Фенотипы гастроэзофагеальной рефлюксной болезни: классификация, механизмы развития и критерии диагностики

1. Drossman DA Functional gastrointestinal disorders: history, pathophysiology, clinical features and Rome IV. Gastroenterology. 2016;150:1262-79. DOI:10.1053/j.gastro.2016.02.032.0.1053/j.gastro.2016.02.032
2. Маев И.В., Бусарова Г.А., Андреев Д.Н. Болезни пищевода. М.: ГЭОТАР-Медиа, 2019 [Maev IV, Busarova GA, Andreev DN. Bolezni pishchevoda. Moscow: GEOTAR-Media, 2019 (in Russian)].
3. Zheng Z, Shang Y, Wang N, et al. Current Advancement on the Dynamic Mechanism of Gastroesophageal Reflux Disease. Int J Biol Sci. 2021;17(15):4154-64. DOI:10.7150/ijbs.65066
4. Исаков В.А., Морозов С.В., Ставраки Е.С., и др. Анализ распространенности изжоги: национальное эпидемиологическое исследование взрослого городского населения (АРИАДНА). Экспериментальная и клиническая гастроэнтерология. 2008;1:20-30 [Isakov VA, Morozov SV, Stavraki ES, et al. Analiz rasprostranennosti izzhogi: natsional'noe epidemiologicheskoe issledovanie vzroslogo gorodskogo naseleniia (ARIADNA). Eksperimental'naia i klinicheskaia gastroenterologiia. 2008;1:20-30 (in Russian)].
5. Ивашкин В.Т., Маев И.В., Трухманов А.С., и др. Рекомендации Российской гастроэнтерологической ассоциации по диагностике и лечению гастроэзофагеальной рефлюксной болезни. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2020;30(4):70-97 [Ivashkin VT, Maev IV, Trukhmanov AS, 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 Russian)]. DOI:10.22416/1382-4376-2020-30-4-70-97
6. Ribolsi M, Giordano A, Guarino MPL, et al. New classifications of gastroesophageal reflux disease: an improvement for patient management? Expert Rev. Gastroenterol Hepatol. 2019;13(8):761-9. DOI:10.1080/17474124.2019.1645596
7. Savarino E, Zentilin P, Tutuian R, et al. The role of nonacid reflux in NERD: lessons learned fr om impedance-pH monitoring in 150 patients off therapy. Am J Gastroenterol. 2008;103(11):2685-93. DOI:10.1111/j.1572-0241.2008.02119.x
8. Savarino E, Tutuian R, Zentilin P, et al. Characteristics of reflux episodes and symptom association in patients with erosive esophagitis and nonerosive reflux disease: study using combined impedance-pH off therapy. Am J Gastroenterol. 2010;105(5):1053-61. DOI:10.1038/ajg.2009.670
9. Shinozaki S, Osawa H, Hayashi Y, et al. Long-term vonoprazan therapy is effective for controlling symptomatic proton pump inhibitor-resistant gastroesophageal reflux disease. Biomed Rep. 2021;14(3):32. DOI:10.3892/br.2021.1408
10. Lundell LR, Dent J, Bennett JR, et al. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut. 1999;45(2):172-80. DOI:10.1136/gut.45.2.172
11. Dent J, Becher A, Sung J, et al. Systematic review: patterns of reflux-induced symptoms and esophageal endoscopic findings in large-scale surveys. Clin Gastroenterol Hepatol. 2012;10(8):863-73.e3. DOI:10.1016/j.cgh.2012.02.028
12. Modlin IM, Hunt RH, Malfertheiner P, et al. Diagnosis and management of non-erosive reflux disease--the Vevey NERD Consensus Group. Digestion. 2009;80(2):74-88. DOI:10.1159/000219365
13. Patel A, Sayuk GS, Kushnir VM, et al. GERD phenotypes from pH-impedance monitoring predict symptomatic outcomes on prospective evaluation. Neurogastroenterol Motil. 2016;28(4):513-21. DOI:10.1111/nmo.12745
14. Gyawali CP, Kahrilas PJ, Savarino E, et al. Modern diagnosis of GERD: the Lyon Consensus. Gut. 2018;67(7):1351-62. DOI:10.1136/gutjnl-2017-314722
15. Yamasaki T, Fass R. Reflux Hypersensitivity: A New Functional Esophageal Disorder. J Neurogastroenterol Motil. 2017;23(4):495-503. DOI:10.5056/jnm17097
16. Fass R, Zerbib F, Gyawali CP. AGA Clinical Practice Update on Functional Heartburn: Expert Review. Gastroenterology. 2020;158(8):2286-93. DOI:10.1053/j.gastro.2020.01.034
17. Clouse RE, Richter JE, Heading RC, et al. Functional esophageal disorders. Gut. 1999;45 Suppl 2(Suppl. 2):II31-6. DOI:10.1136/gut.45.2008.ii31
18. Patel D, Fass R, Vaezi M. Untangling Nonerosive Reflux Disease From Functional Heartburn. Clin Gastroenterol Hepatol. 2021;19(7):1314-26. DOI:10.1016/j.cgh.2020.03.057
19. Quigley EM. Non-erosive reflux disease, functional heartburn and gastroesophageal reflux disease; insights into pathophysiology and clinical presentation. Chin J Dig Dis. 2006;7(4):186-90. DOI:10.1111/j.1443-9573.2006.00266.x
20. Savarino V, Marabotto E, Zentilin P, et al. Esophageal reflux hypersensitivity: Non-GERD or still GERD? Dig Liver Dis. 2020;52(12):1413-20. DOI:10.1016/j.dld.2020.10.003
21. Xu C, Niu X. Progress on the Mechanism of Visceral Hypersensitivity in Nonerosive Reflux Disease. Gastroenterol Res Pract. 2022;2022:4785077. DOI:10.1155/2022/4785077
22. Souza RF, Huo X, Mittal V, et al. Gastroesophageal reflux might cause esophagitis through a cytokine-mediated mechanism rather than caustic acid injury. Gastroenterology. 2009;137(5):1776-84. DOI:10.1053/j.gastro.2009.07.055
23. Kondo T, Oshima T, Tomita T, et al. Prostaglandin E(2) mediates acid-induced heartburn in healthy volunteers. Am J Physiol Gastrointest Liver Physiol. 2013;304(6):G568-73. DOI:10.1152/ajpgi.00276.2012
24. Sei H, Oshima T, Shan J, et al. Esophageal Epithelial-Derived IL-33 Is Upregulated in Patients with Heartburn. PLoS One. 2016;11(4):e0154234. DOI:10.1371/journal.pone.0154234
25. Shan J, Oshima T, Fukui H, et al. Acidic deoxycholic acid and chenodeoxycholic acid induce interleukin-8 production through p38 mitogen-activated protein kinase and protein kinase A in a squamous epithelial model. J Gastroenterol Hepatol. 2013;28(5):823-8. DOI:10.1111/jgh.12139
26. Симаненков В.И., Маев И.В., Ткачева О.Н., и др. Синдром повышенной эпителиальной проницаемости в клинической практике. Мультидисциплинарный национальный консенсус. Кардиоваскулярная терапия и профилактика. 2021;20(1):2758 [Simanenkov VI, Maev IV, Tkacheva ON, et al. Syndrome of increased epithelial permeability in clinical practice. Multidisciplinary national Consensus. Cardiovascular Therapy and Prevention. 2021;20(1):2758 (in Russian)].
27. Kondo T, Miwa H. The Role of Esophageal Hypersensitivity in Functional Heartburn. J Clin Gastroenterol. 2017;51(7):571-8. DOI:10.1097/MCG.0000000000000885
28. Dickman R, Maradey-Romero C, Fass R. The role of pain modulators in esophageal disorders – no pain no gain. Neurogastroenterol Motil. 2014;26(5):603-10. DOI:10.1111/nmo.12339
29. Siwiec RM, Babaei A, Kern M, et al. Esophageal acid stimulation alters insular cortex functional connectivity in gastroesophageal reflux disease. Neurogastroenterol Motil. 2015;27(2):201-11. DOI:10.1111/nmo.12464
30. Wang P, Du C, Chen FX, et al. BDNF contributes to IBS-like colonic hypersensitivity via activating the enteroglia-nerve unit. Sci Rep. 2016;6:20320. DOI:10.1038/srep20320
31. Wouters MM, Vicario M, Santos J. The role of mast cells in functional GI disorders. Gut. 2016;65(1):155-68. DOI:10.1136/gutjnl-2015-309151
32. Xu X, Li Z, Zou D, et al. High expression of calcitonin gene-related peptide and substance P in esophageal mucosa of patients with non-erosive reflux disease. Dig Dis Sci. 2013;58(1):53-60. DOI:10.1007/s10620-012-2308-z
33. Wulamu W, Yisireyili M, Aili A, et al. Chronic stress augments esophageal inflammation, and alters the expression of transient receptor potential vanilloid 1 and protease-activated receptor 2 in a murine model. Mol Med Rep. 2019;19(6):5386-96. DOI:10.3892/mmr.2019.10192
34. Knowles CH, Aziz Q. Visceral hypersensitivity in non-erosive reflux disease. Gut. 2008;57(5):674-83. DOI:10.1136/gut.2007.127886
35. Silva RO, Bingana RD, Sales TMAL, et al. Role of TRPV1 receptor in inflammation and impairment of esophageal mucosal integrity in a murine model of nonerosive reflux disease. Neurogastroenterol Motil. 2018:e13340. DOI:10.1111/nmo.13340
36. Holzer P. Acid-sensing ion channels in gastrointestinal function. Neuropharmacology. 2015;94:72-9. DOI:10.1016/j.neuropharm.2014.12.009
37. Yan J, Edelmayer RM, Wei X, et al. Dural afferents express acid-sensing ion channels: a role for decreased meningeal pH in migraine headache. Pain. 2011;152(1):106-113. DOI:10.1016/j.pain.2010.09.036
38. Choi JM, Yang JI, Kang SJ, et al. Association Between Anxiety and Depression and Gastroesophageal Reflux Disease: Results From a Large Cross-sectional Study. J Neurogastroenterol Motil. 2018;24(4):593-602. DOI:10.5056/jnm18069
39. Chen X, Li P, Wang F, et al. Psychological Results of 438 Patients with persisting Gastroesophageal Reflux Disease Symptoms by Symptom Checklist 90-Revised Questionnaire. Euroasian J Hepatogastroenterol. 2017;7(2):117-21. DOI:10.5005/jp-journals-10018-1230
40. Rengarajan A, Pomarat M, Zerbib F, et al. Overlap of functional heartburn and reflux hypersensitivity with proven gastroesophageal reflux disease. Neurogastroenterol Motil. 2021;33(6):e14056. DOI:10.1111/nmo.14056
41. Broers C, Melchior C, Van Oudenhove L, et al. The effect of intravenous corticotropin-releasing hormone administration on esophageal sensitivity and motility in health. Am J Physiol Gastrointest Liver Physiol. 2017;312(5):G526-34. DOI:10.1152/ajpgi.00437.2016
42. Yamasaki T, Tomita T, Takimoto M, et al. Intravenous Corticotropin-releasing Hormone Administration Increases Esophageal Electrical Sensitivity in Healthy Individuals. J Neurogastroenterol Motil. 2017;23(4):526-32. DOI:10.5056/jnm17067
43. Broers C, Geeraerts A, Boecxstaens V, et al. The role of serotonin in the control of esophageal sensitivity assessed by multimodal stimulation in health. Neurogastroenterol Motil. 2021;33(3):e14057. DOI:10.1111/nmo.14057
44. Pourhamzeh M, Moravej FG, Arabi M, et al. The Roles of Serotonin in Neuropsychiatric Disorders. Cell Mol Neurobiol. 2022;42(6):1671-92. DOI:10.1007/s10571-021-01064-9
45. Lei WY, Chang WC, Wong MW, et al. Sleep Disturbance and Its Association with Gastrointestinal Symptoms/Diseases and Psychological Comorbidity. Digestion. 2019;99(3):205-12. DOI:10.1159/000490941
46. Xu J, Gao H, Zhang L, et al. Melatonin alleviates cognition impairment by antagonizing brain insulin resistance in aged rats fed a high-fat diet. J Pineal Res. 2019;67(2):e12584. DOI:10.1111/jpi.12584
47. Jiang H, Ling Z, Zhang Y, et al. Altered fecal microbiota composition in patients with major depressive disorder. Brain Behav Immun. 2015;48:186-94. DOI:10.1016/j.bbi.2015.03.016
48. Zheng P, Zeng B, Zhou C, et al. Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host's metabolism. Mol Psychiatry. 2016;21(6):786-96. DOI:10.1038/mp.2016.44
49. D'Souza SM, Houston K, Keenan L, et al. Role of microbial dysbiosis in the pathogenesis of esophageal mucosal disease: A paradigm shift from acid to bacteria? World J Gastroenterol. 2021;27(18):2054-72. DOI:10.3748/wjg.v27.i18.2054
50. Savarino E, Pohl D, Zentilin P, et al. Functional heartburn has more in common with functional dyspepsia than with non-erosive reflux disease. Gut. 2009;58(9):1185-91. DOI:10.1136/gut.2008.175810
51. Kushnir VM, Sathyamurthy A, Drapekin J, et al. Assessment of concordance of symptom reflux association tests in ambulatory pH monitoring. Aliment Pharmacol Ther. 2012;35:1080-7. DOI:10.1111/j.1365-2036.2012.05066.x
52. Маев И.В., Баркалова Е.В., Овсепян М.А., и др. Возможности рН-импедансометрии и манометрии высокого разрешения при ведении пациентов с рефрактерной гастроэзофагеальной рефлюксной болезнью. Терапевтический архив. 2017;89(2):76-83 [Maev IV, Barkalova EV, Ovsepyan MA, et al. Possibilities of pH impedance and high-resolution manometry in managing patients with refractory gastroesophageal reflux disease. Terapevticheskii Arkhiv (Ter. Arkh.). 2017;89(2):76-83 (in Russian)].
53. Баркалова Е.В., Кучерявый Ю.А., Овсепян М.А., Маев И.В. Изжога у больных без эзофагита: дифференциальная диагностика. Экспериментальная и клиническая гастроэнтерология. 2018;158(10):74-9 [Barkalova EV, Kucheryavyy YuA, Ovsepian MA, Maev IV. Heartburn in patients without esophagitis. Differential diagnosis. Experimental and clinical gastroenterology. 2018;158(10):74-9 (in Russian)]. DOI:10.31146/1682-8658-ecg-158-10-74-79
54. Savarino E, Gemignani L, Pohl D, et al. Oesophageal motility and bolus transit abnormalities increase in parallel with the severity of gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2011;34:476-86. DOI:10.1111/j.1365-2036.2011.04742.x
55. Маев И.В., Самсонов А.А., Андреев Д.Н. Клиническое значение синдрома «перекреста» функциональной диспепсии и гастроэзофагеальной рефлюксной болезни. Клинические перспективы гастроэнтерологии, гепатологии. 2013;5:17-22 [Maev IV, Samsonov AA, Andreev DN. Klinicheskoe znachenie sindroma "perekresta" funktsional'noi dispepsii i gastroezofageal'noi refliuksnoi bolezni. Klinicheskie perspektivy gastroenterologii, gepatologii. 2013;5:17-22 (in Russian)].
56. Маев И.В., Андреев Д.Н., Дичева Д.Т., и др. Функциональная диспепсия: современное состояние проблемы. Медицинский вестник МВД. 2013;4:38-45 [Maev IV, Andreev DN, Dicheva DT, et al. Funktsional'naia dispepsiia: sovremennoe sostoianie problemy. Meditsinskii vestnik MVD. 2013;4:38-45 (in Russian)].
57. Маев И.В., Дичева Д.Т., Андреев Д.Н. Подходы к индивидуализации лечения гастроэзофагеальной рефлюксной болезни. Эффективная фармакотерапия. Гастроэнтерология. 2012;4:18-22 [Maev IV, Dicheva DT, Andreev DN. Podkhody k individualizatsii lecheniia gastroezofageal'noi refliuksnoi bolezni. Effektivnaia farmakoterapiia. Gastroenterologiia. 2012;4:18-22 (in Russian)].
58. Маев И.В., Самсонов А.А., Андреев Д.Н., Кочетов С.А. Дифференцированная тактика лечения синдрома функциональной диспепсии. Медицинский совет. 2012;9:13-20 [Mayev IV, Samsonov AA, Andreev DN, Kochetov SA. Differentiated treatment of functional dyspepsia syndrome. Meditsinskii sovet. 2012;9:13-20 (in Russian)].
