Mucoactive drugs in the treatment of respiratory diseases in children

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

The formation of mucus in the airways is the first line of defense against microbial agents, allergens, and foreign particles. However, excessive sputum production and difficulty in clearing the airways can lead to many respiratory diseases. Mucoactive substances are drugs that either change the properties of sputum or reduce its production. The article provides a brief overview of common mucoactive agents, as well as current data on the main therapeutic effects of ambroxol.

Full Text

Restricted Access

About the authors

Marina D. Shakhnazarova

Sechenov University

Author for correspondence.
Email: marinashakh@mail.ru
ORCID iD: 0000-0003-3512-5455

Cand. Sci. (Med.), Associate Professor at the Department of Children’s Diseases, Clinical Institute of Children’s Health n.a. N.F. Filatov

Russian Federation, Moscow

N. A. Geppe

Sechenov University

Email: marinashakh@mail.ru
ORCID iD: 0000-0003-0547-3686

Department of Children’s Diseases, Clinical Institute of Children’s Health n.a. N.F. Filatov

Russian Federation, Moscow

I. V. Ozerskaya

Sechenov University

Email: marinashakh@mail.ru
ORCID iD: 0000-0001-6062-5334

Department of Children’s Diseases, Clinical Institute of Children’s Health n.a. N.F. Filatov

Russian Federation, Moscow

I. V. Grebeneva

Sechenov University

Email: marinashakh@mail.ru
ORCID iD: 0000-0001-5523-5323

Department of Children’s Diseases, Clinical Institute of Children’s Health n.a. N.F. Filatov

Russian Federation, Moscow

N. G. Kolosova

Sechenov University

Email: marinashakh@mail.ru

Department of Children’s Diseases, Clinical Institute of Children’s Health n.a. N.F. Filatov

Russian Federation, Moscow

S. I. Shatalina

Sechenov University

Email: marinashakh@mail.ru
ORCID iD: 0000-0003-2085-0021

Department of Children’s Diseases, Clinical Institute of Children’s Health n.a. N.F. Filatov

Russian Federation, Moscow

E. V. Frolkova

Sechenov University

Email: marinashakh@mail.ru
ORCID iD: 0000-0002-3158-1819

Department of Children’s Diseases, Clinical Institute of Children’s Health n.a. N.F. Filatov

Russian Federation, Moscow

O. V. Batyreva

Sechenov University

Email: marinashakh@mail.ru

Department of Children’s Diseases, Clinical Institute of Children’s Health n.a. N.F. Filatov

Russian Federation, Moscow

S. E. Fidanyan

Sechenov University

Email: marinashakh@mail.ru
ORCID iD: 0000-0001-9592-3542

Department of Children’s Diseases, Clinical Institute of Children’s Health n.a. N.F. Filatov

