Terapevticheskii arkhivTerapevticheskii arkhivТерапевтический архив0040-36602309-5342LLC Obyedinennaya Redaktsiya7127410.26442/00403660.2021.04.200814ReviewsОбзорыReview ArticleExtraesophageal signs of gastroesophageal reflux disease: otorhinolaryngologist’s viewВнепищеводные проявления гастроэзофагеальной рефлюксной болезни: взгляд оториноларингологаhttps://orcid.org/0000-0003-4613-922XRadtsigElena Yu.РадцигЕлена Юрьевна
Russian Federation

д.м.н., проф., проф. каф. оториноларингологии педиатрического фак-та

Radtsig_e@rsmu.ruhttps://orcid.org/0000-0001-7514-4090KonstantinovDaniil I.КонстантиновДаниил Игоревич
Russian Federation

клинический ординатор каф. оториноларингологии педиатрического фак-та

Radtsig_e@rsmu.ruPirogov Russian National Research Medical UniversityФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России150420219345215250306202103062021Copyright ©; 2021, Consilium MedicumCopyright ©; 2021, ООО "Консилиум Медикум"2021Consilium MedicumООО "Консилиум Медикум"https://creativecommons.org/licenses/by-nc-sa/4.0https://ter-arkhiv.ru/0040-3660/article/view/71274

The data on association between various pathologies of the ENT organs and gastroesophageal reflux disease (GERD) is analysed in the article. The variety of extraesophageal signs of GERD in children and adults is given, what is advisable to inform physicians of different specialties about the possibilities of antireflux therapy. These options are expanded with the emergence of a unique new drug, Alfasoxx. Its bioadhesive formula is based on hyaluronic acid and chondroitin sulphate thereby protecting the esophageal mucosa. Alfasoxx acts on the surface of the esophageal mucosa without penetrating into the systemic bloodstream and it also has a low allergenic potential, which has been confirmed by numerous studies. With its healing and repairing effect on erosive lesions of the esophageal epithelium, Alfasoxx in combination with proton pump inhibitors is more effective in achieving regression of clinical manifestations of the disease and improving patients’ quality of life (according to SF-36 questionnaire) compared to proton pump inhibitors monotherapy.

В статье проведен анализ данных о связи различной патологии ЛОР-органов и гастроэзофагеальной рефлюксной болезни (ГЭРБ). Учитывая многообразие экстраэзофагеальных признаков ГЭРБ у детей и взрослых, целесообразно информирование врачей разных специальностей о возможностях антирефлюксной терапии. Эти возможности расширяются с появлением нового уникального препарата Альфазокс – биоадгезивной формулы на основе гиалуроновой кислоты и хондроитина сульфата для защиты слизистой оболочки пищевода. Альфазокс действует на поверхности слизистой пищевода, не проникая в системный кровоток, обладает низким аллергенным потенциалом, что подтверждено многочисленными исследованиями. Оказывающий заживляющее и восстанавливающее действие при эрозивных повреждениях эпителия пищевода Альфазокс в комбинации с ингибиторами протонной помпы позволяет более эффективно добиться регрессии клинических проявлений заболевания и улучшения качества жизни пациентов (согласно опроснику SF-36) по сравнению с монотерапией ингибиторами протонной помпы.

