Experience of use and perspectives of carbocysteine in respiratory tract pathology treatment


DOI: https://dx.doi.org/10.18565/therapy.2024.3.94-102

Vertkin A.L., Knorring G.Yu., Shamuilova M.M.

Russian University of Medicine of the Ministry of Healthcare of Russia, Moscow
Abstract. Medical statistics accepts respiratory system diseases to be the most common in the structure of morbidity in Russia; also they are leading in the number of cases of associated disability. Most of these diseases are acute respiratory viral infections (ARVI) and bronchitis. The causes and mechanisms of respiratory tract damage due to viral infections are varied and require the use of a wide range of medications. Using of mucoactive agents in these cases is justified by their most important characteristics. Thus, carbocisteine, in addition to its mucoregulatory, mucolytic activities and the ability to improve mucociliary transportation, also demonstrates anti-inflammatory, immunomodulatory and antioxidant properties, which determines its place in the treatment of acute respiratory viral infections and bronchitis. The article provides a review of studies on the efficacy of this mucoactive medicine and also outlines perspectives for its use in therapeutic practice.

Literature


1. О состоянии санитарно-эпидемиологического благополучия населения в Российской Федерации в 2016 году: государственный доклад. Федеральная служба по надзору в сфере защиты прав потребителей и благополучия человека. М. 2017: 220 с. Доступ: https://www.rospotrebnadzor.ru/documents/details.php?ELEMENT_ID=8345 (дата обращения – 01.03.2024). (On the state of sanitary and epidemiological well-being of the population in the Russian Federation in 2016: state report. Federal Service for Supervision of Consumer Rights Protection and Human Welfare. Moscow. 2017: 220 pp. URL: https://www.rospotrebnadzor.ru/documents/details.php?ELEMENT_ID=8345 (date of access – 01.03.2024) (In Russ.)).


2. Грипп. ВОЗ. 2018. Доступ: https://www.who.int/ru/news-room/factsheets/detail/influenza-(seasonal) (дата обращения – 01.10.2021). (Influenza. World Health Organization. 2018. URL: https://www.who.int/ru/news-room/factsheets/detail/influenza-(seasonal) (date of access – 01.10.2021) (In Russ.)).


3. Ющук Н.Д., Хадарцев О.С. Профилактика гриппа и острых респираторных вирусных инфекций с учетом особенности их эпидемического процесса. Инфекционные болезни: новости, мнения, обучение. 2018; 7(2): 44–51. (Yushchuk N.D., Khadartsev O.S. Prevention of influenza and acute respiratory viral infections and their epidemic process characteristics. Infektsionnyye bolezni: novosti, mneniya, obucheniye = Infectious Diseases: News, Views, Education. 2018; 7(2): 44–51 (In Russ.)).


https://doi.org/10.24411/2305-3496-2018-12004. EDN: XQCWSL.


4. Колбин А.С., Гомон Ю.М., Балыкина Ю.Е. с соавт. Социально-экономическое и глобальное бремя COVID-19. Качественная клиническая практика. 2021; (1): 24–34. (Kolbin A.S., Gomon Yu.M., Balykina Yu.E. et al. Socioeconomic and global burden of COVID-19. Kachestvennaya klinicheskaya praktika = Good Clinical Practice. 2021; (1): 24–34 (In Russ.)).


https://doi.org/10.37489/2588-0519-2021-1-24-34. EDN: UEICPL.


5. Сафина А.И., Выжлова Е.Н., Малиновская В.В. Сложности диагностики и лечения острых респираторных инфекций у детей в сезон «тридемии». Вопросы практической педиатрии. 2023; 18(2): 111–115. (Safina A.I., Vyzhlova E.N., Malinovskaya V.V. Difficulties in diagnosing and treating acute respiratory infections in children during the “tridemic” season. Voprosy prakticheskoy pediatrii = Issues of Practical Pediatrics. 2023; 18(2): 111–115 (In Russ.)).


https://doi.org/10.20953/1817-7646-2023-2-111-115. EDN: RBUQMT.