59. Abdallah J, George N, Yamasaki T, et al. Most Patients With Gastroesophageal Reflux Disease Who Failed Proton Pump Inhibitor Therapy Also Have Functional Esophageal Disorders. Clin Gastroenterol Hepatol. 2019;17(6):1073-80.e1. DOI:10.1016/j.cgh.2018.06.018
60. Savarino E, Zentilin P, Mastracci L, et al. Microscopic esophagitis distinguishes patients with non-erosive reflux disease from those with functional heartburn. J Gastroenterol. 2013;48(4):473-82. DOI:10.1007/s00535-012-0672-2
61. Kandulski A, Weigt J, Caro C, et al. Esophageal intraluminal baseline impedance differentiates gastroesophageal reflux disease from functional heartburn. Clin Gastroenterol Hepatol. 2015;13(6):1075-81. DOI:10.1016/j.cgh.2014.11.033
62. Frazzoni M, de Bortoli N, Frazzoni L, et al. Impairment of chemical clearance and mucosal integrity distinguishes hypersensitive esophagus from functional heartburn. J Gastroenterol. 2017;52(4):444-51. DOI:10.1007/s00535-016-1226-9
63. Katzka DA, Pandolfino JE, Kahrilas PJ. Phenotypes of Gastroesophageal Reflux Disease: Wh ere Rome, Lyon, and Montreal Meet. Clin Gastroenterol Hepatol. 2020;18(4):767-76. DOI:10.1016/j.cgh.2019.07.015

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1. Drossman DA Functional gastrointestinal disorders: history, pathophysiology, clinical features and Rome IV. Gastroenterology. 2016;150:1262-79. DOI:10.1053/j.gastro.2016.02.032.0.1053/j.gastro.2016.02.032
2. Маев И.В., Бусарова Г.А., Андреев Д.Н. Болезни пищевода. М.: ГЭОТАР-Медиа, 2019 [Maev IV, Busarova GA, Andreev DN. Bolezni pishchevoda. Moscow: GEOTAR-Media, 2019 (in Russian)].
3. Zheng Z, Shang Y, Wang N, et al. Current Advancement on the Dynamic Mechanism of Gastroesophageal Reflux Disease. Int J Biol Sci. 2021;17(15):4154-64. DOI:10.7150/ijbs.65066
4. Isakov VA, Morozov SV, Stavraki ES, et al. Analiz rasprostranennosti izzhogi: natsional'noe epidemiologicheskoe issledovanie vzroslogo gorodskogo naseleniia (ARIADNA). Eksperimental'naia i klinicheskaia gastroenterologiia. 2008;1:20-30 (in Russian).
5. Ivashkin VT, Maev IV, Trukhmanov AS, 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 Russian). DOI:10.22416/1382-4376-2020-30-4-70-97
6. Ribolsi M, Giordano A, Guarino MPL, et al. New classifications of gastroesophageal reflux disease: an improvement for patient management? Expert Rev. Gastroenterol Hepatol. 2019;13(8):761-9. DOI:10.1080/17474124.2019.1645596
7. Savarino E, Zentilin P, Tutuian R, et al. The role of nonacid reflux in NERD: lessons learned fr om impedance-pH monitoring in 150 patients off therapy. Am J Gastroenterol. 2008;103(11):2685-93. DOI:10.1111/j.1572-0241.2008.02119.x
8. Savarino E, Tutuian R, Zentilin P, et al. Characteristics of reflux episodes and symptom association in patients with erosive esophagitis and nonerosive reflux disease: study using combined impedance-pH off therapy. Am J Gastroenterol. 2010;105(5):1053-61. DOI:10.1038/ajg.2009.670
9. Shinozaki S, Osawa H, Hayashi Y, et al. Long-term vonoprazan therapy is effective for controlling symptomatic proton pump inhibitor-resistant gastroesophageal reflux disease. Biomed Rep. 2021;14(3):32. DOI:10.3892/br.2021.1408