gastroesophageal reflux disease (GERD)extraesophageal signs of GERDENT-pathology and GERDantireflux-therapyAlfasoxxгастроэзофагеальная рефлюксная болезнь (ГЭРБ)экстраэзофагеальные признаки ГЭРБЛОР-патология и ГЭРБантирефлюксная терапияАльфазоксMosca F, Rossillo V, Leone CA. Manifestations of gastro-pharyngo-laryngeal reflux disease. Acta Otorhinolaryngol Ital. 2006;26(5):247-51Федеральные клинические рекомендации по диагностике и лечению гастроэзофагеальной рефлюксной болезни у детей. Союз педиатров России. 2015 г. [Federal clinical guidelines for the diagnosis and treatment of gastroesophageal reflux disease in children. Union of Pediatricians of Russia. 2015 (In Russ.)].Рекомендации Российской гастроэнтерологической ассоциации по диагностике и лечению гастроэзофагеальной рефлюксной болезни. 2020 г. [Recommendations of the Russian Gastroenterological Association for the diagnosis and treatment of gastroesophageal reflux disease. 2020 (In Russ.)].Sataloff RT, Castell DO, Katz PO, Sataloff DM. Reflux-laryngitis and related disorders. 3rd edition. Plural Publishing, Inc, San Diego, Oxford, 2006.Massawe WA, Nkya A, Abraham ZS, et al. Laryngopharyngeal reflux disease, prevalence and clinical characteristics in ENT department of a tertiary hospital Tanzania. World J Otorhinolaryngol Head Neck Surg. 2020;7(1):28-33. doi: 10.1016/j.wjorl.2020.04.009. PMID: 33474541; PMCID: PMC7801257Han H, Lyu Q, Zhao J. Laryngopharyngeal Reflux in Hypertrophic Laryngeal Diseases. Ear Nose Throat J. 2020; p. 145561320953232. doi: 10.1177/0145561320953232Reiter R, Heyduck A, Seufferlein T, et al. Laryngopharyngealer Reflux [Laryngopharyngeal Reflux]. Laryngorhinootologie. 2018;97(4):238-45. doi: 10.1055/s-0044-100794Włodarczyk E, Jetka T, Raj-Koziak D, et al. Diagnosis of laryngopharyngeal reflux in children with voice disorders using 24-hour pharyngeal pH monitoring. Int J Pediatr Otorhinolaryngol. 2019;121:188-96. doi: 10.1016/j.ijporl.2019.03.010Saniasiaya J, Kulasegarah J. Dysphonia and reflux in children: A systematic review. Int J Pediatr Otorhinolaryngol. 2020;139:110473. doi: 10.1016/j.ijporl.2020.110473Saniasiaya J, Kulasegarah J. Dysphonia and reflux in children: A systematic review. Int J Pediatr Otorhinolaryngol. 2020;139:110473. doi: 10.1016/j.ijporl.2020.110473Wertz A, Carroll LM, Zur KB. Pediatric laryngopharyngeal reflux: Perceptual, acoustic, and laryngeal findings. Int J Pediatr Otorhinolaryngol. 2020;133:109974. doi: 10.1016/j.ijporl.2020.109974De Bortoli N, Nacci A, Savarino E, et al. How many cases of laryngopharyngeal reflux suspected by laryngoscopy are gastroesophageal reflux disease-related? World J Gastroenterol. 2012;18(32):4363-70. doi: 10.3748/wjg.v18.i32.4363Abou-Ismail A, Vaezi MF. Evaluation of patients with suspected laryngopharyngeal reflux: a practical approach. Curr Gastroenterol Rep. 2011;13(3):213-8. doi: 10.1007/s11894-011-0184-xDrug VL, Cobzeanu D, Papaghiuc C, et al. Implicarea bolii de reflux gastroesofagian in patologia orl [Gastroesophageal reflux involvement in ENT disorders]. Rev Med Chir Soc Med Nat Iasi. 2005;109(2):220-2. PMID: 16607774Wang JS, Li JR. The role of laryngopharyngeal reflux in the pathogenesis of Reinke’s edema. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2016;30(24):1931-4. doi: 10.13201/j.issn.1001-1781.2016.24.007Wolford RW, Goyal A, Belgam Syed SY, Schaefer TJ. Pharyngitis. 2020 Nov 20. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021. PMID: 3013783Zeng S, Chen J, Wei X, et al. Clinical observation of the anti-reflux treatment for the chronic pharyngitis patients with the reflux finding score from 8 to 10. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2020;34(5):441-3. doi: 10.13201/j.issn.2096-7993.2020.05.013Yazici ZM, Sayin I, Kayhan FT, Biskin S. Laryngopharyngeal reflux might play a role on chronic nonspecific pharyngitis. Eur Arch Otorhinolaryngol. 