6. Верткин А.Л., Дудина К.Р., Носова А.В. Портрет пациента с инфекционной патологией. Инфекционные болезни: новости, мнения, обучение. 2020; 9(3): 120–123. (Vertkin A.L., Dudina K.R., Nosova A.V. Portrait of a patient with an infectious pathology. Infektsionnyye bolezni: novosti, mneniya, obucheniye = Infectious Diseases: News, Views, Education. 2020; 9(3): 120–123 (In Russ.)).


https://doi.org/10.33029/2305-3496-2020-9-3-88-95. EDN: CSUBSA.


7. Кулагина М.Г., Верткин А.Л., Зайратьянц О.В., Носова А.В. Ключевые признаки инфекционной патологии, протекающей с поражением респираторного тракта. Инфекционные болезни: новости, мнения, обучение. 2021; 10(1): 79–88. (Kulagina M.G., Vertkin A.L., Zayratyants O.V., Nosova A.V. Key signs of infectious pathology, those proceeds with the defeat of the respiratory tract. Infektsionnyye bolezni: novosti, mneniya, obucheniye = Infectious Diseases: News, Views, Education. 2021; 10(1): 79–88 (In Russ.)).


https://doi.org/10.33029/2305-3496-2021-10-1-79-88. EDN: HZDLZF.


8. Клячкина И.Л., Рыбаченко В.В., Кнорринг Г.Ю., Воронина Е.В. Опыт и перспективы системной энзимотерапии при лечении заболеваний дыхательных путей. Доктор.Ру. 2006; (2): 31–35. (Klyachkina I.L., Rybachenko V.V., Knorring G.Yu., Voronina E.V. Experience and prospects of systemic enzyme therapy in the treatment of respiratory diseases. Doctor.Ru. 2006; (2): 31–35 (In Russ.)). EDN: PUPHJX.


9. Верткин А.Л., Прохорович Е.А., Намазова Л.С. с соавт. Оптимизация эмпирической терапии внебольничной пневмонии у больных пожилого и старческого возраста. РМЖ. 2002; 10(16): 708–712. (Vertkin A.L., Prokhorovich E.A., Namazova L.S. et al. Optimization of empiric therapy for community-acquired pneumonia in elderly and senile patients. Russkiy meditsinskiy zhurnal = Russian Medical Journal. 2002; 10(16): 708–712 (In Russ.)). EDN: VZHDXA.


10. Зайцев А.А. Кашель: проблемы и решения. Практическая пульмонология. 2020; (2): 78–86. (Zaitsev A.А. Cough: Problems and solutions. Prakticheskaya pulmonologiya = Practical Pulmonology. 2020; (2): 78–86 (In Russ.)). EDN: INXNII.


11. Рябова М.А. Актуальность применения мукоактивных препаратов при кашле разного этиопатогенеза в период пандемии COVID-19. Эффективная фармакотерапия. 2020; 16(34): 20–25. (Ryabova M.A. Relevance of the use of mucoactive drugs for coughing with different etiopathogenesis during the COVID-19 pandemic. Effektivnaya farmakoterapiya = Effective Pharmacotherapy. 2020; 16(34): 20–25 (In Russ.)).


https://doi.org/10.33978/2307-3586-2020-16-34-20-25. EDN: OIGGIR.


12. Казанцев В.А. Мукоактивная терапия при лечении больных с инфекциями нижних дыхательных путей. Медицинский совет. 2015; (16): 83–89. (Kazantsev V.A. Mucoactive therapy in the treatment of patients with lower respiratory tract infections. Meditsinskiy sovet = Medical Council. 2015; (16): 83–89 (In Russ.)). EDN: UNTMVT.


13. Бережной В.В., Гляделова Н.П. Мукорегуляторные препараты в терапии кашля при респираторной патологии у детей (обзор литературы). Современная педиатрия. 2015; (8): 57. (Berezhnoi V.V., Glyadelova N.P. Mukoregulative preparations in the treatment of cough due to the respiratory tract diseases in children (literature review). Sovremennaya pediatriya = Modern Pediatrics. 2015; (8): 57 (In Russ.)). EDN: VLCTIN.