Russian Federation, Moscow

References

  1. Symmes B.A., Stefanski A.L., Magin C.M., Evans C.M. Role of mucins in lung homeostasis: regulated expression and biosynthesis in health and disease. Biochem Soc Trans. 2018;46(3):707–19. doi: 10.1042/BST20170455.
  2. Ridley C., Thornton D.J. Mucins: the frontline defence of the lung. Biochem Soc Trans. 2018;46(5):1099–106. doi: 10.1042/BST20170402.
  3. Livraghi-Butrico A., Grubb B.R., Wilkinson K.J., et al. Contribution of mucus concentration and secreted mucins Muc5ac and Muc5b to the pathogenesis of muco-obstructive lung disease. Mucosal Immunol. 2017;10(3):829. doi: 10.1038/mi.2017.29.
  4. Song K.S., Lee W.J., Chung K.C., et al. Interleukin-1 beta and tumor necrosis factor-alpha induce MUC5AC overexpression through a mechanism involving ERK/p38 mitogen-activated protein kinases-MSK1-CREB activation in human airway epithelial cells. J Biol Chem. 2003;278(26):23243–50. doi: 10.1074/jbc.M300096200.
  5. Demouveaux B., Gouyer V., Gottrand F., et al. Gel-forming mucin interactome drives mucus viscoelasticity. Adv Colloid Interface Sci. 2018;252:69–82. doi: 10.1016/j.cis.2017.12.005.
  6. Mettelman R.C., Allen E.K., Thomas P.G. Mucosal immune responses to infection and vaccination in the respiratory tract. Immunity. 2022;55(5):749–80. doi: 10.1016/j.immuni.2022.04.013.
  7. Rogers D.F. Physiology of airway mucus secretion and pathophysiology of hypersecretion. Respir Care. 2007;52(9):1134–46; discussion 1146-9.
  8. Геппе Н.А., Малахов А.Б., Зайцева О.В. и др. Спорные и нерешенные вопросы в терапии кашля у детей в амбулаторной практике. Педиатрия. Consilium Medicum. 2017;4:40–5. [Geppe N.A., Malakhov A.B., Zaitseva O.V. Controversial and unresolved issues in the treatment of cough in children in outpatient practice. Pediatriya. Consilium Medicum. 2017;4:40–5. (In Russ.)].
  9. Геппе Н.А. и др. Острые инфекции дыхательных путей у детей. Диагностика, лечение, профилактика: клиническое руководство. 2-е изд. М., 2020. 254 с. [Geppe N.A. et al. Acute respiratory tract infections in children. Diagnosis, treatment, prevention: a clinical guide. 2nd ed. M., 2020. 254 p. (In Russ.)].
  10. Banerjee S., McCormack S. Acetylcysteine for Patients Requiring Secretion Clearance: A Review of Guidelines [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2019.
  11. Yang C., Montgomery M. Dornase alfa for cystic fibrosis. Cochrane Database Syst Rev. 2018 Sep 6;9(9):CD001127. doi: 10.1002/14651858.CD001127.pub4. Update in: Cochrane Database Syst Rev. 2021;3:CD001127. PMID: 30187450.
  12. Balsamo R., Lanata L., Egan C.G. Mucoactive drugs. Eur Respir Rev. 2010;19(116):127-33. doi: 10.1183/09059180.00003510.
  13. Albrecht H.H., Dicpinigaitis P.V., Guenin E.P. Role of guaifenesin in the management of chronic bronchitis and upper respiratory tract infections. Multidiscip Respir Med. 2017;12:31. doi: 10.1186/s40248-017-0113-4.
  14. Chen Y., Watson A.M., Williamson C.D., et al. Glucocorticoid receptor and HDAC2 mediate dexamethasone-induced repression of MUC5AC gene expression. Am J Respir. Cell Mol. Biol. 2012;47:637–44. doi: 10.1165/rcmb.2012-0009OC.
  15. Shinkai M., Foster G.H., Rubin B.K. Macrolide antibiotics modulate ERK phosphorylation and IL-8 and GM-CSF production by human bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2006;290(1):L75–85. doi: 10.1152/ajplung.00093.2005.
  16. Komiya K., Kawano S., Suzaki I., et al. Tiotropium inhibits mucin production stimulated by neutrophil elastase but not by IL-13. Pulm Pharmacol Ther. 2018;48:161–67. doi: 10.1016/j.pupt.2017.11.008.
