Ларингофарингеальный рефлюкс как внепищеводное проявление гастроэзофагеальной рефлюксной болезни

1. Lechien JR, Vaezi MF, Chan WW, Allen JE, Karkos PD, Saussez S et al. The Dubai definition and diagnostic criteria of laryngopharyngeal reflux: The IFOS consensus. Laryngoscope. 2024;134(4):1614–24.

PMID: 37929860. https://doi.org/10.1002/lary.31134

2. Yadlapati R, Weissbrod P, Walsh E, Carroll TL, Chan WW, Gartner-Schmidt J et al. The San Diego consensus for laryngopharyngeal symptoms and laryngopharyngeal reflux disease. Am J Gastroenterol. 2025:10.14309/ajg.0000000000003482.

PMID: 40197644. PMCID: PMC12353988 (available on 2026-04-08). https://doi.org/10.14309/ajg.0000000000003482. Online ahead of print.

3. Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R; Global Consensus Group. The Montreal definition and classification of gastroesophageal reflux disease: A global evidence-based consensus. Am J Gastroenterol. 2006;101(8):1900–43.

PMID: 16928254. https://doi.org/10.1111/j.1572-0241.2006.00630.x

4. Chen JW, Vela MF, Peterson KA, Carlson DA. AGA clinical practice update on the diagnosis and management of extraesophageal gastroesophageal reflux disease: Expert review. Clin Gastroenterol Hepatol. 2023;21(6):1414–21.e3.

PMID: 37061897. https://doi.org/10.1016/j.cgh.2023.01.040

5. Spantideas N, Drosou E, Bougea A, Assimakopoulos D. Laryngopharyngeal reflux disease in the Greek general population, prevalence and risk factors. BMC Ear Nose Throat Disord. 2015;15:7.

PMID: 26696776. https://doi.org/10.1186/s12901-015-0020-2

6. Kamani T, Penney S, Mitra I, Pothula V. The prevalence of laryngopharyngeal reflux in the English population. Eur Arch Otorhinolaryngol. 2012;269(10):2219–25.

PMID: 22576243. https://doi.org/10.1007/s00405-012-2028-1

7. Sone M, Katayama N, Kato T, Izawa K, Wada M, Hamajima N et al. Prevalence of laryngopharyngeal reflux symptoms: Comparison between health checkup examinees and patients with otitis media. Otolaryngol Head Neck Surg. 2012;146(4):562–66.

PMID: 22287579. https://doi.org/10.1177/0194599811434049

8. Altman KW, Stephens RM, Lyttle CS, Weiss KB. Changing impact of gastroesophageal reflux in medical and otolaryngology practice. Laryngoscope. 2005;115(7):1145–53.

PMID: 15995499. https://doi.org/10.1097/01.MLG.0000165464.75164.E5

9. Lowden M, McGlashan JA, Steel A, Strugala V, Dettmar PW. Prevalence of symptoms suggestive of extra-oesophageal reflux in a general practice population in the UK. Logoped Phoniatr Vocol. 2009;34(1):32–35.

PMID: 19214865. https://doi.org/10.1080/14015430902735847

10. Yadlapati R, Katzka DA. Laryngopharyngeal reflux is an eternally rolling boulder. Clin Gastroenterol Hepatol. 2020;18(7):1431–32.

PMID: 31586647. https://doi.org/10.1016/j.cgh.2019.09.029

11. Liu K, Krause A, Yadlapati R. Quality of life and laryngopharyngeal reflux. Dig Dis Sci. 2023;68(9):3527–33.

PMID: 37410247. PMCID: PMC10726674. https://doi.org/10.1007/s10620-023-08027-8

12. Barillari MR, Giordano GM, Costa G, Caporusso E, Giumello F, Tolone S et al. Laryngopharyngeal reflux and psychological distress: A vicious cycle worth investigating. Eur Arch Otorhinolaryngol. 2025;282(6):3103–13.

