Noninvasive diagnosis of laryngopharyngeal reflux as an extraesophageal manifestation of gastroesophageal reflux disease: A literature review

Тo date, gastroesophageal reflux disease (GERD) is considered as a condition that includes various subgroups: erosive esophagitis, non-erosive reflux disease, Barrett’s esophagus, hypersensitive esophagus and functional heartburn. A common extraesophageal manifestation of GERD is laryngopharyngeal reflux (LFR), in which, in addition to dyspeptic symptoms, patients note hoarseness, cough, tickling and a feeling of a foreign body in the throat. When LFR occurs, the direct effect of gastroduodenal reflux on the mucous membrane of the larynx and pharynx leads to morphological changes, the development of pachyderma and laryngeal granuloma; indirect activation of reflex mechanisms causes the manifestation of esophagobronchial reflux. The diagnosis of LFR includes an analysis of the patient’s life history, registration of complaints using questionnaires (Index of reflux symptoms), assessment of the clinical and functional state of the larynx using a visually analog scale of reflux signs and videolaryngostroboscopy, the use of instrumental methods and laboratory tests. The detected laryngoscopic signs are not always pathognomonic for GERD-associated LFR: extraesophageal manifestations of the disease can also be observed in the absence of the most typical esophageal symptoms, which is a serious diagnostic problem. Due to the fact that not all instrumental diagnostic methods are informative in various cases of reflux-associated diseases, non-invasive methods are more convenient at the outpatient stage of patient examination questioning patients using special scales and questionnaires. The article presents the most informative and rational methods of noninvasive screening of GERD-associated diseases available in the available literature, aimed at identifying the severity of reflux manifestations, the level of patient satisfaction with their condition and the effectiveness of therapy. In order to improve the screening diagnostic process of LFR, it is necessary to develop and implement a reliable and sensitive questionnaire with an interdisciplinary approach.

1. Ivashkin VT, Maev IV, Trukhmanov AS, Lapina TL, Storonova OA, Zayratyants OV et al. Recommendations of the Russian Gastroenterological Association in diagnosis and treatment of gastroesophageal reflux disease. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2020;30(4):70–97. (In Russ.) https://doi.org/10.22416/1382-4376-2020-30-4-70-97.

2. Tsimmerman YaS, Vologzhanina LG. Gastroesophageal reflux disease: current views and prospects. Clinical Medicine (Russian Journal). 2016;94(7):485–496. (In Russ.) Available at: https://elibrary.ru/wjkyjf.

3. Tsukanov VV, Vasyutin AV, Butorin NN, Tonkikh YuL, Peretyatko OV, Pulikov AS. Prevalence and modern aspects of the treatment of patients with Barrett’s esophagus. Meditsinskiy Sovet. 2018;(14):24–27. (In Russ.) https://doi.org/10.21518/2079-701X-2018-14-24-27.

4. Maev IV, Barkalova EV, Ovsepian MA, Andreev DN. Phenotypes of gastroesophageal reflux disease: classification, pathogenesis and diagnostic criteria: A review. Consilium Medicum. 2022;24(5):277–285. (In Russ.) https://doi.org/10.26442/20751753.2022.5.201703.

5. Morozov SV, Kucheryavyy YuA. Treatment of patients with the non-erosive form of gastro ezofageal reflux disease. Contemporary view on the problem. Lechaschi Vrach. 2013;(7):32–41. (In Russ.) Available at: https://www.lvrach.ru/2013/07/15435750.

6. Barkalova EV, Kucheryavyy YuA, Ovsepian MA, Maev IV, Andreev DN. Heartburn in patients without esophagitis. Differential diagnosis. Experimental and Clinical Gastroenterology. 2018;(10):74–79. (In Russ.) Available at: https://www.nogr.org/jour/article/view/1065.

7. Maev IV, Samsonov AA, Andreev NG. Symptom of heartburn: habitual discomfort or a serious problem? Farmateka. 2011;(10):18–25. (In Russ.) Available at: https://pharmateca.ru/ru/archive/article/8150.

8. Abubakirova KE. Atypical options of the current gastroesophageal reflux disease. Vestnik KazNMU. 2013;(3-2):74–76. (In Russ.) Available at: https://kaznmu.edu.kz/press/wp-content/uploads/2013/05/АТИПИЧНЫЕВАРИАНТЫ-ТЕЧЕНИЯ-ГАСТРОЭЗОФАГЕАЛЬНОЙ-РЕФЛЮКСНОЙ-БОЛЕЗНИ.pdf.

9. Trukhan DI, Chusova NA, Drokina OV. Extraoesophageal symptoms of gastroesophageal reflux disease: laryngopharyngeal reflux in focus. Consilium Medicum. 2020;22(12):44–51. (In Russ.) https://doi.org/10.26442/20751753.2020.12.200559.

10. Maev IV, Kucheryavyy YuA. Advances in the diagnosis and treatment of gastroesophageal reflux disease. Farmateka. 2007;(2):49–52. (In Russ.) Available at: https://pharmateca.ru/ru/archive/article/6764.