  17. Tan Y.F., Zhang W., Yang L., Jiang S.P. The effect of formoterol on airway goblet cell hyperplasia and protein Muc5ac expression in asthmatic mice. Eur Rev Med Pharmacol Sci. 2011;15(7):743–50.
  18. European Medicine Agencies. Revised assessment report: Ambroxol and bromhexine containing medicinal products 2015. Available from: https://www.ema.europa.eu/en/documents/referral/ambroxol-bromhexine-article-31-referral-pracassessment-report_en.pdf
  19. Malerba M., Ragnoli B. Ambroxol in the 21st century: pharmacological and clinical update. Expert Opin Drug Metab Toxicol. 2008;4(8):1119–29. doi: 10.1517/17425255.4.8.1119.
  20. Scaglione F., Petrini O. Mucoactive Agents in the Therapy of Upper Respiratory Airways Infections: Fair to Describe Them Just as Mucoactive? Clin Med Insights Ear Nose Throat. 2019;12:1179550618821930. doi: 10.1177/1179550618821930.
  21. Germouty J., Jirou-Najou J.L. Clinical efficacy of ambroxol in the treatment of bronchial stasis. Clinical trial in 120 patients at two different doses. 4th Cong of the European Society of Pneumology (SEP) New Aspects in the treatment of Pulmonology and Upper Airways Diseases, Milan & Stresa 23–8. September 1985. Respiration. 1987;51(Suppl 1):37–41.
  22. Hsu L.S., Huang Y.F., Chiou Y.H., Nong B.R. An overview of mucoactive agents. Pediatr Respirol Crit Care Med [serial online]. 2020[cited 2023 Feb 21];4:54–7. Available from: https://www.prccm.org/text.asp?2020/4/4/54/320780
  23. Echaide M., Autilio C., Arroyo R., Perez-Gil J. Restoring pulmonary surfactant membranes and films at the respiratory surface. Biochim Biophys Acta Biomembr. 2017;1859(9 Pt B):1725–39. doi: 10.1016/j.bbamem.2017.03.015.
  24. Linssen R.S.N., Ma J., Bem R.A., Rubin B.K. Rational use of mucoactive medications to treat pediatric airway disease. Paediatr Respir Rev. 2020;36:8–14. doi: 10.1016/j.prrv.2020.06.007.
  25. Morgenroth K. J.B. Morphological features of the interaction between mucus and surfactant on the bronchial mucosa. Respiration 1985;47:225–31.
  26. Glowania A.M.R., Böhm M., Knopf A., Klimek L. The surfactant system – a new approach for treating the upper respiratory tract mucosa. Atemwegs Lungenkrankh 2011;37:S1–5.
  27. Fois G., Hobi N., Felder E., Ziegler A., et al. A new role for an old drug: Ambroxol triggers lysosomal exocytosis via pH-dependent Ca(2)(+) release from acidic Ca(2)(+) stores. Cell Calcium. 2015;58:628–37.
  28. Xiang J., Wang P. Efficacy of pulmonary surfactant combined with high-dose ambroxol hydrochloride in the treatment of neonatal respiratory distress syndrome. Exp Ther Med. 2019;18(1):654–58. doi: 10.3892/etm.2019.7615.
  29. Kumar P. Co-aerosolized Pulmonary Surfactant and Ambroxol for COVID-19 ARDS Intervention: What Are We Waiting for? Front Bioeng Biotechnol. 2020 Sep 25;8:577172. doi: 10.3389/fbioe.2020.577172.
  30. Seagrave J., Albrecht H.H., Hill D.B., et al. Effects of guaifenesin, N-acetylcysteine, and ambroxol on MUC5AC and mucociliary transport in primary differentiated human tracheal-bronchial cells. Respir Res. 2012;13(1):98. doi: 10.1186/1465-9921-13-98.
  31. Геппе Н.А., Шахназарова М.Д., Шаталина С.И. и др. Многообразие эффектов амброксола в терапии острых респираторных инфекций у детей. Фарматека. 2022.1.79–84. [Geppe N.A., Shakhnazarova M.D., Shatalina S.I., et al. The variety of effects of ambroxol in the treatment of acute respiratory infections in children. (In Russ.)].doi: 10.18565/pharmateca.2022.1.79-84.
  32. Stetinova V., Herout V., Kvetina J. In vitro and in vivo antioxidant activity of ambroxol. Clin Exp Med. 2004;4(3):152–58. doi: 10.1007/s10238-004-0050-3.