PMID: 40258993. PMCID: PMC12122629. https://doi.org/10.1007/s00405-025-09313-z

13. Kahrilas PJ, Shaheen NJ, Vaezi MF, Hiltz SW, Black E, Modlin IM et al. American Gastroenterological Association Medical Position Statement on the management of gastroesophageal reflux disease. Gastroenterology. 2008;135(4):1383–91, 1391.e1–5.

PMID: 18789939. https://doi.org/10.1053/j.gastro.2008.08.045

14. Liu D, Qian T, Sun S, Jiang JJ. Laryngopharyngeal reflux and inflammatory responses in mucosal barrier dysfunction of the upper aerodigestive tract. J Inflamm Res. 2021;13:1291–304.

PMID: 33447069. PMCID: PMC7801919. https://doi.org/10.2147/JIR.S282809

15. Li FY, Li Y. Interleukin-6, desmosome and tight junction protein expression levels in reflux esophagitis-affected mucosa. World J Gastroenterol. 2009;15(29):3621–30.

PMID: 19653339. PMCID: PMC2721235. https://doi.org/10.3748/wjg.15.3621

16. Wood JM, Hussey DJ, Woods CM, Watson DI, Carney AS. Biomarkers and laryngopharyngeal reflux. J Laryngol Otol. 2011;125(12):1218–24.

PMID: 21914248. https://doi.org/10.1017/S0022215111002234

17. Gill GA, Johnston N, Buda A, Pignatelli M, Pearson J, Dettmar PW et al. Laryngeal epithelial defenses against laryngopharyngeal reflux: Investigations of E-cadherin, carbonic anhydrase isoenzyme III, and pepsin. Ann Otol Rhinol Laryngol. 2005;114(12):913–21.

PMID: 16425556. https://doi.org/10.1177/000348940511401204

18. Johnston N, Knight J, Dettmar PW, Lively MO, Koufman J. Pepsin and carbonic anhydrase isoenzyme III as diagnostic markers for laryngopharyngeal reflux disease. Laryngoscope. 2004;114(12):2129–34.

PMID: 15564833. https://doi.org/10.1097/01.mlg.0000149445.07146.03

19. Johnston N, Dettmar PW, Lively MO, Postma GN, Belafsky PC, Birchall M et al. Effect of pepsin on laryngeal stress protein (Sep70, Sep53, and Hsp70) response: Role in laryngopharyngeal reflux disease. Ann Otol Rhinol Laryngol. 2006;115(1):47–58.

PMID: 16466100. https://doi.org/10.1177/000348940611500108

20. Sasaki CT, Marotta J, Hundal J, Chow J, Eisen RN. Bile-induced laryngitis: Is there a basis in evidence? Ann Otol Rhinol Laryngol. 2005;114(3):192–97.

PMID: 15825567. https://doi.org/10.1177/000348940511400304

21. Lee JS, Jung AR, Park JM, Park MJ, Lee YC, Eun YG. Comparison of characteristics according to reflux type in patients with laryngopharyngeal reflux. Clin Exp Otorhinolaryngol. 2018;11(2):141–45.

PMID: 28993603. PMCID: PMC5951063. https://doi.org/10.21053/ceo.2017.00577

22. Lechien JR. Personalized treatments based on laryngopharyngeal reflux patient profiles: A narrative review. J Pers Med. 2023;13(11):1567.

PMID: 38003882. PMCID: PMC10671871. https://doi.org/10.3390/jpm13111567

23. Koufman JA, Aviv JE, Casiano RR, Shaw GY. Laryngopharyngeal reflux: position statement of the committee on speech, voice, and swallowing disorders of the American Academy of Otolaryngology-Head and Neck Surgery. Otolaryngol Head Neck Surg. 2002;127(1):32–35.