14. Клячкина И.Л., Белоцерковская Ю.Г., Романовских А.Г. Мукорегуляторы в программе лечения острой респираторной вирусной инфекции. РМЖ. 2018; 26(3–1): 14–18. (Klyachkina I.L., Belotserkovskaya Yu.G., Romanovskikh A.G. Mucoregulators in the treatment of acute respiratory viral infection. Russkiy meditsinskiy zhurnal = Russian Medical Journal. 2018; 26(3–1): 14–18 (In Russ.)). EDN: YVMOVD.


15. Duijvestijn Y.C., Mourdi N., Smucny J. et al. Acetylcysteine and carbocysteine for acute upper and lower respiratory tract infections in paediatric patients without chronic broncho-pulmonary disease. Cochrane Database Syst Rev. 2009; 21(1): CD003124.


https://doi.org/10.1002/14651858.CD003124.pub4. PMID: 23728642.


16. Синопальников А.И., Клячкина И.Л. Кашель. М.: Медицинское информационное агентство. 2013; с. 118–119, 128–129. (Sinopalnikov A.I., Klyachkina I.L. Cough. Moscow: Medical Information Agency. 2013: 118–119, 128–129 pp. (In Russ.)). ISBN: 978-5-9986-0148-4.


17. Оковитый С.В., Зайцев А.А., Анисимова Н.А. Фармакодинамические подходы к применению мукоактивных препаратов. Лечащий врач. 2020; (10): 6–10. (Okovityi S.V., Zaitsev A.A., Anisimova N.A. Pharmacodynamic approaches to the use of mucoactive drugs. Lechaschiy vrach = Attending Physician. 2020; (10): 6–10 (In Russ.)).


https://doi.org/10.26295/OS.2020.62.62.001. EDN: CNBKRI.


18. Бабак С.Л., Горбунова М.В., Малявин А.Г. Муцины и карбоцистеин: защита дыхательных путей. Терапия. 2021; 7(10): 160–168. (Babak S.L., Gorbunova M.V., Malyavin A.G. Mucins and carbocisteine: respiratory protection. Terapiya = Therapy. 2021; 7(10): 160–168 (In Russ.)).


https://doi.org/10.18565/therapy.2021.10.160-168. EDN: JTAWPA.


19. Верткин А.Л., Шамуилова М.М., Кнорринг Г.Ю. Место карбоцистеина при лечении ОРВИ и бронхита в терапевтической практике. Лечащий врач. 2023; 26(3): 52–57. (Vertkin А.L., Shamuilova M.M., Knorring G.Yu. Place of carbocysteine in the treatment of acute respiratory viral infections and bronchitis in therapeutic practice. Lechaschiy vrach = Attending Physician. 2023; 26(3): 52–57 (In Russ.)).


https://doi.org/10.51793/OS.2023.26.3.009. EDN: QJMEBD.


20. Мизерницкий Ю.Л., Мельникова И.М. Место карбоцистеина в амбулаторной педиатрической практике. Лечащий врач. 2018; (9): 42–45. (Mizernitsky Yu.L., Melnikova I.M. The place of carbocysteine in outpatient pediatric practice. Lechaschiy vrach = Attending Physician. 2018; (9): 42–45 (In Russ.)). EDN: VGNFVI.


21. (Havez R., Degand P., Roussel P. et al. Biochemical mode of action of cysteine by-products on the bronchial mucus. Poulmon Coeur. 1970; 26(1): 81–90 (In French)). PMID: 5421538.


22. Maccio A., Madeddu C., Panzone F. et al. Carbocysteine: Clinical experience and new perspectives in the treatment of chronic inflammatory diseases. Expert Opin Pharmacother. 2009; 10(4): 693–703.


https://doi.org/10.1517/14656560902758343. PMID: 19239402.


23. Рязанцев С.В. Роль Флюдитека (карбоцистеина) в муколитической терапии верхних дыхательных путей и уха. Российская оториноларингология. 2005; (1): 117–119. (Ryazantsev S.V. The role of Fluditec (Carbocisten) in mucolytic therapy of the upper respiratory tract and ear. Rossiyskaya otorinolaringologiya = Russian Otorhinolaryngology. 2005; (1): 117–119 (In Russ.)). EDN: GMRCUO.


