Проблемы ноцицепции при гастроэзофагеальной рефлюксной болезни: диагностика и лечение раздраженного пищевода

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Аннотация

В статье рассматриваются такие факторы патогенеза симптомов при гастроэзофагеальной рефлюксной болезни (ГЭРБ), как активация ноцицепторов, гиперэкспрессия провоспалительных цитокинов и повышение функциональной активности иммунокомпетентных клеток. Приведена современная классификация ГЭРБ, основанная на выделении четырех фенотипов заболевания по диагностическим критериям и прогнозу эффективности лечения. Показана значимость рН-импедансометрии пищевода для диагностики фенотипов ГЭРБ по выраженности рефлюкса и связи симптомов с рефлюксом. Представлены диагностические критерии функциональной изжоги и гиперсенситивного пищевода согласно Римским критериям IV пересмотра (2016). Приведены данные собственных исследований, согласно которым раздраженный пищевод наблюдался у 26,2% здоровых лиц и у 24,2% больных ГЭРБ с эндоскопическими или рН-метрическими проявлениями заболевания. Подчеркнута роль нарушения клиренса пищевода в патогенезе ГЭРБ. Приводится обзор современных данных литературы об эффективности хирургического лечения у пациентов с различными фенотипами ГЭРБ, а также оценка клинической эффективности длительного применения ингибиторов протонной помпы. Обсуждаются преимущества антисекреторного препарата последнего поколения рабепразола у разных категорий больных и возможности его применения при различных формах ГЭРБ.

Ключевые слова: течение, прогноз эффективности лечения гастроэзофагеальной рефлюксной болезни, гиперсенситивный, раздраженный пищевод, функциональная изжога, pH-импедансометрия, ингибиторы протонной помпы, рабепразол.

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The following factors of gastroesophageal reflux disease (GERD) pathogenesis are addressed in the abstract: activation of nociceptors, hyperexpression of pro-inflammatory cytokines and increase of functional activity of immune competent cells. The current classification of GERD is given which is based on identification of 4 phenotypes of the disease according to diagnostic criteria and prognosis of treatment effectiveness. Importance of pH-impedance monitoring in GERD diagnostics is demonstrated based on its primary significance for identification of reflux nature and determination of relationship between GERD symptoms and reflux. The diagnostics criteria of functional heartburn and hypersensitive oesophagus according to Rome IV criteria (2016) are presented. The data of the private investigation are demonstrated according to which irritated oesophagus was observed in 26.2% of healthy persons and in 24.2% of GERD patients with endoscopic or pH-metric symptoms of the disease. Implication of oesophagus clearance disorder in GERD pathogenesis has been pointed out. An overview of the current literature data about effectiveness of surgical treatment in patients with different GERD phenotypes and also assessment of clinical effectiveness of long-term treatment with PPI are given. Advantages of anti-secretory drug of the last generation rabeprazole in different patient groups and possibilities of its use in all GERD phenotypes have been discussed.

Keywords: course of gastroesophageal reflux disease, prognosis of treatment effectiveness, hypersensitive, irritable oesophagus, functional heartburn, pH-impedance monitoring, proton pump inhibitors, rabeprazole.