PMID: 12161727. https://doi.org/10.1067/mhn.2002.125760

24. Salihefendic N, Zildzic M, Cabric E. Laryngopharyngeal reflux disease – LPRD. Med Arch. 2017;71(3):215–18.

PMID: 28974837. PMCID: PMC5585794. https://doi.org/10.5455/medarh.2017.71.215-218

25. Campagnolo AM, Priston J, Thoen RH, Medeiros T, Assuncao AR. Laryngopharyngeal reflux: Diagnosis, treatment, and latest research. Int Arch Otorhinolaryngol. 2014;18(2):184–91.

PMID: 25992088. PMCID: PMC4297018. https://doi.org/10.1055/s-0033-1352504

26. Belafsky PC, Postma GN, Koufman JA. Validity and reliability of the reflux symptom index (RSI). J Voice. 2002;16(2):274–77.

PMID: 12150380. https://doi.org/10.1016/s0892-1997(02)00097-8

27. Lechien JR, Huet K, Finck C, Khalife M, Fourneau AF, Delvaux V et al. Validity and reliability of a French version of Reflux Symptom Index. J Voice. 2017;31(4):512.e1–512.e7.

PMID: 28069467. https://doi.org/10.1016/j.jvoice.2016.11.020

28. Schindler A, Mozzanica F, Ginocchio D, Peri A, Bottero A, Ottaviani F. Reliability and clinical validity of the Italian Reflux Symptom Index. J Voice. 2010;24(3):354–58.

PMID: 19303740. https://doi.org/10.1016/j.jvoice.2008.08.008

29. Lechien JR, Akst LM, Hamdan AL, Schindler A, Karkos PD, Barillari MR et al. Evaluation and management of laryngopharyngeal reflux disease: State of the art review. Otolaryngol Head Neck Surg. 2019;160(5):762–82.

PMID: 30744489. https://doi.org/10.1177/0194599819827488

30. Lechien JR, Schindler A, Hamdan AL, Bobin F, Barillari MR, Harmegnies B et al. The development of new clinical instruments in laryngopharyngeal reflux disease: The international project of young otolaryngologists of the International Federation of Oto-rhino-laryngological Societies. Eur Ann Otorhinolaryngol Head Neck Dis. 2018;135(5S):S85–S91.

PMID: 30170971. https://doi.org/10.1016/j.anorl.2018.05.013

31. (Runggaldier D, Hente J, Brockmann-Bauser M, Pohl D, Bohlender JE. Current possibilities and challenges in the diagnosis of laryngopharyngeal reflux. HNO. 2021;69(11):861–67 (In German)).

PMID: 33619606. https://doi.org/10.1007/s00106-021-01006-3

32. Belafsky PC, Postma GN, Koufman JA. The validity and reliability of the reflux finding score (RFS). Laryngoscope. 2001;111(8):1313–17.

PMID: 11568561. https://doi.org/10.1097/00005537-200108000-00001

33. Lechien JR, Rodriguez Ruiz A, Dequanter D, Bobin F, Mouawad F, Muls V et al. Validity and reliability of the reflux sign assessment. Ann Otol Rhinol Laryngol. 2020;129(4):313–25.

PMID: 31729247. https://doi.org/10.1177/0003489419888947

34. Vardar R, Varis A, Bayrakci B, Akyildiz S, Kirazli T, Bor S. Relationship between history, laryngoscopy and esophagogastroduodenoscopy for diagnosis of laryngopharyngeal reflux in patients with typical GERD. Eur Arch Otorhinolaryngol. 2012;269(1):187–91.

PMID: 21881998. https://doi.org/10.1007/s00405-011-1748-y

35. Lechien JR, Bobin F, Muls V, Eisendrath P, Horoi M, Thill MP et al. Gastroesophageal reflux in laryngopharyngeal reflux patients: Clinical features and therapeutic response. Laryngoscope. 2020;130(8):E479–E489.

PMID: 31876296. https://doi.org/10.1002/lary.28482

36. Lee YC, Kwon OE, Park JM, Eun YG. Do laryngoscopic findings reflect the characteristics of reflux in patients with laryngopharyngeal reflux? Clin Otolaryngol. 2018;43(1):137–43.

