Carbocysteine in the Management of Stable COPD: Are Its Antioxidant and Anti-Inflammatory Properties Clinically Relevant?

Authors

  • Jordan Minov Institute for Occupational Health of Republic of Macedonia, Skopje – WHO Collaborating Center, Skopje
  • Jovanka Karadzinska-Bislimovska Institute for Occupational Health of Republic of Macedonia, Skopje – WHO Collaborating Center, Skopje
  • Tatjana Petrova Department of Pharmacy Practice, Chicago State University, Chicago
  • Kristin Vasilevska Institute for Epidemiology and Biostatistics, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje
  • Saso Stoleski Institute for Occupational Health of Republic of Macedonia, Skopje – WHO Collaborating Center, Skopje
  • Dragan Mijakoski Institute for Occupational Health of Republic of Macedonia, Skopje – WHO Collaborating Center, Skopje
  • Aneta Atanasovska Institute for Occupational Health of Republic of Macedonia, Skopje – WHO Collaborating Center, Skopje

DOI:

https://doi.org/10.3889/seejim.2017.20011

Keywords:

antioxidants, carbocysteine, questionnaire, spirometry stable COPD

Abstract

BACKGROUND: The recent epidemiological and experimental evidence suggest possible antioxidant effect of carbocysteine in patients with chronic obstructive pulmonary disease (COPD).

AIM: To assess efficacy and tolerability of carbocysteine in the management of stable COPD.

METHODS: We performed an observational, non-randomized, open study (a real life study) including 87 patients with stable COPD (group B and D by combined COPD assessment) divided in two groups, examined group (EG) and control group (CG). All participants were treated with the regular treatment of the stable disease, but in the participants of the EG carbocysteine 1,500 mg daily was added to their regular treatment during the period of two months. The study protocol included completion of the COPD Assessment Test (CAT) and spirometric measurements at initial visit and at the end of the mentioned period.

RESULTS: We found significantly lower mean value of the overall CAT score in the EG at the end of the study as compared to its mean value registered at initial visit (26.9 vs. 24.3; P = 0.007). In regard to certain CAT items, we found significantly lower values of the mean scores related to cough phlegm and sleep disturbances as compared to their mean scores at initial visit. In addition, the mean values of the overall CAT scores at initial visit and at the end of the study in controls were similar. In EG we found significantly higher mean value of the MEF 25-75 at the end of the study as compared to its mean value registered at initial visit (59.3% vs. 67.2%; P = 0.003). There was no significant difference in the mean values of other spirometric parameters at the end of the study as compared to their mean values at initial visit. In controls we registered similar values of all measured spirometric parameters at the end of the study as compared to their values registered at initial visit. Mild gastrointestinal manifestations were registered in 13.3% of the participants of the EG during the examined period.

CONCLUSION: Our findings indicate positive effects of carbocysteine regarding the symptoms and lung function, as well as its good tolerability in the patients with stable COPD.

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Author Biography

Jordan Minov, Institute for Occupational Health of Republic of Macedonia, Skopje – WHO Collaborating Center, Skopje

Personal data

Date of birth: 9 July 1960

Home address: Vladimir Komarov 16-1/7, 1000 Skopje, R. Macedonia

Office address: Institute of Occupational Health of R. Macedonia - WHOCollaborativeCenter and GA2LEN Collaborative Center, II Makedonska brigada 43, 1000 Skopje, R. Macedonia

Tel: + 389 2 2461 387

Fax: + 389 2 2621 428

E-mail: minovj@hotmail.com

 

Education and key qualifications

"¢ Specialist in internal medicine

"¢ Specialist in occupational medicine

"¢ Subspecialist in pulmonology and allergology

 

Present appointment

"¢ Head of the Department for Physiology of Work at the Institute for Occupational Health of R. Macedonia – WHO Collaborative Centre and GA2LEN Collaborative Centre

"¢ Professor at the Medical Faculty, University "St. Cyril and Methodius" Skopje

 

Scientific field of interest

"¢ Chronic obstructive airway diseases, functional lung diagnostics, occupationally-related respiratory and allergic diseases

 

Research activities

"¢ Researcher (co-operator) of the long-term scientific project funded by Ministry of Education and Science "Epidemiology of Allergic Rhinitis in the Republic of Macedonia in Correlation with Pollen Microflora" (2001-2003);

"¢ Co-operator of the Regional HESME Workshop "Work-Related Diseases" (June 2003);

"¢ Investigator in a phase III, parallel, comparative, partially blinded, placebo-controlled study on the efficacy and safety of FORMOTEROL SMB AXAHALERR DPI 12 mg and FORADILR AEROLIZERR DPI 12 mg in patients with moderate persistent asthma sponsored by Laboratoires SMB S.A. Belgium (November 2006 – May 2007);

