Local therapy for the treatment of paediatric respiratory diseases

The problem of determining the tactics of prescribing topical therapy in respiratory pathology remains relevant in pediatric practice. Local therapy is one of the components of complex treatment of respiratory diseases of upper respiratory tract, ENT organs, however, in the presence of appropriate indications according to the current federal recommendations for the appointment of antibacterial drugs of systemic action can not replace them. The article presents a modern review of scientific literature data on the role of topical drugs in respiratory diseases. Numerous clinical and experimental studies confirm the effectiveness of topical preparation benzydamine, which has a unique combined action, simultaneously influencing various pathogenetic links of inflammation. Benzydamine exhibits antiseptic and anti-inflammatory properties, effectively inhibiting the growth of both Gram-positive and Gram-negative bacteria, as well as some types of fungi, demonstrating resistance to the mechanisms of antibacterial resistance. The key advantage of benzydamine is its ability to penetrate into the focus of inflammation, reaching the necessary therapeutic concentrations. The mechanism of this action is associated with modulation of the activity of various inflammatory mediators such as cytokines and prostaglandins, resulting in a reduction of the inflammatory response. Moreover, benzydamine has immunomodulatory properties, stimulating local immunity and enhancing the activity of local immune cells. This contributes to faster and more effective elimination of the infectious agent and accelerated repair of damaged tissues. Prospective results and detailed evaluation of clinical efficacy of benzydamine, which has a complex of anti-inflammatory properties, were the basis for recommending it as a safe and effective topical drug in the treatment of infectious and inflammatory diseases of the respiratory tract, ENT organs, oral cavity.

1. Геппе НА (ред.). Острые инфекции дыхательных путей у детей. Диагностика, лечение, профилактика. 3-е изд. М.: МедКом-Про; 2023. 348 с.

2. Чучалин АГ (ред.). Респираторная медицина. 3-е изд. М: ПульмоМедиа; 2024. Т. 1. 668 с. https://doi.org/10.18093/987-5-6048754-9-0.

3. Мизерницкий ЮЛ, Мельникова ИМ. Кашель и его терапия у детей. М.: Медпрактика-М; 2020. 244 с.

4. Pavlenko VA, Melnikova IM, Mizernitsky YL. Clinical and diagnostic aspects of prediction of bronchial asthma in early childhood. Meditsinskiy Sovet. 2017;(9):70–75. (In Russ.) https://doi.org/10.21518/2079-701X-2017-9-70-75.

5. Davydova AN. Efficiency of benzydamine use in treatment of URTI (including COVID-19) in child patients. Vestnik Oto-Rino-Laringologii. 2022;87(5):99–103. (In Russ.) https://doi.org/10.17116/otorino20228705199.

6. Gambadauro A, Galletta F, Pomi AL, Manti S, Piedimonte G. Immune Response to Respiratory Viral Infections. Int J Mol Sci. 2024;25(11):6178. https://doi.org/10.3390/ijms25116178.

7. Melnikova IM, Dorovskaya NL, Mizernitskii YuL, Nekrasova MV, Tikhomirova MA. Present course of community-acquired pneumonia in children. International Research Journal. 2024;(9). (In Russ.) https://doi.org/10.60797/IRJ.2024.147.25.

8. Ryazantsev SV, Artyushkin SA, Eremin SA, Artyushkina VK, Eremina NV. Topical therapy algorithm in the treatment of tonsillopharyngitis. Rossiiskaya Otorinolaringologiya. 2023;22(4):133–139. (In Russ.) https://doi.org/10.18692/1810-4800-2023-4-133-139.

9. Mel’nikova IM, Udal’tsova EV, Mizernitsky YL. Cough in children: when and how to treat? Meditsinskiy Sovet. 2017;(1):116–120. (In Russ.) https://doi.org/10.21518/2079-701X-2017-1-116-120.

10. Melekhina EV, Preobrazhenskaia DV, Muzyka AD, Soldatova EYu, Gorelov AV. Recurrent respiratory infections and active herpesvirus infections in children: problems and solutions. RMJ. Medical Review. 2023;7(11):704–712. (In Russ.) https://doi.org/10.32364/2587-6821-2023-7-11-2.

11. Chernyshova OE. A rational approach to the treatment of acute tonsillopharyngitis in children. Child’s Health. 2016;(7):72–79. (In Russ.) https://doi.org/10.22141/2224-0551.7.75.2016.86728.

12. Savenkova MS, Isaeva EI, Vetrova EN, Kraseva GN, Abramova NA, Shabat MB et al. Role of antiviral therapy in respiratory infections in children: analysis of clinical and laboratory observations. Clinical Practice in Pediatrics. 2022;17(6):45–54. (In Russ.) https://doi.org/10.20953/18177646-2022-6-45-54.

13. Gergiev VF, Svistushkin VM, Nikiforova GN, Timurzieva AB. Acute infectious inflammatory throat diseases: some aspects of diagnostics and the possibility of medicamental correction. Meditsinskiy Sovet. 2018;(8):20–22. (In Russ.) https://doi.org/10.21518/2079-701X-2018-8-20-22.

14. Krivopalov AA, Shatalov VA, Shervashidze SV. New prospects for local etiotropic treatment of acute respiratory viral infections. Meditsinskiy Sovet. 2019;(8):105–108. (In Russ.) https://doi.org/10.21518/2079-701X-2019-8-105-108.

15. Slavsky AN, Meitel IY. Sore throat: justification of the optimal drug selection. Meditsinskiy Sovet. 2016;(18):128–132. (In Russ.) https://doi.org/10.21518/2079-701X-2016-18-128-132.

16. Daifalla N, Cayabyab MJ, Xie E, Kim HB, Tzipori S, Stashenko P et al. Commensal Streptococcus mitis is a unique vector for oral mucosal vaccination. Microbes Infect. 2015;17(3):237–242. https://doi.org/10.1016/j.micinf.2014.11.002.

17. Ruzhentsova TA, Garbuzov AA, Bitsueva AB, Rubleva OV, Gorbunov SG, Meshkova NA et al. Optimal topical drug for COVID-19 therapy in children. Infectious Diseases. 2022;20(2):41–46. (In Russ.) Available at: https://www.phdynasty.ru/katalog/zhurnaly/infektsionnye-bolezni/2022/tom-20-nomer-2/44330.

18. Kirilyuk AA. Clinical pharmacology features of the drugs to treat throat and oral cavity diseases. Vestnik Farmatsii. 2023;(1):48–70. (In Russ.) Available at: https://vestnik-pharm.vsmu.by/rezyume/2023-1-48-70.

19. Kolosova NG, Shatalina SI. Correct algorithm of ARVI treatment in pediatric patients. Meditsinskiy Sovet. 2017;(19):158–161. (In Russ.) https://doi.org/10.21518/2079-701X-2017-19-158-161.

20. Acar YA, Kalkan M, Çetin R, Çevik E, Çınar O. Acute Psychotic Symptoms Due to Benzydamine Hydrochloride Abuse with Alcohol. Case Rep Psychiatry. 2014;2014:290365. https://doi.org/10.1155/2014/290365.

21. Ősz BE, Jîtcă G, Sălcudean A, Rusz CM, Vari CE. Benzydamine – An Affordable Over-the-Counter Drug with Psychoactive Properties – From Chemical Structure to Possible Pharmacological Properties. Pharmaceuticals. 2023;16(4):566. https://doi.org/10.3390/ph16040566.

22. Gürü M, Şafak Y, Cengiz GF, Kuru E, Örsel S. Chronic psychosis related to benzydamine hydrochloride abuse. Neurocase. 2019;25(3-4):156–158. https://doi.org/10.1080/13554794.2019.1617318.