Список литературы

1. Bredenoord AJ. Mechanisms of reflux perception in gastroesophageal reflux disease: a review. Am J Gastroenterol. 2012;107:8-15.
2. Sifrim D, Fornari F. Esophageal impedance-pH monitoring. Dig Liver Dis. 2008;40:161-166.
3. Villa N, Vela MF. Impedance-pH testing. Gastroenterol Clin N Am. 2013;42:17-26.
4. Saleh CMG, Smout JPM, Bredenoord AJ. The diagnosis of gastro-esophageal reflux disease cannot be made with barium esophagograms. Neurogastroenterol Motil. 2015;27:195-200.
5. Namiot Z, Sarosiek J, Marcinkiewicz M, et al. Declined human esophageal mucin secretion in patients with severe reflux esophagitis. Dig Dis Sci. 1994;39:2523-2529.
6. Niv Y, Fass R. The role of mucin in GERD and its complications. Gastroenterol Hepatol. 2011;9(1):55-59.
7. Van Roon AHC, Mayne GC, Wijnhoven BPL, et al. Impact of gastro-esophageal reflux on mucin mRNA expression in the esophageal mucosa. J Gastrointest Surg. 2008;12:1331-1340.
8. Emerenziani S, Sifrim D, Habib FJ, et al. Presence of gas in the refluxate enhances reflux perception in non-erosive patients with physiological acid exposure of the oesophagus. Gut. 2008;57:443-447.
9. Aziz Q, Fass R, Gyawali CP, et al. Functional Esophageal Disorders. Gastroenterology. 2016;150:1368-1379.
10. Altomare A, Guarino M, Cicala M, et al. Gastrointestinal sensitivity and gastrointestinal reflux disease. Ann NY Acad Sci. 2013;1300:80-95.
11. Sugiura T, Tominaga M, Katsuya H, Mizumura K. Bradykinin low-ered the threshold temperature for heat activation of vanilloid receptor. J Neurophysiol. 2002;88:544-548.
12. Rosenbaum T, Gordon-Shaag A, Munari M., Gordon SE. Ca2+ /calmodulin modulates TRPV1 activation by capsaicin. J Gen Physiol. 2004;123:53-62.
13. Shaheen NJ, Falk GW, Iyer PG, et al. ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus. Am J Gastroenterol. 2016;111(1):30-50.
14. Boeckxstaens G, El-Serag H. Republished: Symptomatic reflux disease: the present, the past and the future. Postgrad Med J. 2015;91:46-54.
15. Саблин О.А. Гастроэзофагеальная рефлюксная болезнь и ее внепищеводные проявления: современные представления о диагностике и лечении. Автореф. дис. … докт. мед. наук. Санкт-Петербург; 2004. 45 с. [Sablin OA. Gastroezofageal’naya reflyuksnaya bolezn’ i ee vnepishchevodnye proyavleniya: sovremennye predstavleniya o diagnostike i lechenii. Avtoref. dis. … dokt. med. nauk [Gastro-esophageal reflux disease and its extra-oesophageal manifestations: clinical and diagnostic significance of motor dysfunctions of the upper digestive tract: Authors abstract of Diss. ... Doct. Med. Sci.]. Sankt-Peterburg; 2004. 45 p. (In Russ.)].
16. Patel A, Sayuk GS, Kushnir VM, Chan WW, Gyawali CP. GERD phenotypes from pH-impedance monitoring predict symptomatic outcomes on prospective evaluation. Neurogastroenterol Motil. 2016;28(4):513-521.
17. Dent J, Armstrong D, Delaney B, Moayyedi P, Talley NJ, Vakil N. Symptom evaluation in reflux disease: workshop background, processes, terminology, recommendations, and discussion outputs. Gut. 2004;53 Suppl. 4:1-24.
18. Kirchheiner J, Glatt S, Fuhr U, Klotz U, et al. Relative potency of proton-pump inhibitors—comparison of effects on intragastric pH. Eur J Clin Pharmacol. 2009;65(1):19-31.
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20. Маев И.В., Трухманов А.С., Кучерявый Ю.А. Фармакоэкономика кислотозависимых заболеваний. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2006;(3):68-76 [Maev IV, Trukhmanov AS, Kucheryavyy YuA. Pharmacoeconomics of acid-dependent diseases. Rossiyskiy Zhurnal Gastroenterologii, Gepatologii, Koloproktologii. 2006;(3):68-76 (In Russ.)].
21. Barnett JL, Robinson M. Optimizing acid-suppression therapy. Manag Care. 2001;10(10):17-21.
22. Samer CF, Lorenzini K, Rollason V, et al., Applications of CYP450 Testing in the Clinical Setting. Mol Diagn Ther. 2013;17:165-184.
23. Ichikawa H, Sugimoto M, Sugimoto K, et al. Rapid metabolizer genotype of CYP2C19 is a risk factor of being refractory to proton pump inhibitor therapy for reflux esophagitis. J Gastroenterol Hepatol. 2016;31(4):716-726.
24. Ивашкин В.Т., Маев И.В., Трухманов А.С. и др. Клинические рекомендации Российской гастроэнтерологической ассоциации по диагностике и лечению гастроэзофагеальной рефлюксной болезни. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2017;27(4):75-95 [Ivashkin VT, Maev IV, Trukhmanov AS,
et al. Clinical recommendations of the Russian gastroenterological association for the diagnosis and treatment of gastroesophageal reflux disease. Rossiyskiy Zhurnal Gastroenterologii, Gepatologii, Koloproktologii. 2017;27(4):75-95 (In Russ.)].
25. Barrison AF, Jarbe LA, Weinberg MD, et al. Patterns of proton pump inhibitors in clinical practice. Am J Med. 2001;111:469-473.
26. Gunaratnam NT, Jessup TP, Inadomi J. Sub-optimal proton pump inhibitor dosing is prevalent in patients with poorly controlled gastrooesophageal reflux disease. Aliment Pharmacol Ther. 2006;23: 1473-7.
27. Pezanoski J, Guanaratnam N, Cowen M. Correct and incorrect dosing of proton pump inhibitors and its impact on GERD symptoms. Gastroenterology. 2003;124 Suppl.:128.
28. Kinoshita Y, Ashida K, Hongo M. Randomised clinical trial: a multicentre, double-blind, placebo-controlled study on the efficacy and safety of rabeprazole 5 mg or 10 mg once daily in patients with non-erosive reflux disease. Aliment Pharmacol Ther. 2011;33(2):213-224.
29. Sarosiek I, Olyaee M, Majewski M, et al. Significant Increase of Esophageal Mucin Secretion in Patients with Reflux Esophagitis After Healing with Rabeprazole: Its Esophagoprotective Potential. Dig Dis Sci. 2009;54(10):2137-2142.