2010;267(4):571-4. doi: 10.1007/s00405-009-1044-2Hwang MS, Forman SN, Kanter JA, Friedman M. Tonsillar Helicobacter pylori colonization in chronic tonsillitis: systematic review and meta-analysis. JAMA Otolaryngol Head Neck Surg. 2015;141(3):245-9. doi: 10.1001/jamaoto.2014.3296Siupsinskiene N, Katutiene I, Jonikiene V, et al. Helicobacter pylori in the tonsillar tissue: a possible association with chronic tonsillitis and laryngopharyngeal reflux. J Laryngol Otol. 2017;131(6):549-56. doi: 10.1017/S0022215117000597Kaptan ZK, Emir H, Uzunkulaoğlu H, et al. Determination of Helicobacter pylori in patients with chronic nonspecific pharyngitis. Laryngoscope. 2009;119(8):1479-83. doi: 10.1002/lary.20253Fancy T, Mathers PH, Ramadan HH. Otitis media with effusion: a possible role for Helicobacter pylori? Otolaryngol Head Neck Surg. 2009;140(2):256-8. doi: 10.1016/j.otohns.2008.11.023Karlidag T, Bulut Y, Keles E, et al. Detection of Helicobacter pylori in children with otitis media with effusion: a preliminary report. Laryngoscope. 2005;115(7):1262-5. doi: 10.1097/01.MLG.0000165697.83921.2BDu P, Zong S, Wen Y, et al. Association between Helicobacter pylori and otitis media with effusion in children: A systematic review. Int J Pediatr Otorhinolaryngol. 2020;135:110091. doi: 10.1016/j.ijporl.2020.110091Wu X, Zheng Y, Gao X, et al. Association Between Helicobacter pylori Infection and Otitis Media With Effusion Risk in Children: A Systematic Review and Meta-analysis. Otolaryngol Head Neck Surg. 2020;163(4):654-61. doi: 10.1177/0194599820921861Boronat-Echeverría N, Aguirre-Mariscal H, Carmolinga-Ponce M, et al. Helicobacter pylori detection and clinical symptomatology of gastroesophageal reflux disease in pediatric patients with otitis media with effusion. Int J Pediatr Otorhinolaryngol. 2016;87:126-9. doi: 10.1016/j.ijporl.2016.06.023Khasawneh L, Khassawneh AH, Kheirallah KA, et al. Otitis media with effusion: The role of Helicobacter Pylori in its pathogenesis. Ann Med Surg (Lond). 2021;62:278-82. doi: 10.1016/j.amsu.2021.01.056O’Reilly RC, He Z, Bloedon E, et al. The role of extraesophageal reflux in otitis media in infants and children. Laryngoscope. 2008;118(Suppl. 116):1-9. doi: 10.1097/MLG.0b013e31817924a3O’Reilly RC, Soundar S, Tonb D, et al. The role of gastric pepsin in the inflammatory cascade of pediatric otitis media. JAMA Otolaryngol Head Neck Surg. 2015;141(4):350-7. doi: 10.1001/jamaoto.2014.3581Abtahi SH, Kazerooni A, Brejis N, et al. Prevalence and characteristics of gastroesophageal reflux in children with otitis media in Isfahan, Iran. Adv Biomed Res. 2016;5:81. doi: 10.4103/2277-9175.182212Boers SA, de Zeeuw M, Jansen R, et al. Characterization of the nasopharyngeal and middle ear microbiota in gastroesophageal reflux-prone versus gastroesophageal reflux non-prone children. Eur J Clin Microbiol Infect Dis. 2018;37(5):851-7. doi: 10.1007/s10096-017-3178-2Huang YD, Tan JJ, Han XY, et al. Study on the correlation between adenoid hypertrophy and laryngopharyngeal reflux in children. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2018;32(12):899-904. doi: 10.13201/j.issn.1001-1781.2018.12.005Niu X, Wu ZH, Xiao XY, Chen X. The relationship between adenoid hypertrophy and gastroesophageal reflux disease: A meta-analysis. Medicine (Baltimore). 2018;97(41):e12540. doi: 10.1097/MD.0000000000012540Keles B, Ozturk K, Arbag H, et al. Frequency of pharyngeal reflux in children with adenoid hyperplasia. Int J Pediatr Otorhinolaryngol. 2005;69(8):1103-7. doi: 10.1016/j.ijporl.2005.02.019Johnston J, Mahadevan M, Douglas RG. Incidence and factors associated with revision adenoidectomy: A retrospective study. Int J Pediatr Otorhinolaryngol. 2017;103:125-8. doi: 10.1016/j.ijporl.2017.10.023Brietzke SE, Shin JJ, Choi S, et al. Clinical consensus statement: pediatric chronic rhinosinusitis. Otolaryngol Head Neck Surg. 2014;151(4):542-53. doi: 10.1177/0194599814549302Rosen R, Vandenplas Y, Singendonk M, et al. Pediatric gastroesophageal reflux clinical practice guidelines. J Pediatr Gastroenterol Nutr. 2018;66(3):516-54. doi: 10.1097/MPG.0000000000001889Goldsmith AJ, Rosenfeld RM. Treatment of pediatric sinusitis. Pediatr Clin N Am. 2003;50(2):413-26. doi: 10.1016/s0031-3955(03)00027-0El-Serag HB, Gilger M, Kuebeler M, Rabeneck L. Extraesophageal associations of gastroesophageal reflux disease in children without neurologic defects. Gastroenterology. 