23. Schachtel BP, Padjarino DA. Randomized, double-blind, placebo-controlled model demonstrating a local effect of benzydamine in children with tonsillopharyngitis. Child’s Health. 2012;(8):73–76. (In Russ.) Available at: https://www.elibrary.ru/phtodg.

24. Quane PA, Graham GG, Ziegler JB. Pharmacology of benzydamine. Inflammopharmacology. 1998;6(2):95–107. https://doi.org/10.1007/s10787-998-0026-0.

25. Engen SA, Rukke HV, Becattini S, Jarrossay D, Blix IJ, Petersen FC et al. The oral commensal Streptococcus mitis shows a mixed memory Th cell signature that is similar to and cross-reactive with Streptococcus pneumoniae. PLoS ONE. 2014;9(8):e104306. https://doi.org/10.1371/journal.pone.0104306.

26. Bossi P, Gurizzan C, Guntinas-Lichius O, Hainarosie R, Lancini D. The present and the future of benzydamine: expert opinion paper. Front Oral Health. 2023;4:1191319. https://doi.org/10.3389/froh.2023.1191319.

27. Fanaki NH, el-Nakeeb MA. Antimicrobial activity of benzydamine, a nonsteroid anti-inflammatory agent. J Chemother. 1992;4(6):347–352. https://doi.org/10.1080/1120009X.1992.11739190.

28. Iwase T, Uehara Y, Shinji H, Tajima A, Seo H, Takada K et al. Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization. Nature. 2010;465(7296):346–349. https://doi.org/10.1038/nature09074.

29. Chen HW, Liu PF, Liu YT, Kuo S, Zhang XQ, Schooley RT et al. Nasal commensal Staphylococcus epidermidis counteracts influenza virus. Sci. Rep. 2016;6:27870. https://doi.org/10.1038/srep27870.

30. Mathivanan S, Torre-Martinez R, Wolf C, Mangano G, Polenzani L, Milanese C, Ferrer-Montiel A. Effect of econazole and benzydamine on sensory neurons in culture. J Physiol Pharmacol. 2016;67(6):851–858. Available at: https://www.jpp.krakow.pl/journal/archive/12_16/articles/06_article.html.

31. Ferrer-Montiel AV, Nikolaeva-Koleva M, Vergassola M, Mangano G, Polenzani L, Espinosa A et al. Benzydamine inhibits neuronal excitability induced by inflammatory mediators to relieve pain. Biophys J. 2022;121(3):504А–505А. https://doi.org/10.1016/j.bpj.2021.11.262.

32. Nikolaeva-Koleva M, Espinosa A, Vergassola M, Polenzani L, Mangano G, Ragni L et al. Benzydamine plays a role in limiting inflammatory pain induced by neuronal sensitization. Mol Pain. 2023;19:17448069231204191. https://doi.org/10.1177/17448069231204191.

33. Krivopalov AA, Ryazantsev SV, Eremin SA, Shamkina PA. Clinical efficacy of benzydamine drugs in the treatment of exacerbations of chronic tonsillopharyngitis. RMJ. Medical Review. 2019;3(2-2):36–41. (In Russ.) Available at: https://www.rmj.ru/articles/otorinolaringologiya/Klinicheskaya_effektivnosty_preparatov_benzidamina_v_terapii_obostreniy_hronicheskogo_tonzillofaringita/.

34. Poryadin GW, Salmasi JM, Kazimirsky AN. The mechanism of action of benzydamine on local infectious inflammation. Farmateka. 2018;(13):76–83. https://doi.org/10.18565/pharmateca.2018.13.76-83.

35. Slukin PV, Fursova NK, Briko NI. Antibacterial Activity of Benzydamine Hydrochloride against Clinical Isolates of Bacteria, isolated from people in Russia and Spain. Epidemiologiya i Vaktsinoprofilaktika. 2018;17(6):11–18. (In Russ.) https://doi.org/10.31631/2073-3046-2018-17-11-18.