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1. Bredenoord AJ. Mechanisms of reflux perception in gastroesophageal reflux disease: a review. Am J Gastroenterol. 2012;107:8-15.
2. Sifrim D, Fornari F. Esophageal impedance-pH monitoring. Dig Liver Dis. 2008;40:161-166.
3. Villa N, Vela MF. Impedance-pH testing. Gastroenterol Clin N Am. 2013;42:17-26.
4. Saleh CMG, Smout JPM, Bredenoord AJ. The diagnosis of gastro-esophageal reflux disease cannot be made with barium esophagograms. Neurogastroenterol Motil. 2015;27:195-200.
5. Namiot Z, Sarosiek J, Marcinkiewicz M, et al. Declined human esophageal mucin secretion in patients with severe reflux esophagitis. Dig Dis Sci. 1994;39:2523-2529.
6. Niv Y, Fass R. The role of mucin in GERD and its complications. Gastroenterol Hepatol. 2011;9(1):55-59.
7. Van Roon AHC, Mayne GC, Wijnhoven BPL, et al. Impact of gastro-esophageal reflux on mucin mRNA expression in the esophageal mucosa. J Gastrointest Surg. 2008;12:1331-1340.
8. Emerenziani S, Sifrim D, Habib FJ, et al. Presence of gas in the refluxate enhances reflux perception in non-erosive patients with physiological acid exposure of the oesophagus. Gut. 2008;57:443-447.
9. Aziz Q, Fass R, Gyawali CP, et al. Functional Esophageal Disorders. Gastroenterology. 2016;150:1368-1379.
10. Altomare A, Guarino M, Cicala M, et al. Gastrointestinal sensitivity and gastrointestinal reflux disease. Ann NY Acad Sci. 2013;1300:80-95.
11. Sugiura T, Tominaga M, Katsuya H, Mizumura K. Bradykinin low-ered the threshold temperature for heat activation of vanilloid receptor. J Neurophysiol. 2002;88:544-548.
12. Rosenbaum T, Gordon-Shaag A, Munari M., Gordon SE. Ca2+ /calmodulin modulates TRPV1 activation by capsaicin. J Gen Physiol. 2004;123:53-62.
13. Shaheen NJ, Falk GW, Iyer PG, et al. ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus. Am J Gastroenterol. 2016;111(1):30-50.
14. Boeckxstaens G, El-Serag H. Republished: Symptomatic reflux disease: the present, the past and the future. Postgrad Med J. 2015;91:46-54.
15. Саблин О.А. Гастроэзофагеальная рефлюксная болезнь и ее внепищеводные проявления: современные представления о диагностике и лечении. Автореф. дис. … докт. мед. наук. Санкт-Петербург; 2004. 45 с. [Sablin OA. Gastroezofageal’naya reflyuksnaya bolezn’ i ee vnepishchevodnye proyavleniya: sovremennye predstavleniya o diagnostike i lechenii. Avtoref. dis. … dokt. med. nauk [Gastro-esophageal reflux disease and its extra-oesophageal manifestations: clinical and diagnostic significance of motor dysfunctions of the upper digestive tract: Authors abstract of Diss. ... Doct. Med. Sci.]. Sankt-Peterburg; 2004. 45 p. (In Russ.)].
16. Patel A, Sayuk GS, Kushnir VM, Chan WW, Gyawali CP. GERD phenotypes from pH-impedance monitoring predict symptomatic outcomes on prospective evaluation. Neurogastroenterol Motil. 2016;28(4):513-521.
17. Dent J, Armstrong D, Delaney B, Moayyedi P, Talley NJ, Vakil N. Symptom evaluation in reflux disease: workshop background, processes, terminology, recommendations, and discussion outputs. Gut. 2004;53 Suppl. 4:1-24.