11. Angotoeva IB, Aylarov AK, Kosyakov SYa, Loranskaya ID, Rumyantseva EE. Laryngopharyngeal reflux diagnostics: review article. Meditsinskiy Sovet. 2021;(15):48–57. (In Russ.) https://doi.org/10.21518/2079-701X-2021-15-48-57.

12. Ryabova MA, Ulupov MYu, Malkova ME. Risk factors for the development and recurrence of nonspecific laryngeal granuloma. RMJ. Medical Review. 2019;3(9-2):60–61. (In Russ.) Available at: https://www.rmj.ru/articles/otorinolaringologiya/Faktory_riska_razvitiya_i_recidiva_nespecificheskoy_granulemy_gortani/.

13. Angotoeva IB, Magomedova MM. Results of the study of conservative treatment of laryngeal manifestations of laryngopharyngeal reflux. Meditsinskiy Sovet. 2021;(18):28–33. (In Russ.) https://doi.org/10.21518/2079-701X-2021-18-28-33.

14. Angotoeva IB, Shchepkina EV, Magomedova MM. Clinical aspects of laryngopharyngeal reflux. Rossiiskaya Otorinolaringologiya. 2022;21(1):19–26. (In Russ.) https://doi.org/10.18692/1810-4800-2022-1-19-26.

15. Plotnikova EYu. “Masks” of gastroesophageal reflux disease. Laryngopharyngeal reflux. IDoctor. 2014;(6):28–31. (In Russ.) Available at: https://www.gastroscan.ru/literature/authors/7632.

16. Plotnikova EYu, Krasnova MV, Krasnov KA, Baranova EN. Laryngopharyngeal reflux in gastroenterological practice. Lechaschi Vrach. 2014;(2):61–65. (In Russ.) Available at: https://www.lvrach.ru/2014/02/15435897.

17. Boyenko SK, Yurenko EA, Platonov AS. Characteristics of the clinic and diagnostics of laryngopharyngeal reflux. Bulletin of Urgent and Recovery Surgery. 2020;5(3):14–22. (In Russ.) Available at: https://elibrary.ru/goaikq.

18. Maev IV, Selskaya YuV, Andreev DN, Dicheva DT, Bogolepova ZN, Kuznetsova EI. Laryngopharyngeal reflux: clinical significance, modern approaches to diagnosis and treatment. Meditsinskiy Sovet. 2019;(3):8–16. (In Russ.) https://doi.org/10.21518/2079-701X-2019-3-8-16.

19. Георгиева ЛВ, Карпищенко СА, Шумилова НА, Рябова МА, Тишков АВ, Страх ЛВ. Способ выявления и лечения фарингеального рефлюкса. Патент RU 2716486 C1, 11.03.2020.

20. Chandra KM, Harding SM. Therapy Insight: treatment of gastroesophageal reflux in adults with chronic cough. Nat Clin Pract Gastroenterol Hepatol. 2007;4(11):604–613. https://doi.org/10.1038/ncpgasthep0955.

21. Angotoeva IB, Denisenko NP, Sychev DA, Schepkina EV, Magomedova MM. Efficiency of treatment of laryngopharyngeal reflux with proton pump inhibitors depending on the CYP2C19 polymorphism. Meditsinskiy Sovet. 2021;(21-2):35–43. (In Russ.) https://doi.org/10.21518/2079-701X-2021-21-2-35-43.

22. Ryabova MA, Vasilevskiy DI, Filippov DI, Georgieva LV, Faizova AR. The effect of various forms of pharyngolaryngeal reflux on the larynx. Folia Otorhinolaryngologiae et Pathologiae Respiratoriae. 2020;26(3):70–80. (In Russ.) https://doi.org/10.33848/foliorl23103825-2020-26-3-70-80.

23. Kliaritskaia IL, Krivy VV, Rabotyagova YuS. Extra-esophageal manifestations of gastroesophageal reflux disease. Crimean Journal of Internal Diseases. 2019;(4):14–22. (In Russ.) Available at: http://crimtj.ru/Journal.files/2019-4/CrimeanTherJournal-4_2019.pdf.

24. Ribolsi M, Giordano A, Guarino MPL, Tullio A, Cicala M. New classifications of gastroesophageal reflux disease: an improvement for patient management? Expert Rev Gastroenterol Hepatol. 2019;13(8):761–769. https://doi.org/10.1080/17474124.2019.1645596.

25. Starostina SV, Makhov VM, Bolshakov AV. The role of functional and anatomical disorders of the esophagus and stomach in the development of laryngeal pathology: review article. Consilium Medicum. 2019;21(11):9–14. (In Russ.) Available at: https://consilium.orscience.ru/2075-1753/article/view/96769.

26. Saritas Yuksel E, Hong SK, Strugala V, Slaughter JC, Goutte M, Garrett CG et al. Rapid salivary pepsin test: blinded assessment of test performance in gastroesophageal reflux disease. Laryngoscope. 2012;122(6):1312–1316. https://doi.org/10.1002/lary.23252.