"¢ Investigator in a phase III, randomized, parallel group study on the efficacy and safety of SMB BUDESONIDE-SALMETEROL DPI capsule 150/25μg BID delivered by the AXAHALER® versus SYMBICORT® TURBUHALER® 200/12μg BID in patients with moderate to severe persistent asthma (February 2009-March 2010);

"¢ Researcher in the GA2LEN survey and Survey Follow up Study from the Skopje centre (November 2007 – August 2010);

"¢ Nominated represent by Ministry of Health of R. Macedonia in the activities of the WHO Regional Office for Europe aimed at the development of national programmes for the elimination of asbestos-related diseases (ARDs) (June 2011-to date);

"¢ Member of the Management Committee of the COST Action TDI 1206 Development and Implementation of European Standards on Prevention of Occupational Skin Diseases (StanDerm);    

"¢ Investigator in a HZC113782: A Clinical Outcomes Study to compare the effect of Fluticasone Furoate/Vilanterol Inhalation Powder 100/25mcg with placebo on Survival in Subjects with Moderate Chronic Obstructive Pulmonary Disease (COPD) and a history of or at increased risk for cardiovascular disease (March 2012 – to date).

 

Member of Editorial Boards

"¢ Member of the Editorial Board of the American Journal of Immunology and Global Journal of Allergy

 

Publications

"¢ Member of the Editorial Board and one of the authors of the monograph "Allergic Diseases in R. Macedonia", ed. V. Cvetanov; Skopje, 2006

"¢ Author of the monograph "Lung and Pleural Diseases Related to Occupational Exposures"; Skopje, 2009

"¢ Author of the monograph "Spirometry"; Skopje 2010

"¢ One of the authors of the monograph "Occupational Medicine", ed. J. Karadzinska-Bislimovska; Skopje 2011

"¢ Author of the monograph "Smoking among Macedonian Workers"; Saarbrí¼cken 2013

"¢ Author and co-author of more than 150 papers published in domestic and international journals

 

Memberships

International: European Respiratory Society, EuropeanAcademy of Allergology and Clinical Immunology, World Allergy Organization

National: Macedonian Respiratory Society, Macedonian Society of Basic and Clinical Immunology and Allergology, Macedonian Society of Occupational Medicine Specialists

 

 Languages spoken: English (fluent), German (less fluent)

 

Computer Literacy: Good

References

Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PloS Med. 2006; 3: e442. https://doi.org/10.1371/journal.pmed.0030442 PMid:17132052 PMCid:PMC1664601

European Respiratory Society. European Lung White Book: Huddersfield, European Respiratory Society Journals Ltd; 2003.

Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease: 2014 Update. Available at: http://www.goldcopd.org/ (Accessed 04.08.2016).

Global Initiative for Chronic Obstructive Pulmonary Disease. A pocket guide to COPD diagnosis, management and prevention: Updated 2015. Available at: http://www.goldcopd.org/ (Accessed 04.08.2016).

Carbocisteine. Available at: www.mhra.gov.uk (Accessed 24.07.2016).

Moretti M, Bottrighi P, Dallari R, et al. The effect of long-term treatment with erdosteine on chronic obstructive pulmonary disease: the EQUALIFE Study. Drugs Exp Clin Res. 2004; 30: 143-152. PMid:15553660

van Overveld FJ, Demkow U, Gorecka D, et al. New developments in the treatment of COPD: comparing the effects of inhaled corticosteroids and N-acetylcysteine. J Physiol Pharmacol. 2005; 56: 135-142. PMid:16204787

Poole P, Black PN. Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2010; CD001287. https://doi.org/10.1002/14651858.CD001287.pub3

World Health Organization. Guidelines for controlling and monitoring the tobbaco epidemic. Geneva: WHO, 1998.

U.S. Department of Health and Human Services. The health consequences of smoking: chronic obstructive pulmonary disease. A report of the Surgeon General. US Department of Health and Human Services, Public Health Service, Office of the Assistant for Health, Office of Smoking and Health. DHHS Publication No. 84-50 205, 1984.

Janson C, Chinn S, Jarvis D, et al. Effects of passive smoking on respiratory symptoms, bronchial responsiveness, lung function, and total serum IgE in the European Community Respiratory Health Survey: a cross-sectional study. Lancet. 2001; 358: 2103-2109. https://doi.org/10.1016/S0140-6736(01)07214-2

COPD Assessment Test. Available at: www.CATestonline.org (Accessed 12.09.2016).

Spirometry Guide: 2010 Update. Available at: http://www.goldcopd.org/uploads/users/files/GOLD_Spirometry_2010. (Accessed 15.07.2016).