18. Kirchheiner J, Glatt S, Fuhr U, Klotz U, et al. Relative potency of proton-pump inhibitors—comparison of effects on intragastric pH. Eur J Clin Pharmacol. 2009;65(1):19-31.
19. Di Mario F, Panozzo MP, Baldassarre G, et al. The branded proton pump inhibitors (PPIs) increase levels of gastrin 17 (G-17) more than the generic ones in dyspeptic patients from an italian primary care population. Abstracts of the 23rd National Congress of Digestive Diseases. Dig Liver Dis. 2017;49S2:e73-e223.
20. Маев И.В., Трухманов А.С., Кучерявый Ю.А. Фармакоэкономика кислотозависимых заболеваний. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2006;(3):68-76 [Maev IV, Trukhmanov AS, Kucheryavyy YuA. Pharmacoeconomics of acid-dependent diseases. Rossiyskiy Zhurnal Gastroenterologii, Gepatologii, Koloproktologii. 2006;(3):68-76 (In Russ.)].
21. Barnett JL, Robinson M. Optimizing acid-suppression therapy. Manag Care. 2001;10(10):17-21.
22. Samer CF, Lorenzini K, Rollason V, et al., Applications of CYP450 Testing in the Clinical Setting. Mol Diagn Ther. 2013;17:165-184.
23. Ichikawa H, Sugimoto M, Sugimoto K, et al. Rapid metabolizer genotype of CYP2C19 is a risk factor of being refractory to proton pump inhibitor therapy for reflux esophagitis. J Gastroenterol Hepatol. 2016;31(4):716-726.
24. [Ivashkin VT, Maev IV, Trukhmanov AS,
et al. Clinical recommendations of the Russian gastroenterological association for the diagnosis and treatment of gastroesophageal reflux disease. Rossiyskiy Zhurnal Gastroenterologii, Gepatologii, Koloproktologii. 2017;27(4):75-95 (In Russ.)].
25. Barrison AF, Jarbe LA, Weinberg MD, et al. Patterns of proton pump inhibitors in clinical practice. Am J Med. 2001;111:469-473.
26. Gunaratnam NT, Jessup TP, Inadomi J. Sub-optimal proton pump inhibitor dosing is prevalent in patients with poorly controlled gastrooesophageal reflux disease. Aliment Pharmacol Ther. 2006;23: 1473-7.
27. Pezanoski J, Guanaratnam N, Cowen M. Correct and incorrect dosing of proton pump inhibitors and its impact on GERD symptoms. Gastroenterology. 2003;124 Suppl.:128.
28. Kinoshita Y, Ashida K, Hongo M. Randomised clinical trial: a multicentre, double-blind, placebo-controlled study on the efficacy and safety of rabeprazole 5 mg or 10 mg once daily in patients with non-erosive reflux disease. Aliment Pharmacol Ther. 2011;33(2):213-224.
29. Sarosiek I, Olyaee M, Majewski M, et al. Significant Increase of Esophageal Mucin Secretion in Patients with Reflux Esophagitis After Healing with Rabeprazole: Its Esophagoprotective Potential. Dig Dis Sci. 2009;54(10):2137-2142.

Авторы

O.A. Sablin 1, T.A. Ilchishina 2

1 А.М. Nikiforov Russian Center of Emergency and Radiation Medicine, Ministry of Russian Federation for Civil Defense, Emergencies and Elimination of Consequences of Natural Disasters, Saint-Petersburg, Russia;
2 SM-clinic, Saint-Petersburg, Russia

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