PMID: 28605121. https://doi.org/10.1111/coa.12914

37. Becker V, Graf S, Schlag C, Schuster T, Feussner H, Schmid RM et al. First agreement analysis and day-to-day comparison of pharyngeal pH monitoring with pH/ impedance monitoring in patients with suspected laryngopharyngeal reflux. J Gastrointest Surg. 2012;16(6):1096–101.

PMID: 22450948. https://doi.org/10.1007/s11605-012-1866-x

38. Masaany M, Marina MB, Sharifa Ezat WP, Sani A. Empirical treatment with pantoprazole as a diagnostic tool for symptomatic adult laryngopharyngeal reflux. J Laryngol Otol. 2011;125(5):502–8.

PMID: 21356141. https://doi.org/10.1017/S0022215111000120

39. Tseng D, Rizvi AZ, Fennerty MB, Jobe BA, Diggs BS, Sheppard BC et al. Forty-eight-hour pH monitoring increases sensitivity in detecting abnormal esophageal acid exposure. J Gastrointest Surg. 2005;9(8):1043–52.

PMID: 16269374. https://doi.org/10.1016/j.gassur.2005.07.011

40. Zhang M, Chia C, Stanley C, Phyland DJ, Paddle PM. Diagnostic utility of salivary pepsin as compared with 24-hour dual pH/ impedance probe in laryngopharyngeal reflux. Otolaryngol Head Neck Surg. 2021;164(2):375–80.

PMID: 32895009. https://doi.org/10.1177/0194599820951183

41. (Wang JS, Li JR. A comparison of pH <4 and pH <5 as thresholds for 24-hour pH monitoring in the diagnosis of laryngopharyngeal reflux. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2016;51(9):661–65 (In Chinese)).

PMID: 27666703. https://doi.org/10.3760/cma.j.issn.1673-0860.2016.09.005

42. Сторонова О.А., Параскевова А.В., Трухманов А.С., Ивашкин В.Т. Характеристики ларингофарингеального рефлюкса, выявленные методом рН-импедансометрии у больных ГЭРБ без внепищеводных проявлений. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2023;33(5 прил. 62):6. (Storonova OA, Paraskevova AV, Trukhmanov AS, Ivashkin VT. Characteristics of laryngopharyngeal reflux detected by pH-impedancemetry in patients with GERD without extraesophageal manifestations. Rossiyskiy zhurnal gastroenterologii, gepatologii, koloproktologii = Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2023;33(5 Suppl. 62):6 (In Russ.)).

43. (Runggaldier D, Pohl D. Chronic cough – what role do PPIs play? Inf Arzt. 2017;2017(6):27 (In German)).

44. Knight J, Lively MO, Johnston N, Dettmar PW, Koufman JA. Sensitive pepsin immunoassay for detection of laryngopharyngeal reflux. Laryngoscope. 2005;115(8):1473–78.

PMID: 16094128. https://doi.org/10.1097/01.mlg.0000172043.51871.d9

45. Samuels TL, Johnston N. Pepsin as a marker of extraesophageal reflux. Ann Otol Rhinol Laryngol. 2010;119(3):203–8.

PMID: 20392035. https://doi.org/10.1177/000348941011900310

46. Rao YF, Wang J, Cheng DN, Xu Y, Ren X, Yang W et al. The controversy of pepsinogen A/ pepsin a in detecting extra-gastroesophageal reflux. J Voice. 2023;37(5):748–56.

PMID: 34090740. https://doi.org/10.1016/j.jvoice.2021.04.009

47. Abdallah AF, El-Desoky T, Fathi K, Elkashef WF, Zaki A. Clinical utility of bronchoalveolar lavage pepsin in diagnosis of gastroesophageal reflux among wheezy infants. Can Respir J. 2016;2016:9480843.

PMID: 27516725. PMCID: PMC4969502. https://doi.org/10.1155/2016/9480843

48. Wang YJ, Lang XQ, Wu D, He YQ, Lan CH, Xiao X et al. Salivary pepsin as an intrinsic marker for diagnosis of sub-types of gastroesophageal reflux disease and gastroesophageal reflux disease-related disorders. J Neurogastroenterol Motil. 2020;26(1):74–84.