24. Chang A.B. Widdicombe J.G. Cough throughout life: Children, adults and the senile. Pulm Pharmacol Ther. 2007; 20(4): 371–82.


https://doi.org/10.1016/j.pupt.2006.10.004. PMID: 17118685.


25. Nogawa H., Ishibashi Y., Ogawa A. et al. Carbocisteine can scavenge reactive oxygen species in vitro. Respirology. 2009; 14(1): 53–59.


https://doi.org/10.1111/j.1440-1843.2008.01424.x. PMID: 19144049.


26. Wang W., Guan W., Huang R.-Q. et al. Carbocisteine attenuates TNF-α-induced inflammation in human alveolar epithelial cells in vitro through suppressing NF-κB and ERK1/2 MAPK signaling pathways. Acta Pharmacol Sin. 2016; 37(5): 629–36.


https://doi.org/10.1038/aps.2015.150. PMID: 26997568. PMCID: PMC4857541.


27. Шуганов Е.Г., Салмаси Ж.М., Шуганов А.Е. Клинико-иммунологические эффекты карбоцистеина при лечении больных хронической обструктивной болезнью легких. Альманах клинической медицины. 2014; (35): 66–70. (Shuganov E.G. Salmasi Zh.M. Shuganov A.E. Clinical and immunological effects of carbocysteine in chronic obstructive pulmonary disease. Al’manakh klinicheskoy meditsiny = Almanac of Clinical Medicine. 2014; (35): 66–70 (In Russ.)). EDN: TFKLWH.


28. 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 Chaperones. 2013; 18(6): 733–43.


https://doi.org/10.1007/s12192-013-0424-0. PMID: 23580157. PMCID: PMC3789875.


29. Yamaya M. Nishimura H., Shinya K. Inhibitory effects of carbocisteine on type A seasonal influenza virus infection in human airway epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2010; 299(2): 160–68.


https://doi.org/10.1152/ajplung.00376.2009. PMID: 20543005.


30. Yasuda H., Yamaya M., Sazaki T. et al. Carbocysteine inhibits rhinovirus infection in human tracheal epithelial cells. Eur Respir J. 2006; 28(1): 51–58.


https://doi.org/10.1183/09031936.06.00058505. PMID: 16510461.


31. Sumitomo T., Nakata M., Yamaguchi M. et al. Сarboxymethylcysteine inhibits adherence of Streptococcus pneumoniae to human alveolar epithelial cells. J Med Microbiol. 2012; 61(Pt 1): 101–8.


https://doi.org/10.1099/jmm.0.033688-0. PMID: 21890513.


32. Suer E., Sayrac S., Sarinay E. et al. Variation in attachment of Streptococcus pneumoniae to human pharyngeal epithelial cells after treatment with S+carboxymethylcysteine. J Infect Chemother. 2008; 14(4): 333–36.


https://doi.org/10.1007/s10156-008-0626-z. PMID: 18709541.


33. Asada M., Yoshida M., Hatachi Y. Сarbocisteine inhibits respiratory syncytial virus infection in human tracheal epithelial cells. Respir Physiol Neurobiol. 2012; 180(1): 112–18.


https://doi.org/10.1016/j.resp.2011.10.017. PMID: 22080978.


34. (Chezzi G.L., Zanocco P., Arrigoni G. Valutazione control-lata di un mucoregolatore, la carbocisteina, in un gruppo di pazzi-enti affetti da rinopatie chroniche catarrali. La Carbocisteina Oggi. Septembre, 1987 (In Italian)).


35. (Catalano G.B., Mallanino N., Serra A. La carbocisteina nella patologia flogistica cronica rinosinusale. Otorinolaringologia. 1981; 31: 1–11 (In Italian)).


36. (Spingo G., Teatini G.P. Valutazione dell’efficacia della carbocisteina nel trattamentodelle otiti catarrali. Oto Rino Laring. 1981; 31: 1–4 (In Italian)).


37. Kumasava Т., Ushiro K. Clinical evaluation of S-CMC syrup applied in the treatment of otitis media with effusion. Double blind comparative test with placebo. Acta Otolaringol (Stockh). 1988; 458: 56–62.


https://doi.org/10.3109/00016488809125103. PMID: 3072830.