36. Detusheva EV, Fursova NK, Kukes IV. Evaluation of the antibacterial activity of the preparation benzydamine hydrochloride. Meditsinskiy Sovet. 2022;16(8): 49–55. (In Russ.) https://doi.org/10.21518/2079-701X-2022-16-8-49-55.

37. Slukin PV, Fursova NK, Kukes IV, Briko NI. Evaluation of the ability of benzydamine hydrochloride to inhibit planktonic cells, as well as growing and mature biofilms of clinically important microorganisms. Farmateka. 2021;28(1): 102–107. (In Russ.) https://doi.org/10.18565/pharmateca.2021.1.102-107.

38. Ruzhentsova TA, Garbuzov AA, Meshkova NA, Popova RV, Slyusar OI, Zatevalov AM The effect of topical drugs on the course of ARVI in children in modern conditions. Immunopathology, Allergology, Infectology. 2024;(1):86–92. (In Russ.) https://doi.org/10.14427/jipai.2024.1.86.

39. Ruzhentsova TA, Babachenko IV, Odinaeva ND, Panova LD, Gurov AV, Soboleva NG et al. Resolution of the Council of Experts. Current challenges and treatment options for upper respiratory tract infections in children. Infectious Diseases. 2023;21(3):127–136. (In Russ.) https://doi.org/10.20953/1729-9225-2023-3-127-136.

40. Khan A, Bibi S, Kanwal H, Kalsoom UE, Hussain H. Omicron: A new face of COVID-19 pandemic. Health Sci Rep. 2022;5(2):e526. https://doi.org/10.1002/hsr2.526.

41. Yasuhara J, Kuno T, Takagi H, Sumitomo N. Clinical characteristics of COVID-19 in children: A systematic review. Pediatr Pulmonol. 2020;55(10):2565–2575. https://doi.org/10.1002/ppul.24991.

42. Valerio C, Di Loreto G, Salvatori E, Cattaneo A. Comparative evaluation of rapidity of action of benzydamine hydrochloride 0.3% oromucosal spray and benzydamine hydrochloride 3 mg lozenges in patients with acute sore throat: a phase IV randomized trial. Medicine. 2023;102(13):e33367. https://doi.org/10.1097/MD.0000000000033367.

43. Kuriyama A, Aga M, Maeda H. Topical benzydamine hydrochloride for prevention of postoperative sore throat in adults undergoing tracheal intubation for elective surgery: a systematic review and meta-analysis. Anaesthesia. 2018;73(7):889–900. https://doi.org/10.1111/anae.14224.

44. Nicolatou-Galitis O, Bossi P, Orlandi E, Bensadoun RJ. The role of benzydamine in prevention and treatment of chemoradiotherapy-induced mucositis. Support Care Cancer. 2021;29(10):5701–5709. https://doi.org/10.1007/s00520-021-06048-5.

45. Elsaadany B, Anayb SM, Mashhour K, Yossif M, Zahran F. Rebamipide gargle and benzydamine gargle in prevention and management of chemo-radiotherapy and radiotherapy-induced oral mucositis in head and neck cancer patients (randomized clinical trial). BMC Oral Health. 2024;24(1):645. https://doi.org/10.1186/s12903-024-04379-3.

46. Passali D, Barat V, Cadevall O, Freire HM, Grattagliano I, Gutu I et al. International Delphi-based consensus on the appropriate use and effect of Benzydamine hydrochloride in the treatment of sore throat. BMC Prim Care. 2022;23(1):296. https://doi.org/10.1186/s12875-022-01901-w.

47. Passali D, Arezzo MF, Rose AD, Simone GD, Forte G, Jablko-Musial M, Mösges R. Benzydamine hydrochloride for the treatment of sore throat and irritative/inflammatory conditions of the oropharynx: a cross-national survey among pharmacists and general practitioners. BMC Prim Care. 2022;23(1):154. https://doi.org/10.1186/s12875-022-01762-3.