10. Lundell LR, Dent J, Bennett JR, et al. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut. 1999;45(2):172-80. DOI:10.1136/gut.45.2.172
11. Dent J, Becher A, Sung J, et al. Systematic review: patterns of reflux-induced symptoms and esophageal endoscopic findings in large-scale surveys. Clin Gastroenterol Hepatol. 2012;10(8):863-73.e3. DOI:10.1016/j.cgh.2012.02.028
12. Modlin IM, Hunt RH, Malfertheiner P, et al. Diagnosis and management of non-erosive reflux disease--the Vevey NERD Consensus Group. Digestion. 2009;80(2):74-88. DOI:10.1159/000219365
13. Patel A, Sayuk GS, Kushnir VM, et al. GERD phenotypes from pH-impedance monitoring predict symptomatic outcomes on prospective evaluation. Neurogastroenterol Motil. 2016;28(4):513-21. DOI:10.1111/nmo.12745
14. Gyawali CP, Kahrilas PJ, Savarino E, et al. Modern diagnosis of GERD: the Lyon Consensus. Gut. 2018;67(7):1351-62. DOI:10.1136/gutjnl-2017-314722
15. Yamasaki T, Fass R. Reflux Hypersensitivity: A New Functional Esophageal Disorder. J Neurogastroenterol Motil. 2017;23(4):495-503. DOI:10.5056/jnm17097
16. Fass R, Zerbib F, Gyawali CP. AGA Clinical Practice Update on Functional Heartburn: Expert Review. Gastroenterology. 2020;158(8):2286-93. DOI:10.1053/j.gastro.2020.01.034
17. Clouse RE, Richter JE, Heading RC, et al. Functional esophageal disorders. Gut. 1999;45 Suppl 2(Suppl. 2):II31-6. DOI:10.1136/gut.45.2008.ii31
18. Patel D, Fass R, Vaezi M. Untangling Nonerosive Reflux Disease From Functional Heartburn. Clin Gastroenterol Hepatol. 2021;19(7):1314-26. DOI:10.1016/j.cgh.2020.03.057
19. Quigley EM. Non-erosive reflux disease, functional heartburn and gastroesophageal reflux disease; insights into pathophysiology and clinical presentation. Chin J Dig Dis. 2006;7(4):186-90. DOI:10.1111/j.1443-9573.2006.00266.x
20. Savarino V, Marabotto E, Zentilin P, et al. Esophageal reflux hypersensitivity: Non-GERD or still GERD? Dig Liver Dis. 2020;52(12):1413-20. DOI:10.1016/j.dld.2020.10.003
21. Xu C, Niu X. Progress on the Mechanism of Visceral Hypersensitivity in Nonerosive Reflux Disease. Gastroenterol Res Pract. 2022;2022:4785077. DOI:10.1155/2022/4785077
22. Souza RF, Huo X, Mittal V, et al. Gastroesophageal reflux might cause esophagitis through a cytokine-mediated mechanism rather than caustic acid injury. Gastroenterology. 2009;137(5):1776-84. DOI:10.1053/j.gastro.2009.07.055
23. Kondo T, Oshima T, Tomita T, et al. Prostaglandin E(2) mediates acid-induced heartburn in healthy volunteers. Am J Physiol Gastrointest Liver Physiol. 2013;304(6):G568-73. DOI:10.1152/ajpgi.00276.2012
24. Sei H, Oshima T, Shan J, et al. Esophageal Epithelial-Derived IL-33 Is Upregulated in Patients with Heartburn. PLoS One. 2016;11(4):e0154234. DOI:10.1371/journal.pone.0154234
25. Shan J, Oshima T, Fukui H, et al. Acidic deoxycholic acid and chenodeoxycholic acid induce interleukin-8 production through p38 mitogen-activated protein kinase and protein kinase A in a squamous epithelial model. J Gastroenterol Hepatol. 2013;28(5):823-8. DOI:10.1111/jgh.12139
26. Simanenkov VI, Maev IV, Tkacheva ON, et al. Syndrome of increased epithelial permeability in clinical practice. Multidisciplinary national Consensus. Cardiovascular Therapy and Prevention. 2021;20(1):2758 (in Russian).