38. (Spingo G., Teatini G.P. L’impiego di un mucolitico orale nel trattamento dell otiti sieromucose. Nuevo Arch Ital. 1977; 5: 115–22 (In Italian)).


39. Majima Y., Kurono Y., Hirakawa K. et al. Efficacy of combined treatment with S-carboxymethylcysteine (carbocisteine) and clarithromycin in chronic rhinosinusitis patients without nasal polyp or with small nasal polyp. Auris Nasus Larynx. 2012; 39(1): 38–47.


https://doi.org/10.1016/j.anl.2011.04.015. PMID: 21636230.


40. Овчинников А.Ю., Панякина М.А. Положительный опыт комплексного консервативного лечения острого и хронического гайморита в стадии обострения. Эффективная фармакотерапия. 2010; (27): 84–91. (Ovchinnikov A.Yu., Panyakina M.A. Positive experience of complex conservative treatment of acute and chronic sinusitis in the acute stage. Effektivnaya farmakoterapiya = Effective Pharmacotherapy. 2010; (27): 84–91 (In Russ.)). EDN: SHRPIJ.


41. Тарасова Г.Д. Влияние Флюдитека на воспаление полости носа. Российская ринология. 2005; (2): 201. (Tarasova G.D. Effect of Fluditec on inflammation of the nasal cavity. Rossiyskaya rinologiya = Russian Rhinology. 2005; (2): 201 (In Russ.)). EDN: HSBENV.


42. Тарасова Г.Д., Иванова Т.В., Протасов П.Г. Флюдитек в лечении воспалительных заболеваний верхних дыхательных путей. Российская оториноларингология. 2005; (6): 77–81. (Tarasova G.D., Ivanova T.V., Protasov P.G. Fluditec in the treatment of inflammatory diseases of the upper respiratory tract. Rossiyskaya otorinolaringologiya = Russian Otorhinolaryngology. 2005; (6): 77–81 (In Russ.)). EDN: VJFGUD.


43. Балясинская Г.Л., Люманова С.Р., Ланда Р.И. Значение мукоактивной терапии в лечении острых синуситов у детей. Российская оториноларингология. 2006; (6): 84–86. (Balyasinskaya G.L., Lyumanova S.R., Landa R.I. Significance of mucoactive therapy in the treatment of acute sinusitis in children. Rossiyskaya otorinolaringologiya = Russian Otorhinolaryngology. 2006; (6): 84–86 (In Russ.)). EDN: HVMLML.


44. Allegra L., Cordaro C.I., Grassi C. Prevention of acute exacerbations of chronic obstructive bronchitis with carbocysteine lysine salt monohydrate: A multicenter, double-blind, placebo-controlled trial. Respiration. 1996; 63(3): 174–80.


https://doi.org/10.1159/000196540. PMID: 8739489.


45. Tatsumi K., Fukuchi Y. Carbocysteine improves quality of life in patients with chronic obstructive pulmonary disease. J Am Geriatr Soc. 2007; 55(11): 1884–86.


https://doi.org/10.1111/j.1532-5415.2007.01373.x. PMID: 17979906.


46. 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(2): 378–80.


https://doi.org/10.1111/j.1532-5415.2005.00592_9.x. PMID: 16460403.


47. Zheng J.P., Kang J., Huang S.G. et al. Effect of carbocysteine on acute exacerbation of chronic obstructive pulmonary disease (PEACE Study): A randomized placebo-controlled study. Lancet. 2008; 371(9629): 2013–18.


https://doi.org/10.1016/S0140-6736(08)60869-7. PMID: 18555912.


48. Chalumeau M., Duijvestijn Y.C. Acetylcysteine and carbocysteine for acute upper and lower respiratory tract infections in paediatric patients without chronic broncho-pulmonary disease. Cochrane Database Syst Rev. 2013; (5): CD003124.


https://doi.org/10.1002/14651858.CD003124.pub4. PMID: 23728642.