  33. Локшина Э.Э., Зайцева О.В. Особенности мукоактивной терапии в практике педиатра. Медицинский Совет. 2022;(1):97-104. [Lokshina E.E., Zaitseva O.V. Peculiarities of mucoactive therapy in pediatric practice. Meditsinskii Sovet. 2022;(1):97-104. (In Russ.)]. doi: 10.21518/2079-701X-2022-16-1-97-104.
  34. Takeda K., Miyahara N., Matsubara S., et al. Immunomodulatory effects of Ambroxol on airway Hyperresponsiveness and inflammation. Immune Netw. 2016;16:165–75. doi: 10.4110/In.2016.16.3.165.
  35. Zhu X., Wei Z., Liu X. Efficacy of Ambroxol Hydrochloride Combined with Amoxicillin Potassium Clavulanate Combination on Children with Bronchopneumonia and Its Impact on the Level of Inflammatory Factors. Evid Based Complement Alternat Med. 2022;2022:2604114. doi: 10.1155/2022/2604114.
  36. Cataldi M., Sblendorio V., Leo A., Piazza O. Biofilm-dependent airway infections: a role for ambroxol? Pulm Pharmacol The.r 2014;28:98–108.
  37. Zuqin Yang, et al. Effects and mechanisms of ambroxol inhalation (Mucosolvan®) in the treatment of neonatal pneumonia. Pharmazie 2017;72(10):604–07.
  38. Bradfute S.B., Ye C., E.C. Clarke, et al. Ambroxol and Ciprofloxacin Show Activity Against SARS-CoV2 in Vero E6 Cells at Clinically-Relevant Concentrations.bioRxiv 2020.08.11.245100. doi: 10.1101/2020.08.11.245100
  39. Carpinteiro A., Gripp B., Hoffmann M., et al. Inhibition of acid sphingomyelinase by ambroxol prevents SARS-CoV-2 entry into epithelial cells. J Biol Chem. 2021;296:100701. doi: 10.1016/j.jbc.2021.100701.
  40. Leffler A., Reckzeh J., Nau C. Block of sensory neuronal Na+ channels by the Secreolytic Ambroxol is associated with an interaction with local anesthetic binding sites. Eur J Pharmacol. 2010;630:19–28. doi: 10.1016/J.Ejphar.2009.12.027.
  41. Данные инструкций по медицинскому применению препаратов, содержащих амброксол. ГРЛС: [Электронный ресурс]. [These instructions for the medical use of drugs containing ambroxol. State Register of Medicines: (Electronic resource). (In Russ.)]. URL: https://grls.rosminzdrav.ru/grls.aspx (дата доступа / access date 08.10.2020).
  42. Геппе Н.А. Ингаляционная терапия заболеваний респираторной системыу детей Практическое руководство для врачей. M., 2022. 130 с. [Geppe N.A. Inhalation therapy of diseases of the respiratory system in children A practical guide for physicians. M., 2022. 130 p. (In Russ.)].
  43. Harriman A., et al. Can we mix nebuliser solution? Stability of drug admixtyres in solution for nebulization. Phatma.Pract.1996;6(9):347–48.
  44. Геппе Н.А., Батырева О.В., Малышев В.С. и др. Волнообразное течение бронхиальной астмы у детей. Терапия обострений. Трудный пациент. 2007;2(5):43–46. [Geppe N.A., Batyreva O.V., Malyshev V.S. Wave-like course of bronchial asthma in children. Exacerbation therapy. Trudnyi patsient.2007;2(5):43–46. (In Russ.)].
  45. Tewes F., Paluch K.J., Tajber L., et al. Steroid/mucokinetic hybrid nanoporous microparticles for pulmonary drug delivery. Eur J Pharm Biopharm. 2013;85(3):604–13.
  46. Комитет по оценке рисков фармаконадзора (PRAC) Пересмотренный отчет об оценке: лекарственные средства, содержащие амброксол и бромгексин. [Pharmacovigilance Risk Assessment Committee (PRAC) Revised evaluation report: medicinal products containing ambroxol and bromhexine. [(In Russ.)].URL: https://www.ema.europa.eu/en/medicines/human/referrals/ambroxol-bromhexine-containing- medicines
  47. Kantar A., Klimek L., Cazan D., et al. An overview of efficacy and safety of ambroxol for the treatment of acute and chronic respiratory diseases with a special regard to children. Multidiscip Respir Med. 2020;15(1):511. doi: 10.4081/mrm.2020.511.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1

Download (303KB)
Indexing metadata

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies