Cough in children: prevalence and significance in outpatient practice. Safety of the ambroxol molecule as a basis for choice of treatment

I.L. Vysochina, A.E. Abaturov


An analytical review was conducted in search engines PubMed, MedLine, Google Scholar, Web of Science, BioMed Central, The Cochrane Library, the specialized registry of the Cochrane group for acute respiratory infections, on the websites of relevant associations and respiratory societies of different countries on the problem of cough in outpatient practice; features of this phenomenon in children were reviewed. Assessment of the prevalence of cough according to literature search varies significantly depending on the questions used to evaluate it. Urgency of the cough problem is considered from the point of view of both the occurrence of this syndrome in the structure of patients’ visits and the need for medical consultations by primary care physicians, and the impaired quality of life of patients, families, its socio-economic significance. An analysis of the recommendations of the relevant associations and respiratory communities on the issue of cough and its management at the outpatient stage is carried out. It is shown that the existing recommendations in pediatrics differ from those for adult patients. A review of the literature available in search engines showed that the use of algorithms and standards for managing patients with cough leads to earlier diagnosis and improved clinical results, such as reducing the duration of cough and improving the quality of life of patients, including children. A discussion was held of the dilemma of treating or not treating cough from the point of view of not only evidence-based medicine, but also taking into account parents’ surveys of how prepared the patients are, relatively speaking, to do almost nothing when cough develops in children. The evidence base on the efficacy and safety of administering ambroxol as the most commonly used drug from the over-the-counter group in children with respiratory tract infections, and the results of studies confirming the possibility of its use in cough in pediatric practice are presented.


cough; children; treatment; ambroxol


Gucci M, Tarò D, Memmini C. A controlled study on the action of a new formulation of ambroxol in asth-matiform bronchitis in children. Minerva Pediatr. 1989 Feb;41(2):91-5.

Beeh KM, Beier J, Esperester A, Paul LD. Antiinflammatory properties of ambroxol. Eur J Med Res. 2008 Dec 3;13(12):557-62.

Berni M, Collina A, Zavattini G. Ambroxol in bronchopulmonary pathology in children. Clin Ter. 1983 Sep 15;106(5):351-5.

Bianchi, M. Ambroxol inhibits interleukin 1 and tumor necrosis factor production in human mononuclear cells. Agents Actions. 1990 Nov;31(3-4):275-9. doi: 10.1007/bf01997619.

Balsamo R, Lanata L, Egan CG. Mucoactive drugs. Eur Respir Rev. 2010 Jun;19(116):127-33. doi: 10.1183/09059180.00003510.

Britt H, Miller GC, Charles J, et al. General practice activity in Australia 2009-10. Australian Institute of Health and Welfare; 2010. 216 p.

Brooke AM, Lambert PC, Burton PR, Clarke C, Luyt DK, Simpson H. Recurrent cough: natural history and significance in infancy and early childhood. Pediatr Pulmonol. 1998 Oct;26(4):256-61. doi: 10.1002/(sici)1099-0496(199810)26:4<256::aid-ppul4>;2-o.

Burr ML, Anderson HR, Austin JB, et al. Respiratory symptoms and home environment in children: a national survey. Thorax. 1999 Jan;54(1):27-32. doi: 10.1136/thx.54.1.27.

Bush A. Paediatric problems of cough. Pulm Pharmacol Ther. 2002;15(3):309-15. DOI: 10.1006/pupt.2002.0340.

Cazan D, Klimek L, Sperl A, Plomer M, Kölsch S. Safety of ambroxol in the treatment of airway diseases in adult patients. Expert Opin Drug Saf. 2018 Dec;17(12):1211-1224. doi: 10.1080/14740338.2018.1533954.

Cegla UH. Long-term therapy over 2 years with Ambroxol (Mucosolvan) retard capsules in patients with chronic bronchitis. Prax Klin Pneumol. 1988 Sep;42(9):715-21.

Chang AB, Oppenheimer JJ, Weinberger M, Grant CC, Rubin BK, Irwin RS; CHEST Expert Cough Panel. Etiologies of Chronic Cough in Pediatric Cohorts: CHEST Guideline and Expert Panel Report. Chest. 2017 Sep;152(3):607-617. doi: 10.1016/j.chest.2017.06.006.

Chang AB, Oppenheimer JJ, Weinberger M, Weir K, Rubin BK, Irwin RS. Use of management pathways or algorithms in children with chronic cough: systematic reviews. Chest. 2016 Jan;149(1):106-19. doi: 10.1378/chest.15-1403.

Chang AB, Robertson CF, Van Asperen PP, et al. A multicenter study on chronic cough in children: burden and etiologies based on a standardized management pathway. Chest. 2012 Oct;142(4):943-950. doi: 10.1378/chest.11-2725.

Chang AB, Landau LI, Van Asperen PP, et al. Cough in children: definitions and clinical evaluation. Med J Aust. 2006 Apr 17;184(8):398-403.

Chang AB. Cough: are children really different to adults? Cough. 2005 Sep 20;1:7.

Cornford CS, Morgan M, Ridsdale L. Why do mothers consult when their children cough? Fam Pract. 1993 Jun;10(2):193-6. doi: 10.1093/fampra/10.2.193.

Paleari D, Rossi GA, Nicolini G, Olivieri D. Ambroxol: a multifaceted molecule with additional therapeutic potentials in respiratory disorders of childhood. Expert Opin Drug Discov. 2011 Nov;6(11):1203-14. doi: 10.1517/17460441.2011.629646.

de Mey C, Peil H, Kölsch S, Bubeck J, Vix JM. Efficacy and safety of Ambroxol lozenges in the treatment of acute uncomplicated sore throat. Arzneimittelforschung. 2008;58(11):557-68. doi: 10.1055/s-0031-1296557.

Disse BG, Ziegler HW. Pharmacodynamic mechanism and therapeutic activity of Ambroxol in animal experiments. Respiration. 1987;51 Suppl 1:15-22. doi: 10.1159/000195270.

Disse K. The pharmacology of ambroxol – review and new results. Eur J Respir Dis Suppl. 1987;153:255-62.

European Medicines Agency. Revised assessment report—procedure under article 31 of directive 2001/83/EC resulting from pharmacovigilance data: Ambroxol and bromhexine containing medicinal products. Available from: Accessed Sep 10, 2015.

Fois G, Hobi N, Felder E, et al. A new role for an old drug: Ambroxol triggers lysosomal exocytosis via Ph-dependent Ca2+ release from acidic Ca2+ stores. Cell Calcium. 2015 Dec;58(6):628-37. doi: 10.1016/j.ceca.2015.10.002.

Gené R, Poderoso JJ, Corazza C, et al. Influence of ambroxol on amoxicillin levels in bronchoalveolar lavage fluid. Arzneimittelforschung. 1987 Aug;37(8):967-8.

Guyatt GH, Townsend M, Kazim F, Newhouse MT. A controlled trial of ambroxol in chronic bronchitis. Chest. 1987 Oct;92(4):618-20. doi: 10.1378/chest.92.4.618.

Hay AD, Heron J, Ness A; ALSPAC study team. The prevalence of symptoms and consultations in preschool children in the Avon Longitudinal study of Parents and Children (ALSPAC): a prospective cohort study. Fam Pract. 2005 Aug;22(4):367-74. doi: 10.1093/fampra/cmi035.

Hay AD, Wilson A, Fahey T, Peters TJ. The duration of acute cough in pre-school children presenting to primary care: a prospective cohort study. Fam Pract. 2003 Dec;20(6):696-705. doi: 10.1093/fampra/cmg613.

Hay AD, Wilson AD. The natural history of acute cough in children aged 0–4 years in primary care: a systematic review. Br J Gen Pract. 2002 May;52(478):401-9.

Irwin RS, Gutterman DD.  American College of Chest Physicians’ cough guidelines. Lancet. 2006 Mar 25;367(9515):981. doi: 10.1016/S0140-6736(06)68414-6.

Kai J. What worries parents when their preschool children are acutely ill, and why: a qualitative study. BMJ. 1996 Oct 19;313(7063):983-6. doi: 10.1136/bmj.313.7063.983.

Kamei J, Nakanishi Y, Ishikawa Y, Hayashi SS, Asato M, Ohsawa M. Possible involvement of tetrodotoxin-resistant sodium channels in cough reflex. Eur J Pharmacol. 2011 Feb 10;652(1-3):117-20. doi: 10.1016/j.ejphar.2010.11.019.

Karabel M, Kelekçi S, Karabel D, Gürkan MF. The evaluation of children with prolonged cough accompanied by American College of Chest Physicians guidelines. Clin Respir J. 2014 Apr;8(2):152-9. doi: 10.1111/crj.12052.

Kardos P, Beeh KM, Sent U, Mueck T, Gräter H, Michel MC. Characterization of differential patient profiles and therapeutic responses of pharmacy customers for four ambroxol formulations. BMC Pharmacol Toxicol. 2018 Jul 4;19(1):40. doi: 10.1186/s40360-018-0229-y.

Kimya Y, Küçükkömürcü S, Ozan H, Uncu G. Antenatal ambroxol usage in the prevention of infant respiratory distress syndrome. Beneficial and adverse effects. Clin Exp Obstet Gynecol. 1995;22(3):204-11.

