. Clinics (Sao Paulo) 2010; 65 (12): 1295–1304.Black P.N., Morgan,Day A., McMillan T.E. et al. Randomised, controlled trial of N-acetylcysteine for treatment of acute exacerbations of chronic obstructive pulmonary disease (ISRCTN21676344) (ISRCTN21676344). BMC Pulm. Med. 2004; 4: 13.Black P.N., Morgan,Day A., McMillan T.E. et al. Randomised, controlled trial of N-acetylcysteine for treatment of acute exacerbations of chronic obstructive pulmonary disease (ISRCTN21676344) (ISRCTN21676344). BMC Pulm. Med. 2004; 4: 13.Poole P.J., Black P.N. Oral mucolytic drugs for exacerbations of chronic obstructive pulmonary disease: systematic review. Br. Med. J. 2001; 322 (7297): 1271–1274.Poole P.J., Black P.N. Oral mucolytic drugs for exacerbations of chronic obstructive pulmonary disease: systematic review. Br. Med. J. 2001; 322 (7297): 1271–1274.Benrahmoune M., Therond P., Abedinzadeh Z. The reaction of superoxide radical with N-acetylcysteine. Free Radic. Biol. Med. 2000; 29 (8): 775–782.Benrahmoune M., Therond P., Abedinzadeh Z. The reaction of superoxide radical with N-acetylcysteine. Free Radic. Biol. Med. 2000; 29 (8): 775–782.Gressier B., Cabanis A., Lebegue S. et al. Decrease of hypochlorous acid and hydroxyl radical generated by stimulated human neutrophils: comparison in vitro of some thiol-containing drugs. Meth. Find Exp. Clin. Pharmacol. 1994; 16 (1): 9–13.Gressier B., Cabanis A., Lebegue S. et al. Decrease of hypochlorous acid and hydroxyl radical generated by stimulated human neutrophils: comparison in vitro of some thiol-containing drugs. Meth. Find Exp. Clin. Pharmacol. 1994; 16 (1): 9–13.Kharazmi A., Nielsen H., Schiotz P.O. N-acetylcysteine inhibits human neutrophil and monocyte chemotaxis and oxidative metabolism. Int. J. Immunopharmacol. 1988; 10 (1): 39–46.Kharazmi A., Nielsen H., Schiotz P.O. N-acetylcysteine inhibits human neutrophil and monocyte chemotaxis and oxidative metabolism. Int. J. Immunopharmacol. 1988; 10 (1): 39–46.Stolarek R., Bialasiewicz P., Nowak D. N-acetylcysteine effect on the luminol-dependent chemiluminescence pattern of reactive oxygen species generation by human polymor phonuclear leukocytes . Pulm. Pharmacol. Ther. 2002; 15 (4): 385–392.Stolarek R., Bialasiewicz P., Nowak D. N-acetylcysteine effect on the luminol-dependent chemiluminescence pattern of reactive oxygen species generation by human polymor phonuclear leukocytes . Pulm. Pharmacol. Ther. 2002; 15 (4): 385–392.Borgstrom L., Kagedal B. Dose dependent pharmacokinetics of N-acetylcysteine after oral dosing to man. Biopharm Drug Dispos. 1990; 11 (2): 131–136.Borgstrom L., Kagedal B. Dose dependent pharmacokinetics of N-acetylcysteine after oral dosing to man. Biopharm Drug Dispos. 1990; 11 (2): 131–136.Bridgeman M.M., Marsden M., Selby C. et al. Effect of N-acetyl cysteine on the concentrations of thiols in plasma, bronchoalveolar lavage fluid, and lung tissue. Thorax 1994; 49 (7): 670–675.Bridgeman M.M., Marsden M., Selby C. et al. Effect of N-acetyl cysteine on the concentrations of thiols in plasma, bronchoalveolar lavage fluid, and lung tissue. Thorax 1994; 49 (7): 670–675.De Benedetto F., Aceto A., Dragani B. et al. Long-term oral n-acetylcysteine reduces exhaled hydrogen peroxide in stable COPD. Pulm. Pharmacol. Ther. 2005; 18 (1): 41–47.De Benedetto F., Aceto A., Dragani B. et al. Long-term oral n-acetylcysteine reduces exhaled hydrogen peroxide in stable COPD. Pulm. Pharmacol. Ther. 2005; 18 (1): 41–47.Kasielski M., Nowak D. Long-term administration of N-acetylcysteine decreases hydrogen peroxide exhalation in subjects with chronic obstructive pulmonary disease. Respir. Med. 2001; 95 (6): 448–456.Kasielski M., Nowak D. Long-term administration of N-acetylcysteine decreases hydrogen peroxide exhalation in subjects with chronic obstructive pulmonary disease. Respir. Med. 2001; 95 (6): 448–456.Demedts M., Behr J., Buhl R. et al. IFIGENIA Study Group. High-dose acetylcysteine in idiopathic pulmonary fibrosis. N. Engl. J. Med. 2005; 353 (21): 2229–2242.Demedts M., Behr J., Buhl R. et al. IFIGENIA Study Group. High-dose acetylcysteine in idiopathic pulmonary fibrosis. N. Engl. J. Med. 2005; 353 (21): 2229–2242.Cotgreave I.A., Moldeus P. Lung protection by thiol-containing antioxidants. Bull. Eur. Physiopathol. Respir. 1987; 23 (4): 275–277.Cotgreave I.A., Moldeus P. Lung protection by thiol-containing antioxidants. Bull. Eur. Physiopathol. Respir. 1987; 23 (4): 275–277.Jeffery P.K., Rogers D.F., Ayers M.M. Effect of oral acetylcysteine on tobacco smoke-induced secretory cell hyperplasia. Eur. J. Respir. Dis. Suppl. 1985; 139: 117–122.Jeffery P.K., Rogers D.F., Ayers M.M. Effect of oral acetylcysteine on tobacco smoke-induced secretory cell hyperplasia. Eur. J. Respir. Dis. Suppl. 1985; 139: 117–122.Rubio M.L., Sanchez,Cifuentes M.V., Ortega M. et al. N-acetylcysteine prevents cigarette smoke induced small airways alterations in rats. Eur. Respir. J. 2000; 15 (3): 505–511.Rubio M.L., Sanchez,Cifuentes M.V., Ortega M. et al. N-acetylcysteine prevents cigarette smoke induced small airways alterations in rats. Eur. Respir. J. 2000; 15 (3): 505–511.Bridgeman M.M., Marsden M., MacNee W. et al. Cysteine and glutathione concentrations in plasma and bronchoalveolar lavage fluid after treatment with N-acetylcysteine. Thorax 1991; 46 (1): 39–42.Bridgeman M.M., Marsden M., MacNee W. et al. Cysteine and glutathione concentrations in plasma and bronchoalveolar lavage fluid after treatment with N-acetylcysteine. Thorax 1991; 46 (1): 39–42.Stav D., Raz M. Effect of N-acetylcysteine on air trapping in COPD: a randomized placebo-controlled study. Chest 2009; 136 (2): 381–386.Stav D., Raz M. Effect of N-acetylcysteine on air trapping in COPD: a randomized placebo-controlled study. Chest 2009; 136 (2): 381–386.Hanaoka M., Droma Y., Chen Y. et al. Carbocisteine protects against emphysema induced by cigarette smoke extract in rats. Chest 2011; 139 (5): 1101–1108.Hanaoka M., Droma Y., Chen Y. et al. Carbocisteine protects against emphysema induced by cigarette smoke extract in rats. Chest 2011; 139 (5): 1101–1108.Rubio M.L., Martin,Mosquero M.C., Ortega M. et al. Oral N-acetylcysteine attenuates elastase-induced pulmonary emphysema in rats. Chest 2004; 125 (4): 1500–1506.Rubio M.L., Martin,Mosquero M.C., Ortega M. et al. Oral N-acetylcysteine attenuates elastase-induced pulmonary emphysema in rats. Chest 2004; 125 (4): 1500–1506.Zheng J.P., Kang J., Huang S.G. et al. Effect of carbocisteine on acute exacerbation of chronic obstructive pulmonary disease (PEACE Study): a randomised placebo-controlled study. Lancet 2008; 371 (9629): 2013–2018.Zheng J.P., Kang J., Huang S.G. et al. Effect of carbocisteine on acute exacerbation of chronic obstructive pulmonary disease (PEACE Study): a randomised placebo-controlled study. Lancet 2008; 371 (9629): 2013–2018.Niederman M.S., Rafferty T.D., Sasaki C.T. et al. Comparison of bacterial adherence to ciliated and squamous epithelial cells obtained from the human respiratory trac. Am. Rev. Respir. Dis. 1983; 127 (1): 85–90.Niederman M.S., Rafferty T.D., Sasaki C.T. et al. Comparison of bacterial adherence to ciliated and squamous epithelial cells obtained from the human respiratory trac. Am. Rev. Respir. Dis. 1983; 127 (1): 85–90.Suer E., Sayrac S., Sarinay E. et al. Variation in the attachment of Streptococcus pneumoniae to human pharyngeal epithelial cells after treatment with S-carboxymethylcysteine. J. Infect. Chemother. 2008; 14 (4): 333–336.Suer E., Sayrac S., Sarinay E. et al. Variation in the attachment of Streptococcus pneumoniae to human pharyngeal epithelial cells after treatment with S-carboxymethylcysteine. J. Infect. Chemother. 2008; 14 (4): 333–336.Gerrits C.M., Herings R.M., Leufkens H.G., Lammers J.W. N-acetylcysteine reduces the risk of re-hospitalisation among patients with chronic obstructive pulmonary disease. Eur. Respir. J. 2003; 21 (5): 795–798.Gerrits C.M., Herings R.M., Leufkens H.G., Lammers J.W. N-acetylcysteine reduces the risk of re-hospitalisation among patients with chronic obstructive pulmonary disease. Eur. Respir. J. 2003; 21 (5): 795–798.

The authors declare that there are no conflicts of interest present.