High-dose N-acetylcysteine in stable COPD: The 1-year, double-blind, randomized, placebo-controlled HIACE study

Chest

Volumn 144, Issue 1, 2013, Pages 106-118

  Tse, Hoi Nam ^a   Raiteri, Luca ^c   Wong, King Ying ^b   Yee, Kwok Sang ^b   Ng, Lai Yun ^a   Wai, Ka Yan ^a   Loo, Ching Kong ^a   Chan, Ming Houng ^a  

^a KWONG WAH HOSPITAL   (Hong Kong)

^b Wong Tai Sin Hospital   (Hong Kong)

^c Zambon Company SpA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLCYSTEINE; BETA 2 ADRENERGIC RECEPTOR STIMULATING AGENT; CORTICOSTEROID; MUSCARINIC AGENT; PLACEBO;

ADULT; AGED; ARTICLE; CHINESE; CHRONIC OBSTRUCTIVE LUNG DISEASE; CONTROLLED STUDY; DIARRHEA; DISEASE EXACERBATION; DOUBLE BLIND PROCEDURE; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; EXERCISE; FEMALE; FORCED EXPIRATORY FLOW; FORCED EXPIRATORY VOLUME; FORCED VITAL CAPACITY; GASTROESOPHAGEAL REFLUX; GASTROINTESTINAL SYMPTOM; HONG KONG; HOSPITAL ADMISSION; HUMAN; INSPIRATORY CAPACITY; LUNG FUNCTION TEST; MAJOR CLINICAL STUDY; MALE; MODIFIED MEDICAL RESEARCH COUNCIL DYSPNEA SCALE; NAMED INVENTORIES, QUESTIONNAIRES AND RATING SCALES; OSCILLATION; PRIORITY JOURNAL; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL; ST. GEORGE RESPIRATORY QUESTIONNAIRE; TREATMENT OUTCOME; WALKING;

EID: 84880047842     PISSN: 00123692     EISSN: 19313543     Source Type: Journal    
DOI: 10.1378/chest.12-2357     Document Type: Article

References (54)

1. Evans MD, Pryor WA. Cigarette smoking, emphysema, and damage to alpha 1-proteinase inhibitor. Am J Physiol. 1994; 266 (6 pt 1): L593-L611.
2. Rahman I, MacNee W. Oxidative stress and regulation of glutathione in lung inflammation. Eur Respir J. 2000; 16( 3): 534-554.
3. Sadowska AM, Manuel-Y-Keenoy B, De Backer WA. Antioxidant and anti-inflammatory efficacy of NAC in the treatment of COPD: discordant in vitro and in vivo dose-effects: a review. Pulm Pharmacol Ther. 2007; 20 (1): 9-22.
4. Aruoma OI, Halliwell B, Hoey BM, 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.
5. Cotgreave IA. N-acetylcysteine: pharmacological considerations and experimental and clinical applications. Adv Pharmacol. 1997; 38: 205-227.
6. Moldéus P, Cotgreave IA, Berggren M. Lung protection by a thiol-containing antioxidant: N-acetylcysteine. Respiration. 1986; 50 (Suppl 1): 31-42.
7. Poole P, Black PN. Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2010; (2): CD001287.
8. Grandjean EM, 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.
9. Decramer M, Rutten-van Mölken M, Dekhuijzen PN, et al. Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomised placebo-controlled trial. Lancet. 2005; 365 (9470): 1552-1560.
10. Antonelli-Incalzi R, Imperiale C, Bellia V, et al; SaRA Investigators. Do GOLD stages of COPD severity really correspond to differences in health status? Eur Respir J. 2003; 22 (3): 444-449.
11. McFadden ER Jr, Linden DA. A reduction in maximum midexpiratory flow rate. A spirographic manifestation of small airway disease. Am J Med. 1972; 52 (6): 725-737.
12. Gelb AF, Zamel N. Simplified diagnosis of small-airway obstruction. N Engl J Med. 1973; 288 (8): 395-398.
13. Goldman MD, Saadeh C, Ross D. Clinical applications of forced oscillation to assess peripheral airway function. Respir Physiol Neurobiol. 2005; 148 (1-2): 179-194.
14. Grimby G, Takishima T, Graham W, Macklem P, Mead J. Frequency dependence of flow resistance in patients with obstructive lung disease. J Clin Invest. 1968; 47( 6): 1455-1465.
15. Evans TM, Rundell KW, Beck KC, Levine AM, Baumann JM. Airway narrowing measured by spirometry and impulse oscillometry following room temperature and cold temperature exercise. Chest. 2005; 128 (4): 2412-2419.
16. 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. ClinicalTrials. gov. Bethesda, MD: National Institutes of Health; 2010. http://www.clinicaltrials.gov/ct2/show/NCT01136239. Updated June 2, 2010.
17. 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.goldcopd.org/uploads/users/files/GOLD-Report-2011-Feb21. pdf. Accessed December 7, 2012.
18. American Thoracic Society. Standardization of spirometry, 1994 update. Am J Respir Crit Care Med. 1995; 152 (3): 1107-1136.
19. Ip MS, Ko FW, Lau AC, 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.
20. 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.
21. Crim C, Celli B, Edwards LD, 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.
22. Macklem PT, Mead J. Resistance of central and peripheral airways measured by a retrograde catheter. J Appl Physiol. 1967; 22 (3): 395-401.
23. Burgel PR, Bourdin A, Chanez P, et al. Update on the roles of distal airways in COPD. Eur Respir Rev. 2011; 20 (119): 7-22.
24. Hogg JC, 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.
25. 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.
26. Rabe KF, Hurd S, Anzueto A, et al; Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2007; 176 (6): 532-555.
27. Bourdin A, Burgel PR, Chanez P, Garcia G, Perez T, Roche N. Recent advances in COPD: pathophysiology, respiratory physiology and clinical aspects, including comorbidities. Eur Respir Rev. 2009; 18 (114): 198-212.
28. Calverley PM, Koulouris NG. Flow limitation and dynamic hyperinflation: key concepts in modern respiratory physiology. Eur Respir J. 2005; 25 (1): 186-199.
29. King GG, Downie SR, Verbanck S, et al. Effects of methacholine on small airway function measured by forced oscillation technique and multiple breath nitrogen washout in normal subjects. Respir Physiol Neurobiol. 2005; 148 (1-2): 165-177.
30. Mahut B, Caumont-Prim A, Plantier L, et al. Relationships between respiratory and airway resistances and activity-related dyspnea in patients with chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2012; 7: 165-171.
31. 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.
32. Faria AC, Costa AA, Lopes AJ, Jansen JM, Melo PL. 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.
33. Black PN, Morgan-Day A, McMillan TE, Poole PJ, Young RP. Randomised, controlled trial of N-acetylcysteine for treatment of acute exacerbations of chronic obstructive pulmonary disease [ISRCTN21676344] [ISRCTN21676344]. BMC Pulm Med. 2004; 4: 13.
34. Poole PJ, Black PN. Oral mucolytic drugs for exacerbations of chronic obstructive pulmonary disease: systematic review. BMJ. 2001; 322 (7297): 1271-1274.
35. Benrahmoune M, Thérond P, Abedinzadeh Z. The reaction of superoxide radical with N-acetylcysteine. Free Radic Biol Med. 2000; 29 (8): 775-782.
36. 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. Methods Find Exp Clin Pharmacol. 1994; 16 (1): 9-13.
37. Kharazmi A, Nielsen H, Schiøtz PO. N-acetylcysteine inhibits human neutrophil and monocyte chemotaxis and oxidative metabolism. Int J Immunopharmacol. 1988; 10 (1): 39-46.
38. Stolarek R, Białasiewicz 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.
39. Borgström L, Kågedal B. Dose dependent pharmacokinetics of N-acetylcysteine after oral dosing to man. Biopharm Drug Dispos. 1990; 11 (2): 131-136.
40. Bridgeman MM, Marsden M, Selby C, Morrison D, MacNee W. Effect of N-acetyl cysteine on the concentrations of thiols in plasma, bronchoalveolar lavage fluid, and lung tissue. Thorax. 1994; 49 (7): 670-675.
41. 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.
42. 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.
43. 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.
44. Cotgreave IA, Moldéus P. Lung protection by thiol-containing antioxidants. Bull Eur Physiopathol Respir. 1987; 23( 4): 275-277.
45. Jeffery PK, Rogers DF, Ayers MM. Effect of oral acetylcysteine on tobacco smoke-induced secretory cell hyperplasia. Eur J Respir Dis Suppl. 1985; 139: 117-122.
46. Rubio ML, Sanchez-Cifuentes MV, Ortega M, et al. N-acetylcysteine prevents cigarette smoke induced small airways alterations in rats. Eur Respir J. 2000; 15 (3): 505-511.
47. Bridgeman MM, Marsden M, MacNee W, Flenley DC, Ryle AP. Cysteine and glutathione concentrations in plasma and bronchoalveolar lavage fluid after treatment with N-acetylcysteine. Thorax. 1991; 46 (1): 39-42.
48. Stav D, Raz M. Effect of N-acetylcysteine on air trapping in COPD: a randomized placebo-controlled study. Chest. 2009; 136 (2): 381-386.
49. 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.
50. Rubio ML, Martin-Mosquero MC, Ortega M, Peces-Barba G, González-Mangado N. Oral N-acetylcysteine attenuates elastaseinduced pulmonary emphysema in rats. Chest. 2004; 125 (4): 1500-1506.
51. Zheng JP, Kang J, Huang SG, 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.
52. Niederman MS, Rafferty TD, Sasaki CT, Merrill WW, Matthay RA, Reynolds HY. Comparison of bacterial adherence to ciliated and squamous epithelial cells obtained from the human respiratory tract. Am Rev Respir Dis. 1983; 127( 1): 85-90.
53. 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.
54. Gerrits CM, Herings RM, Leufkens HG, Lammers JW. N-acetylcysteine reduces the risk of re-hospitalisation among patients with chronic obstructive pulmonary disease. Eur Respir J. 2003; 21 (5): 795-798.