Leder K, Sinclair MI, Mitakakis TZ, Hellard ME, Forbes A. A community based study of respiratory episodes in Melbourne, Australia. Aust N Z J Public Health. 2003;27(4):399-404. doi: 10.1111/j.1467-842x.2003.tb00416.x.

Lee CS, Jang YY, Song JS, Song JH, Han ES. Ambroxol inhibits peroxynitrite-induced damage of alpha1-antiproteinase and free radical production in activated phagocytic cells. Pharmacol Toxicol. 2002 Sep;91(3):140-9. doi: 10.1034/j.1600-0773.2002.910309.x.

Malerba M, Ragnoli B. Ambroxol in the 21st century: pharmacological and clinical update. Expert Opin Drug Metab Toxicol. 2008 Aug;4(8):1119-29. doi: 10.1517/17425255.4.8.1119.

Marchant JM, Newcombe PA, Juniper EF, Sheffield JK, Stathis SL, Chang AB. What is the burden of chronic cough for families? Chest. 2008 Aug;134(2):303-309. doi: 10.1378/chest.07-2236.

Marchant JM, Masters IB, Taylor SM, Cox NC, Seymour GJ, Chang AB. Evaluation and outcome of young children with chronic cough. Chest. 2006 May;129(5):1132-41. DOI: 10.1378/chest.129.5.1132.

Matthys H, de Mey C, Carls C, Ryś A, Geib A, Wittig T. Efficacy and tolerability of myrtol standardized in acute bronchitis. A multi-centre, randomised, double-blind, placebo-controlled parallel group clinical trial vs. cefuroxime and ambroxol. Arzneimittelforschung. 2000 Aug;50(8):700-11. doi: 10.1055/s-0031-1300276.

McCallum GB, Bailey EJ, Morris PS, Chang AB. Clinical pathways for chronic cough in children. Cochrane Database Syst Rev. 2014 Sep 22;(9):CD006595. doi: 10.1002/14651858.CD006595.pub3.

Monto AS. Studies of the community and family: acute respiratory illness and infection. Epidemiol Rev. 1994;16(2):351-73. doi: 10.1093/oxfordjournals.epirev.a036158.

Morice A, Kardos P. Comprehensive evidence-based review on European antitussives. BMJ Open Respir Res. 2016 Aug 5;3(1):e000137. doi: 10.1136/bmjresp-2016-000137.

Munyard P, Bush A. How much coughing is normal? Arch Dis Child. 1996 Jun;74(6):531-4. doi: 10.1136/adc.74.6.531.

Ninan TK, Macdonald L, Russell G. Persistent nocturnal cough in childhood: a population based study. Arch Dis Child. 1995 Nov;73(5):403-7. doi: 10.1136/adc.73.5.403.

Nobata K, Fujimura M, Ishiura Y, Myou S, Nakao S. Ambroxol for the prevention of acute upper respiratory disease. Clin Exp Med. 2006 Jun;6(2):79-83. doi: 10.1007/s10238-006-0099-2.

Olivieri D, Zavattini G, Tomasini G, et al. Ambroxol for the prevention of chronic bronchitis exacerbations: long-term multicenter trial. Respiration. 1987;51 Suppl 1:42-51. doi: 10.1159/000195274. 

Paganin F, Bouvet O, Chanez P, et al. Evaluation of the effects of ambroxol on the ofloxacin concentrations in bronchial tissues in COPD patients with infectious exacerbation. Biopharm Drug Dispos. 1995 Jul;16(5):393-401. doi: 10.1002/bdd.2510160504.

Paleari D, Rossi GA, Nicolini G, Olivieri D. Ambroxol: a multifaceted molecule with additional therapeutic potentials in respiratory disorders of childhood. Expert Opin Drug Discov. 2011 Nov;6(11):1203-14. doi: 10.1517/17460441.2011.629646.

Jurca M, Ramette A, Dogaru CM, et al.  Prevalence of cough throughout childhood: A cohort study. PLoS One. 2017 May 24;12(5):e0177485. doi: 10.1371/journal.pone.0177485.

Shields MD, Bush A, Everard ML, McKenzie S, Primhak R; British Thoracic Society Cough Guideline Group. Recommendations for the assessment and management of cough in children. Thorax. 2008 Apr;63 Suppl 3:iii1-iii15. doi: 10.1136/thx.2007.077370.

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 Jan 9;12:1179550618821930. doi: 10.1177/1179550618821930.

Shann F. How often do children cough? Lancet. 1996 Sep 14;348(9029):699-700. doi: 10.1016/S0140-6736(05)65602-4.

Spátola J, Poderoso JJ, Wiemeyer JC, Fernández M, Guerreiro RB, Corazza C. Influence of ambroxol on lung tissue penetration of amoxicillin. Arzneimittelforschung. 1987 Aug;37(8):965-6.