2001;121(6):1294-9. doi: 10.1053/gast.2001.29545Dewan K, Lieu J. A Clinical Trial of Proton Pump Inhibitors to Treat Children with Chronic Otitis Media with Effusion. J Int Adv Otol. 2018;14(2):245-9. doi: 10.5152/iao.2018.4286Bothwell MR, Parsons DS, Talbot A, et al. Outcome of reflux therapy on pediatric chronic sinusitis. Otolaryngol Head Neck Surg. 1999;121(3):255-62. doi: 10.1016/S0194-5998(99)70181-6Savarino E, Zentilin P, Marabotto E, et al. Drugs for improving esophageal mucosa defense: where are we now and where are we going? Ann Gastroenterol. 2017;30(6):585-91. doi: 10.20524/aog.2017.0187Gaffney J, Matou-Nasri S, Grau-Olivares M, Slevin M. Therapeutic applications of hyaluronan. Mol Biosyst. 2010; 6(3):437-43. doi: 10.1039/b910552mIalenti A, Di Rosa M. Hyaluronic acid modulates acute and chronic inflammation. Agents Actions. 1994; 43(1-2):44-7. doi: 10.1007/BF02005763Nolan A, Baillie C, Badminton J, et al. The efficacy of topical hyaluronic acid in the management of recurrent aphthous ulceration. J Oral Pathol Med. 2006;35:461-5. doi: 10.1111/j.1600-0714.2006.00433.xKim Y, Kessler SP, Obery DR, et al. Hyaluronan 35kDa treatment protects mice from Citrobacter rodentium infection and induces epithelial tight junction protein ZO-1 in vivo. Matrix Biol. 2017;62:28-39. doi: 10.1016/j.matbio.2016.11.001Volpi N. Anti-inflammatory activity of chondroitin sulphate: new functions from an old natural macromolecule. Inflammopharmacology. 2011;19(6):299-306. doi: 10.1007/s10787-011-0098-0Du Souich P, Garcia AG, Verges J, Montell E. Immunomodulatory and anti-inflammatory effects of chondroitin sulphate. J Cell Mol Med. 2009;13:1451-63. doi: 10.1111/j.1582-4934.2009.00826.xBonfils S, Dubrasquet M, Lambling A. The inhibition of peptic proteolysis by various polysaccharides. Rev Fr Etud Clin Biol. 1960;5:71-4Galzigna L, Previerocoletti MA. Action of sodium chondroitin sulfate on the enzymatic activity of pepsin. Gazz Med Ital. 1965;124:65-7Практические рекомендации всемирной гастроэнтерологической организации Дисфагия. Глобальные практические рекомендации и Каскады. Режим доступа: https://www.worldgastroenterology.org/UserFiles/file/guidelines/dysphagia-russian-2014.pdf. Ссылка активна на 29.03.2021 [Practical recommendations of the world gastroenterological organization Dysphagia. Global Best Practices and Cascades. Available at: https://www.worldgastroenterology.org/UserFiles/file/guidelines/dysphagia-russian-2014.pdf. Accessed: 29.03.2021 (In Russ.)].Lenzi G, Rapino P, Ferri S. On the behavior of gastric hydrochloric and peptic activity after administration of sodium chondroitin sulfate. Minerva Med. 1963;54:3421-4Ramya Devi D, Sandhya P, Vedha Hari BN. Poloxamer: a novel functional molecule for drug delivery and gene therapy. J Pharm Sci Res. 2013;5:159-65Dumortier G, Grossiord JL, Agnely F, Chaumeil JC. A review of poloxamer 407 pharmaceutical and pharmacological characteristics. Pharm Res. 2006; 23(12):2709-28. doi: 10.1007/s11095-006-9104-4Palmieri B, Corbascio D, Capone S, Lodi D. Preliminary clinical experience with a new natural compound in the treatment of esophagitis and gastritis: symptomatic effect. Trends Med. 2009;9:219-25Palmieri B, Merighi A, Corbascio D, et al. Fixed combination of hyaluronic acid and chondroitin-sulphate oral formulation in a randomized double blind, placebo controlled study for the treatment of symptoms in patients with non-erosive gastroesophageal reflux. Eur Rev Med Pharmacol Sci. 2013;17:3272-8Savarino V, Pace F, Scarpignato C, Esoxx Study Group Randomised clinical trial: mucosal protection combined with acid suppression in the treatment of non-erosive reflux disease – efficacy of Esoxx, a hyaluronic acid-chondroitin sulphate based bioadhesive formulation. Aliment Pharmacol Ther. 2017;45:631-42. doi: 10.1111/apt.13914