Miller MR, Hankinson J, Brusasco V, et al. Standardisation of spirometry. Eur Respir J. 2005; 26: 319-338. https://doi.org/10.1183/09031936.05.00034805 PMid:16055882

Rahman I. Antioxidant therapies in COPD. Int J Chron Obstruct Pulmon Dis. 2006 ; 1 (1) : 15-29. https://doi.org/10.2147/copd.2006.1.1.15

Maccio A, Madeddu C, Panzone F, Mantovani G. Carbocysteine: clinical experience and new perspectives in the treatment of chronic inflammatory diseases. Expert Opin Pharmacother. 2009; 10 (4): 693-793. https://doi.org/10.1517/14656560902758343 PMid:19239402

Biswas S, Hwang JW, Kirkham PA, Rahman I. Pharmacological and dietary antioxidant therapies for chronic obstructive pulmonary disease. Curr Med Chem. 2013; 20 (12): 1496-1530. https://doi.org/10.2174/0929867311320120004 PMid:22963552

Bradolini L, Allegretti M, Berdini V, et al. Carbocysteine lysine salt monohydrate (SCMC-Lys) is a selective scavenger of reactive oxygen intermediates (ROIs). Eur Cytokine Netw. 2003; 14: 20-26.

Rahman I, Kitty I. Antioxidant therapeutic targets in COPD. Curr Drug Targets. 2006; 7 (6): 707-720. https://doi.org/10.2174/138945006777435254 PMid:16787173

Hooper C, Calvert J. The role for S-carboxymethylcysteine (carbocysteine) in the management of chronic obstructive pulmonary disease. Int J COPD. 2008; 3 (4): 659-669.

Rahman I, McNee W. Antioxidant pharmacological therapies for COPD. Curr Opin Pharmacol. 2012; 12 (3): 256-265. https://doi.org/10.1016/j.coph.2012.01.015 PMid:22349417 PMCid:PMC3768007

Leicestershire Medicines Strategy Group. Medicines management of stable COPD. Available at: www.lmsg.nhs.uk/guidelines (Accessed 18.07.2016).

Minov J, Karadzinska-Bislimovska J, Nelovska Z, Vasilevska K, Risteska-Kuc S, Stoleski S, Mijakoski D. Smoking among Macedonian workers five years after anti-smoking campaign. Arh Hig Rada Toksikol. 2012; 63: 207-213. https://doi.org/10.2478/10004-1254-63-2012-2150 PMid:22728803

Minov J. Smoking among Macedonian Workers. Saarbrí¼cken: LAP LAMBERT Academic Publishing, 2013.

Tobacco Surveillance Data Brief: Adult Cigarette Smoking Prevalence. Available at: http://www.state.nj.us/health/as/ctcp/documents. (Accessed 21.07.2016).

South Australian smoking prevalence by industry and occupation. Available at: www.cancersa.org.au/ (Accessed 21.07.2016).

Zheng JP, Kang J, Huang SG, et al. Effect of carbocysteine on acute exacerbations of chronic obstructive pulmonary disease (PEACE study): a randomized placebo-controlled study. Lancet. 2008; 371: 2013-2018. https://doi.org/10.1016/S0140-6736(08)60869-7

Yasuda H, Yamaya M, Sasaki T, et al. Carbocysteine reduces frequency of common colds and exacerbations in patients with chronic obstructive pulmonary disease. J Am Geriatr Soc. 2006; 54: 378-380. https://doi.org/10.1111/j.1532-5415.2005.00592_9.x PMid:16460403

Tatsumi K, Fukuchi Y. Carbocysteine improves quality of life in chronic obstructive pulmonary disease. J Am Geriatr Soc. 2007; 55: 1884-1886. https://doi.org/10.1111/j.1532-5415.2007.01373.x PMid:17979906

Esposito A, Valentino MR, Bruzzese D, et al. Effect of carbocysteine in prevention of exacerbation of chronic obstructive pulmonary disease (CAPRI study): an observational study. Pulmonary Pharmacology & Therapeutics. 2016: 37: 85-88. https://doi.org/10.1016/j.pupt.2016.03.003 PMid:26970503

Pace E, Ferraro M, Di Vincenzo S, et al. Comparative cytoprotective effects of carbocysteine and fluticasone propionate in cigarette smoke extract-stimulated bronchial epithelial cells. Cell Stress and Chaperones. 2013; 18: 733-743. https://doi.org/10.1007/s12192-013-0424-0 PMid:23580157 PMCid:PMC3789875

Song Y, Lu H-Z, Xu J-R, et al. Carbocysteine restores steroid sensitivity by targeting histone deacetylase 2in a thiol/GSH dependent manner. Pharmacological Research. 2015; 91: 88-98. https://doi.org/10.1016/j.phrs.2014.12.002 PMid:25500537

Decramer M, Rutten-van Molken M, Dekhuijzen SG, et al. Effects of N-acetylcysteine in outcomes of chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomized, placebo-controlled trial. Lancet. 2005; 365: 1552-1560. https://doi.org/10.1016/S0140-6736(05)66456-2

Tse HN, Raiteri L, Wong KY, 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. https://doi.org/10.1378/chest.12-2357 PMid:23348146

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Published

2017-12-27

Issue

Section

Clinical Immunology