Su X, Wang L, Song Y, Bai C. Ambroxol inhibited proinflammatory cytokines, reduced lung inflammation and accelerated recovery from LPS-induced ALI. Intensive Care Med. 2004 Jan;30(1):133-40. doi: 10.1007/s00134-003-2001-y.

Takeda K, Miyahara N, Matsubara S, et al. Immunomodulatory effects of Ambroxol on airway Hyperresponsiveness and inflammation. Immune Netw. 2016 Jun;16(3):165-75. doi: 10.4110/in.2016.16.3.165.

Thompson M, Vodicka TA, Blair PS, Buckley DI, Heneghan C, Hay AD. Duration of symptoms of respiratory tract infections in children: systematic review. BMJ. 2013 Dec 11;347:f7027. doi: 10.1136/bmj.f7027.

Thomson F, Masters IB, Chang AB. Persistent cough in children and the overuse of medications. J Paediatr Child Health. 2002 Dec;38(6):578-81. doi: 10.1046/j.1440-1754.2002.00045.x.

Wauer RR, Schmalisch G, Böhme B, Arand J, Lehmann D. Randomised double blind trial of ambroxol for the treatment of respiratory distress syndrome. Eur J Pediatr. 1992 May;151(5):357-63. doi: 10.1007/bf02113258.

Weinmann HM. Ambroxol in paediatrics. Therapiewoche. 1981;31:7940-7947.

Whitburn S, Costelloe C, Montgomery AA. The frequency distribution of presenting symptoms in children aged six months to six years to primary care. Prim Health Care Res Dev. 2011 Apr;12(2):123-34. doi: 10.1017/S146342361000040X.

Wiemeyer JC. Influence of ambroxol on broncho-pulmonary levels of antibiotics. Arzneimittelforschung. 1981;31(6):974-6.

Yamaya M, Nishimura H, Nadine LK, Ota C, Kubo H, Nagatomi R. Ambroxol inhibits rhinovirus infection in primary cultures of human tracheal epithelial cells. Arch Pharm Res. 2014 Apr;37(4):520-9. doi: 10.1007/s12272-013-0210-7.

Abaturov AY. Mucolytic therapy for inflammatory diseases of the tracheobronchial system in children. Medicus Amicus. 2006;1. Available from: (in Russian).

Andrukh VS. Cough in children: gp’s algorithm of actions. Family medicine. 2017:(69):125-126. doi: 10.30841/2307-5112.1(69).2017.103266. (in Ukrainian).

Besh LV. Cough among children: diagnostic approaches and treatment tactics. Sovremennaya pediatriya. 2015;(65):67-71. doi: 10.15574/SP.2015.65.67. (in Ukrainian).

Vysochyna IL, Chernyshоva OY. Cough in children: mechanisms and approaches to treatment. Zdorovye rebyonka. 2013;(8):101-105. (in Russian).

Vysochyna IL, Petrenko LL, Dityatkovsky VA. Cough: Differential Approaches to Treatment. Zdorov`e rebenka. 2014;(52):117-120. (in Russian).

Glyadyelova, NV. Mucolytic druds for child cough controlling. Sovremennaya pediatriya. 2014;(59):70-75. (in Russian).

Zaitsev AA. Mucoactive cough therapy: what is behind the horizon? Lechashchiy vrach. 2018;(10):22-27. ([in Russian).

Krivopustov SP. Modern approaches to the diagnosis and treatment of cough in children. Mystetstvo likuvannya. 2003;3. Available from: (in Ukrainian).

Maydannik VG. Cough in children: causes, mechanisms, diagnosis and treatment. Sovremennaya pediatriya. 2005;(8):111-117. (in Russian).

Marushko YV. Mucoactive therapy in cough syndrome in children. Ukrainian Medical Journal. 2015;(105). (in Ukrainian).

Mizernitskiy YL, Melnikova IM. Differentiation mucolytic therapy for acute and chronic bronchopulmonary diseases in pediatric practice 2016. Rossiyskiy vestnik perinatologii i pediatrii . 2016;(4):23-30. doi: 10.21508/1027-4065-2016-61-4-23-30. (in Russian).

Rechkina OO. Cough in Children: Current Approaches to the Treatment. Zdorov`e rebenka. 2016;(70):67-71. doi: 10.22141/2224-0551.2.70.2016.73812. (in Russian).

Ministry of Health of Ukraine. Order 327 dated June 8 2015: On approval and implementation of medical and technological documents on standardization of cough care. Available from:

Copyright (c) 2020 CHILD`S HEALTH

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.


© Publishing House Zaslavsky, 1997-2020


   Seo анализ сайта