49. Konradova V., Vavrova V., Sulova J. Comparison of the effect of three oral mucolytics on the ultrastructure of the tracheal epithelium in rabbits. Respiration. 1985; 48(1): 50–57.


https://doi.org/10.1159/000194798. PMID: 3927460.


50. Cazzola M., Rogliani P., Calzetta L. et al. Impact of mucolytic agents on COPD exacerbations: A pair-wise and network meta-analysis. COPD. 2017; 14(5): 552–63.


https://doi.org/10.1080/15412555.2017.1347918. PMID: 28753070.


51. Rogliani P., Matera M.G., Page C. et al. Efficacy and safety profile of mucolytic/antioxidant agents in chronic obstructive pulmonary disease: A comparative analysis across erdosteine, carbocysteine, and N-acetylcysteine. Respir Res. 2019; 20(1): 104.


https://doi.org/10.1186/s12931-019-1078-y. PMID: 31133026. PMCID: PMC6537173.


52. Papi A., Avdeev S., Calverley P.M.A. et al. Use of mucolytics in COPD: A Delphi consensus study. Respir Med. 2020; 175: 106190.


https://doi.org/10.1016/j.rmed.2020.106190. PMID: 33217537.


53. Клинические рекомендации. Хронический бронхит. Российское респираторное общество. Рубрикатор клинических рекомендаций Минздрава России. 2021. ID: 655. Доступ: https://cr.minzdrav.gov.ru/schema/655_1 (дата обращения – 01.03.2024). (Clinical guidelines. Chronical bronchitis. Russian Respiratory Society. Rubricator of clinical guidelines of the Ministry of Healthcare of Russia. 2021. ID: 655. URL: https://cr.minzdrav.gov.ru/schema/655_1 (date of access – 01.03.2024) (In Russ.)).


54. Клинические рекомендации. Хроническая обструктивная болезнь легких. Российское респираторное общество. Рубрикатор клинических рекомендаций Минздрава России. 2021. ID: 603. Доступ: https://cr.minzdrav.gov.ru/schema/603_2 (дата обращения – 01.03.2024). (Clinical guidelines. Chronic obstructive pulmonary disease. Russian Respiratory Society. Rubricator of clinical guidelines of the Ministry of Healthcare of Russia. 2021. ID: 603. URL: https://cr.minzdrav.gov.ru/schema/603_2 (date of access – 01.03.2024) (In Russ.)).


55. Клинические рекомендации. Острый синусит. Национальная медицинская ассоциация оториноларингологов. Рубрикатор клинических рекомендаций Минздрава России. 2021. ID: 313. Доступ: https://cr.minzdrav.gov.ru/schema/313_2 (дата обращения – 01.03.2024). (Clinical guidelines. Acute sinusitis. National Medical Association of Otolaryngologists. Rubricator of clinical guidelines of the Ministry of Healthcare of Russia. 2021. ID: 313. URL: https://cr.minzdrav.gov.ru/schema/313_2 (date of access – 01.03.2024) (In Russ.)).


About the Autors


Arkadiy L. Vertkin, MD, Dr. Sci. (Medicine), professor, head of the Department of therapy, clinical pharmacology and emergency medical care of the Faculty of general medicine of N.A. Semashko Research and Educational Institute of Clinical Medicine, Russian University of Medicine. Address: 127006, Moscow, 4 Dolgorukovskaya St.
E-mail: kafedrakf@mail.ru
ORCID: https://orcid.org/0000-0001-8975-8608
German Yu. Knorring, MD, PhD (Medicine), associate professor of the Department of therapy, clinical pharmacology and emergency medical care of the Faculty of general medicine of N.A. Semashko Research and Educational Institute of Clinical Medicine, Russian University of Medicine. Address: 127006, Moscow, 4 Dolgorukovskaya St.
E-mail: knorring@mail.ru
ORCID: https://orcid.org/0000-0003-4391-2889
Marina M. Shamuilova, MD, Dr. Sci. (Medicine), professor of the Department of therapy, clinical pharmacology and emergency medical care of the Faculty of general medicine of N.A. Semashko Research and Educational Institute of Clinical Medicine, Russian University of Medicine. Address: 127006, Moscow, 4 Dolgorukovskaya St.
E-mail: kafedrakf@mail.ru


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