27. Kondo T, Miwa H. The Role of Esophageal Hypersensitivity in Functional Heartburn. J Clin Gastroenterol. 2017;51(7):571-8. DOI:10.1097/MCG.0000000000000885
28. Dickman R, Maradey-Romero C, Fass R. The role of pain modulators in esophageal disorders – no pain no gain. Neurogastroenterol Motil. 2014;26(5):603-10. DOI:10.1111/nmo.12339
29. Siwiec RM, Babaei A, Kern M, et al. Esophageal acid stimulation alters insular cortex functional connectivity in gastroesophageal reflux disease. Neurogastroenterol Motil. 2015;27(2):201-11. DOI:10.1111/nmo.12464
30. Wang P, Du C, Chen FX, et al. BDNF contributes to IBS-like colonic hypersensitivity via activating the enteroglia-nerve unit. Sci Rep. 2016;6:20320. DOI:10.1038/srep20320
31. Wouters MM, Vicario M, Santos J. The role of mast cells in functional GI disorders. Gut. 2016;65(1):155-68. DOI:10.1136/gutjnl-2015-309151
32. Xu X, Li Z, Zou D, et al. High expression of calcitonin gene-related peptide and substance P in esophageal mucosa of patients with non-erosive reflux disease. Dig Dis Sci. 2013;58(1):53-60. DOI:10.1007/s10620-012-2308-z
33. Wulamu W, Yisireyili M, Aili A, et al. Chronic stress augments esophageal inflammation, and alters the expression of transient receptor potential vanilloid 1 and protease-activated receptor 2 in a murine model. Mol Med Rep. 2019;19(6):5386-96. DOI:10.3892/mmr.2019.10192
34. Knowles CH, Aziz Q. Visceral hypersensitivity in non-erosive reflux disease. Gut. 2008;57(5):674-83. DOI:10.1136/gut.2007.127886
35. Silva RO, Bingana RD, Sales TMAL, et al. Role of TRPV1 receptor in inflammation and impairment of esophageal mucosal integrity in a murine model of nonerosive reflux disease. Neurogastroenterol Motil. 2018:e13340. DOI:10.1111/nmo.13340
36. Holzer P. Acid-sensing ion channels in gastrointestinal function. Neuropharmacology. 2015;94:72-9. DOI:10.1016/j.neuropharm.2014.12.009
37. Yan J, Edelmayer RM, Wei X, et al. Dural afferents express acid-sensing ion channels: a role for decreased meningeal pH in migraine headache. Pain. 2011;152(1):106-113. DOI:10.1016/j.pain.2010.09.036
38. Choi JM, Yang JI, Kang SJ, et al. Association Between Anxiety and Depression and Gastroesophageal Reflux Disease: Results From a Large Cross-sectional Study. J Neurogastroenterol Motil. 2018;24(4):593-602. DOI:10.5056/jnm18069
39. Chen X, Li P, Wang F, et al. Psychological Results of 438 Patients with persisting Gastroesophageal Reflux Disease Symptoms by Symptom Checklist 90-Revised Questionnaire. Euroasian J Hepatogastroenterol. 2017;7(2):117-21. DOI:10.5005/jp-journals-10018-1230
40. Rengarajan A, Pomarat M, Zerbib F, et al. Overlap of functional heartburn and reflux hypersensitivity with proven gastroesophageal reflux disease. Neurogastroenterol Motil. 2021;33(6):e14056. DOI:10.1111/nmo.14056
41. Broers C, Melchior C, Van Oudenhove L, et al. The effect of intravenous corticotropin-releasing hormone administration on esophageal sensitivity and motility in health. Am J Physiol Gastrointest Liver Physiol. 2017;312(5):G526-34. DOI:10.1152/ajpgi.00437.2016
42. Yamasaki T, Tomita T, Takimoto M, et al. Intravenous Corticotropin-releasing Hormone Administration Increases Esophageal Electrical Sensitivity in Healthy Individuals. J Neurogastroenterol Motil. 2017;23(4):526-32. DOI:10.5056/jnm17067
43. Broers C, Geeraerts A, Boecxstaens V, et al. The role of serotonin in the control of esophageal sensitivity assessed by multimodal stimulation in health. Neurogastroenterol Motil. 2021;33(3):e14057. DOI:10.1111/nmo.14057
44. Pourhamzeh M, Moravej FG, Arabi M, et al. The Roles of Serotonin in Neuropsychiatric Disorders. Cell Mol Neurobiol. 2022;42(6):1671-92. DOI:10.1007/s10571-021-01064-9
45. Lei WY, Chang WC, Wong MW, et al. Sleep Disturbance and Its Association with Gastrointestinal Symptoms/Diseases and Psychological Comorbidity. Digestion. 2019;99(3):205-12. DOI:10.1159/000490941
46. Xu J, Gao H, Zhang L, et al. Melatonin alleviates cognition impairment by antagonizing brain insulin resistance in aged rats fed a high-fat diet. J Pineal Res. 2019;67(2):e12584. DOI:10.1111/jpi.12584
47. Jiang H, Ling Z, Zhang Y, et al. Altered fecal microbiota composition in patients with major depressive disorder. Brain Behav Immun. 2015;48:186-94. DOI:10.1016/j.bbi.2015.03.016
48. Zheng P, Zeng B, Zhou C, et al. Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host's metabolism. Mol Psychiatry. 2016;21(6):786-96. DOI:10.1038/mp.2016.44
49. D'Souza SM, Houston K, Keenan L, et al. Role of microbial dysbiosis in the pathogenesis of esophageal mucosal disease: A paradigm shift from acid to bacteria? World J Gastroenterol. 2021;27(18):2054-72. DOI:10.3748/wjg.v27.i18.2054
50. Savarino E, Pohl D, Zentilin P, et al. Functional heartburn has more in common with functional dyspepsia than with non-erosive reflux disease. Gut. 2009;58(9):1185-91. DOI:10.1136/gut.2008.175810
51. Kushnir VM, Sathyamurthy A, Drapekin J, et al. Assessment of concordance of symptom reflux association tests in ambulatory pH monitoring. Aliment Pharmacol Ther. 2012;35:1080-7. DOI:10.1111/j.1365-2036.2012.05066.x
52. Maev IV, Barkalova EV, Ovsepyan MA, et al. Possibilities of pH impedance and high-resolution manometry in managing patients with refractory gastroesophageal reflux disease. Terapevticheskii Arkhiv (Ter. Arkh.). 2017;89(2):76-83 (in Russian).