PMID: 31650768. PMCID: PMC6955190. https://doi.org/10.5056/jnm19032

49. Wang J, Zhao Y, Ren J, Xu Y. Pepsin in saliva as a diagnostic biomarker in laryngopharyngeal reflux: A meta-analysis. Eur Arch Otorhinolaryngol. 2018;275(3):671–78.

PMID: 29238875. https://doi.org/10.1007/s00405-017-4845-8

50. Guo Z, Jiang J, Wu H, Zhu J, Zhang S, Zhang C. Salivary peptest for laryngopharyngeal reflux and gastroesophageal reflux disease: A systemic review and meta-analysis. Medicine (Baltimore). 2021;100(32):e26756.

PMID: 34397878. PMCID: PMC8360476. https://doi.org/10.1097/MD.0000000000026756

51. Ивашкин В.Т., Трухманов А.С., Маев И.В., Драпкина О.М., Ливзан М.А., Мартынов А.И. с соавт. Диагностика и лечение гастроэзофагеальной рефлюксной болезни (Рекомендации Российской гастроэнтерологической ассоциации, Российского научного медицинского общества терапевтов, Российского общества профилактики неинфекционных заболеваний, Научного сообщества по изучению микробиома человека). Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2024;34(5):111–135. (Ivashkin VT, Trukhmanov AS, Maev IV, Drapkina OM, Livzan MA, Martynov AI et al. Diagnosis and treatment of gastroesophageal reflux disease (Clinical guidelines of the Russian Gastroenterological Association, Russian Scientific Medical Society of Internal Medicine, Russian Society for the Prevention of Noncommunicable Diseases, Scientific Сommunity for Human Microbiome Research). Rossiyskiy zhurnal gastroenterologii, gepatologii, koloproktologii = Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2024;34(5):111–135 (In Russ.)).

EDN: BPZIFZ. https://doi.org/10.22416/1382-4376-2024-34-5-111-135

52. Qadeer MA, Phillips CO, Lopez AR, Steward DL, Noordzij JP, Wo JM et al. Proton pump inhibitor therapy for suspected GERD-related chronic laryngitis: A meta-analysis of randomized controlled trials. Am J Gastroenterol. 2006;101(11):2646–54.

PMID: 17037995. https://doi.org/10.1111/j.1572-0241.2006.00844.x

53. Wei C. A meta-analysis for the role of proton pump inhibitor therapy in patients with laryngopharyngeal reflux. Eur Arch Otorhinolaryngol. 2016;273(11):3795–801.

PMID: 27312992. https://doi.org/10.1007/s00405-016-4142-y

54. Бордин Д.С., Андреев Д.Н., Маев И.В. Эффективность эзофагопротекции в комплексном лечении эрозивной формы гастроэзофагеальной рефлюксной болезни: систематический обзор и метаанализ контролируемых исследований. Терапевтический архив. 2022;94(12):1407–1412. (Bordin DS, Andreev DN, Maev IV. Efficacy of esophagus protection in complex treatment of erosive gastroesophageal reflux disease: A systematic review and meta-analysis of controlled trials. Terapevticheskiy arkhiv = Therapeutic Archive. 2022;94(12):1407–1412 (In Russ.)).

EDN: KIZTWE. https://doi.org/10.26442/00403660.2022.12.202011

55. Bordin DS, Livzan MA, Mozgovoi SI, Gaus OV, Lapteva IV. The mucosal protection in the treatment of erosive reflux esophagitis: Mechanisms for restoring epithelial permeability. A randomized clinical trial. J Gastrointestin Liver Dis. 2024;33(4):455–62.