27. Du X, Wang F, Hu Z, Wu J, Wang Z, Yan C et al. The diagnostic value of pepsin detection in saliva for gastro-esophageal reflux disease: a preliminary study from China. BMC Gastroenterol. 2017;17(1):107. https://doi.org/10.1186/s12876-017-0667-9.

28. Angotoeva IB, Muldasheva AA. The enhancement of the efficacy of early diagnostics of laryngopharyngeal reflux. Vestnik Oto-Rino-Laringologii. 2015;80(1):60–62. (In Russ.) https://doi.org/10.17116/otorino201580160-62.

29. Starostina SV, Makhov VM, Storonova OA, Bolshakov AV, Kuprina IV, Trukhmanov AS, Ivashkin VT. Сapabilitу of 24-hour esophageal pH-impedance monitoring in the diagnosis of GERD-associated laryngeal diseases. Meditsinskiy Sovet. 2020;(16):62–72. (In Russ.) https://doi.org/10.21518/2079-701X-2020-16-62-72.

30. Kosyakov SYa, Loranskaya ID, Angotoeva IB, Muldasheva AA. Laryngopharyngeal reflux: yesterday, today and tomorrow. Meditsinskiy Sovet. 2016;(6):78–80. (In Russ.) https://doi.org/10.21518/2079-701X-2016-6-78-80.

31. Belafsky PC, Postma GN, Koufman JA. The validity and reliability of the reflux finding score (RFS). Laryngoscope. 2001;111(8):1313–1317. https://doi.org/10.1097/00005537-200108000-00001.

32. Rothman M, Farup C, Stewart W, Helbers L, Zeldis J. Symptoms associated with gastroesophageal reflux disease: development of a questionnaire for use in clinical trials. Dig Dis Sci. 2001;46(7):1540–1549. https://doi.org/10.1023/a:1010660425522.

33. Papakonstantinou L, Leslie P, Gray J, Chadwick T, Hudson M, Wilson JA. Laryngopharyngeal reflux: a prospective analysis of a 34 item symptom questionnaire. Clin Otolaryngol. 2009;34(5):455–459. https://doi.org/10.1111/j.1749-4486.2009.01998.x.

34. Williams RB, Szczesniak MM, Maclean JC, Brake HM, Cole IE, Cook IJ. Predictors of outcome in an open label, therapeutic trial of high-dose omeprazole in laryngitis. Am J Gastroenterol. 2004;99(5):777–785. https://doi.org/10.1111/j.1572-0241.2004.04151.x.

35. Ryabova MA, Shumilova NA, Georgieva LV, Tishkov AV. Screening method for diagnosis of pharyngolaryngeal reflux. Consilium Medicum. 2021;23(3):236–239. (In Russ.) Available at: https://consilium.orscience.ru/2075-1753/article/view/95447.

36. Velanovich V. The development of the GERD-HRQL symptom severity instrument. Dis Esophagus. 2007;20(2):130–134. https://doi.org/10.1111/j.1442-2050.2007.00658.x.

37. Ionova TI, Zinkovskaya AV, Mayevskaya EA, Nikitina TP, Porfirieva NM, Cheremushkina NV et al. Testing and validation of the Russian version of quality of life questionnaire in patients with GERD – GERD-HRQL. Terapevticheskii Arkhiv. 2020;92(12):59–66. (In Russ.) https://doi.org/10.26442/00403660.2020.12.200434.

38. Ionova TI, Nikitina TP, Mayevskaya EA, Cheremushkina NV, Shaburov RI, Kucheryavyy YuA, Maev IV. Development of the Russian version of quality of life questionnaire in patients with GERD – GERD-HRQL. Terapevticheskii Arkhiv. 2020;92(8):12–17. (In Russ.) https://doi.org/10.26442/00403660.2020.08.000658.

39. Jones R, Junghard O, Dent J, Vakil N, Halling K, Wernersson B, Lind T. Development of the GerdQ, a tool for the diagnosis and management of gastro-oesophageal reflux disease in primary care. Aliment Pharmacol Ther. 2009;30(10):1030–1038. https://doi.org/10.1111/j.1365-2036.2009.04142.x.

40. Kaibysheva VA, Kucheryavyy SA, Trukhmanov AS, Storonova OA, Konkov MA, Maev IV, Ivashkin VT. Results of a multicenter observational study on the application of the GerdQ international questionnaire for diagnosis of gastroesophageal reflux disease. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2013;23(5):15–24. (In Russ.) Available at: https://elibrary.ru/rflzyr.

41. Fass R, Zerbib F, Gyawali CP. AGA Clinical Practice Update on Functional Heartburn: Expert Review. Gastroenterology. 2020;158(8):2286–2293. https://doi.org/10.1053/j.gastro.2020.01.034.

42. Wang JY, Peng T, Zhao LL, Feng GJ, Liu YL. Poor consistency between reflux symptom index and laryngopharyngeal pH monitoring in laryngopharyngeal reflux diagnosis in Chinese population. Ann Transl Med. 2021;9(1):25. https://doi.org/10.21037/atm-20-4783.