53. Barkalova EV, Kucheryavyy YuA, Ovsepian MA, Maev IV. Heartburn in patients without esophagitis. Differential diagnosis. Experimental and clinical gastroenterology. 2018;158(10):74-9 (in Russian). DOI:10.31146/1682-8658-ecg-158-10-74-79
54. Savarino E, Gemignani L, Pohl D, et al. Oesophageal motility and bolus transit abnormalities increase in parallel with the severity of gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2011;34:476-86. DOI:10.1111/j.1365-2036.2011.04742.x
55. Maev IV, Samsonov AA, Andreev DN. Klinicheskoe znachenie sindroma "perekresta" funktsional'noi dispepsii i gastroezofageal'noi refliuksnoi bolezni. Klinicheskie perspektivy gastroenterologii, gepatologii. 2013;5:17-22 (in Russian).
56. Maev IV, Andreev DN, Dicheva DT, et al. Funktsional'naia dispepsiia: sovremennoe sostoianie problemy. Meditsinskii vestnik MVD. 2013;4:38-45 (in Russian).
57. Maev IV, Dicheva DT, Andreev DN. Podkhody k individualizatsii lecheniia gastroezofageal'noi refliuksnoi bolezni. Effektivnaia farmakoterapiia. Gastroenterologiia. 2012;4:18-22 (in Russian).
58. Mayev IV, Samsonov AA, Andreev DN, Kochetov SA. Differentiated treatment of functional dyspepsia syndrome. Meditsinskii sovet. 2012;9:13-20 (in Russian).
59. Abdallah J, George N, Yamasaki T, et al. Most Patients With Gastroesophageal Reflux Disease Who Failed Proton Pump Inhibitor Therapy Also Have Functional Esophageal Disorders. Clin Gastroenterol Hepatol. 2019;17(6):1073-80.e1. DOI:10.1016/j.cgh.2018.06.018
60. Savarino E, Zentilin P, Mastracci L, et al. Microscopic esophagitis distinguishes patients with non-erosive reflux disease from those with functional heartburn. J Gastroenterol. 2013;48(4):473-82. DOI:10.1007/s00535-012-0672-2
61. Kandulski A, Weigt J, Caro C, et al. Esophageal intraluminal baseline impedance differentiates gastroesophageal reflux disease from functional heartburn. Clin Gastroenterol Hepatol. 2015;13(6):1075-81. DOI:10.1016/j.cgh.2014.11.033
62. Frazzoni M, de Bortoli N, Frazzoni L, et al. Impairment of chemical clearance and mucosal integrity distinguishes hypersensitive esophagus from functional heartburn. J Gastroenterol. 2017;52(4):444-51. DOI:10.1007/s00535-016-1226-9
63. Katzka DA, Pandolfino JE, Kahrilas PJ. Phenotypes of Gastroesophageal Reflux Disease: Wh ere Rome, Lyon, and Montreal Meet. Clin Gastroenterol Hepatol. 2020;18(4):767-76. DOI:10.1016/j.cgh.2019.07.015

И.В. Маев, Е.В. Баркалова, М.А. Овсепян, Д.Н. Андреев*

ФГБОУ ВО «Московский государственный медико-стоматологический университет им. А.И. Евдокимова» Минздрава России, Москва, Россия
*dna-mit8@mail.ru

________________________________________________

Igor V. Maev, Elena V. Barkalova, Mariia A. Ovsepian, Dmitry N. Andreev*

Yevdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia
*dna-mit8@mail.ru