. PMID: 39733305. https://doi.org/10.15403/jgld-5859

56. Лаптева И.В., Федорин М.М., Нестерова К.И., Ливзан М.А., Мозговой С.И. Возможности терапии эзофагопротектором в ведении больного ГЭРБ с внепищеводными проявлениями. РМЖ. Медицинское обозрение. 2022;6(5):237–243. (Lapteva IV, Fedorin MM, Nesterova KI, Livzan MA, Mozgovoi SI. Therapy with esophageal protector in the management of GERD with extraesophageal symptoms. Russkiy meditsinskiy zhurnal. Meditsinskoye obozreniye = Russian Medical Inquiry. 2022;6(5):237–243 (In Russ.)).

EDN: WMVMBD. https://doi.org/10.32364/2587-6821-2022-6-5-237-243

57. Shetty RR, Burde KN, Guttal KS. The efficacy of topical hyaluronic acid 0.2% in the management of symptomatic oral lichen planus. J Clin Diagn Res. 2016;10(1):ZC46–50.

PMID: 26894175. PMCID: PMC4740703. https://doi.org/10.7860/JCDR/2016/15934.7101

58. Lee JH, Jung JY, Bang D. The efficacy of topical 0.2% hyaluronic acid gel on recurrent oral ulcers: Comparison between recurrent aphthous ulcers and the oral ulcers of Behçet’s disease. Acad Dermatol Venereol. 2008;22(5):590–95.

PMID: 18093111. https://doi.org/10.1111/j.1468-3083.2007.02564.x

59. Palmieri B, Corbascio D, Capone S, Lodi D. Preliminary clinical experience with a new natural compound in the treatment of oesophagitis and gastritis: Symptomatic effect. Trends Med. 2009;9(4):219–25.

60. Chmielecka-Rutkowska J, Tomasik B, Pietruszewska W. The role of oral formulation of hyaluronic acid and chondroitin sulphate for the treatment of the patients with laryngopharyngeal reflux. Otolaryngol Pol. 2019;73(6):38–49.

PMID: 31823839. https://doi.org/10.5604/01.3001.0013.5776

61. Pellegatta G, Mangiavillano B, Semeraro R, Auriemma F, Carlani E, Fugazza A et al. The effect of hyaluronic acid and chondroitin sulphate-based medical device combined with acid suppression in the treatment of atypical symptoms in gastroesophageal reflux disease. J Clin Med. 2022;11(7):1890.

PMID: 35407497. PMCID: PMC9000081. https://doi.org/10.3390/jcm11071890

62. Кучерявый Ю.А., Андреев Д.Н., Еремина Е.Ю., Гильманов А.А., Назарова О.В., Сиднева Е.А. с соавт. Эффективность использования эзофагопротектора в рамках лечения гастроэзофагеальной рефлюксной болезни с экстраэзофагеальной симптоматикой: открытое наблюдательное многоцентровое исследование. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2022;32(4):38–49. (Kucheryavy YuA, Andreyev DN, Eryomina EYu, Gilmanov AA, Nazarova OV, Sidneva YeA. et al. Efficacy of esophageal protector in treating gastroesophageal reflux disease with extraesophageal symptoms: A multicenter, open-label, observational study. Rossiyskiy zhurnal gastroenterologii, gepatologii, koloproktologii = Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2022;32(4):38–49 (In Russ.)).

EDN: OUIIEG. https://doi.org/10.22416/1382-4376-2022-32-4-38-49

63. Limb M, Connor A, Pickford M, Church A, Mamman R, Reader S et al. Scintigraphy can be used to compare delivery of sore throat formulations. Int J Clin Pract. 2009;63(4):606–12.

PMID: 19222617. https://doi.org/10.1111/j.1742-1241.2008.01984.x

64. Pellegatta G, Spadaccini M, Lamonaca L, Craviotto V, D’Amico F, Ceriotti L et al. Evaluation of human esophageal epithelium permeability in presence of different formulations containing hyaluronic acid and chondroitin sulphate. Med Devices (Auckl). 2020;13:57–66.

PMID: 32210642. PMCID: PMC7069498. https://doi.org/10.2147/MDER.S234810