Laryngopharyngeal reflux: current perspectives and controversies
DOI:
https://doi.org/10.14739/mmt.2025.3.335612Keywords:
laryngopharyngeal reflux, gastroesophageal reflux dіsease, аutonomic nervous system, vagal reflex, physiological сardia incompetence, esophageal motility disorders, achalasiaAbstract
The aim of this study is to systematize current concepts and describe key pathogenetic variants of laryngopharyngeal reflux formation based on the analysis of recent experimental research and clinical observations.
Materials and methods. The study examined pathogenetic mechanisms of laryngopharyngeal reflux (LPR) formation using methods of analysis, synthesis, and generalization of scientific data. The information base was formed through a systematic literature search in international scientometric databases, in particular PubMed, Scopus, Web of Science, and Google Scholar. A total of 90 sources were selected for further analysis according to criteria of scientific significance (high journal quartile, authors’ h-index, and statistical validity). The search strategy included the identification of the topic’s relevance, formulation of appropriate queries (laryngopharyngeal reflux, vagus reflex, autonomic nervous system, etc.), critically assessing the reliability of sources, comparing results between studies, and summarizing the data obtained.
Results. The literature review revealed that LPR is a multifactorial, complex, and poorly standardized syndrome with a wide range of nonspecific symptoms. Theoretical analysis identified four principal pathogenetic mechanisms of LPR: chemical (microaspiration and mucosal damage), neuro-reflex (hypersensitivity), muscular (laryngeal overload), and immunobiological (chronic inflammation and microbiota imbalance). LPR may result from esophageal motility disorders, sphincter dysfunction, neuroimmune and psychovegetative disturbances while its chronicity is promoted by central and peripheral sensitization, stress, genetic predisposition, and behavioral factors including obesity, smoking, diet, and medication. It was established that there is no universal diagnostic standard for LPR, and current diagnostic approaches remain complex and fragmented, relying largely on the exclusion of other pathologies and empirical treatment.
Conclusions. The complex and heterogeneous pathogenesis of laryngopharyngeal reflux accounts for its symptoms variability. Identification of distinct pathogenetic variants or typical phenotypes with specific clusters of morphological, structural, functional, biochemical, instrumental, and psychometric features will facilitate the development of highly effective integrative pharmacological treatment approaches.
References
Mishra P, Agrawal D, Chauhan K, Kaushik M. Prevalence of Laryngopharyngeal Reflux Disease in Indian Population. Indian J Otolaryngol Head Neck Surg. 2022;74(Suppl 2):1877-81. doi: https://doi.org/10.1007/s12070-020-01882-1
Li CF, Zhang LH, Wang WL, Cao J, Wang YG, Zhao YX. [The prevalence and relationship between laryngopharyngeal reflux disease, anxiety and depression in otolaryngology outpatients]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2020;55(3):241-8. Chinese. doi: https://doi.org/10.3760/cma.j.issn.1673-0860.2020.03.010
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. doi: https://doi.org/10.1007/s12070-020-01882-110.1002/lary.31134
Yadlapati R, Kaizer AM, Sikavi DR, Greytak M, Cai JX, Carroll TL, et al. Distinct Clinical Physiologic Phenotypes of Patients With Laryngeal Symptoms Referred for Reflux Evaluation. Clin Gastroenterol Hepatol. 2022;20(4):776-86.e1. doi: https://doi.org/10.1016/j.cgh.2021.05.025
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. doi: https://doi.org/10.1177/0194599819827488
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):141-5. doi: https://doi.org/10.21053/ceo.2017.00577
Wu Y, Wang J, Huang Q, Peng T, Zhao L, Feng G, et al. The Relationship Between Gastroesophageal Reflux Disease and Laryngopharyngeal Reflux Based on pH Monitoring. Ear Nose Throat J. 2021;100(4):249-53. doi: https://doi.org/10.1177/0145561320971915
Jing W, Luo W, Lou L. Diagnostic utility of salivary pepsin in laryngopharyngeal reflux: a systematic review and meta-analysis. Braz J Otorhinolaryngol. 2023;89(2):339-47. doi: https://doi.org/10.1016/j.bjorl.2022.10.050
Lien HC, Wang CC, Kao JY, Yeh HZ, Hsu JY, Lee SW, et al. Distinct physiological characteristics of isolated laryngopharyngeal reflux symptoms. Clin Gastroenterol Hepatol. 2020;18(7):1466-74.e4. doi: https://doi.org/10.1016/j.cgh.2019.08.064
Shilpa C, Sandeep S, Chandresh S, Grampurohit A, Shetty TS. Laryngopharyngeal reflux and GERD: correlation between reflux symptom index and reflux finding score. Indian J Otolaryngol Head Neck Surg. 2019;71(Suppl 1):684-8. doi: https://doi.org/10.1007/s12070-018-1480-7
Liu CP, Jiang AY, Chen F, Wu J, Wang SY, Cao L, et al. Predictive value of laryngeal mucosa pepsin in therapeutic response of laryngopharyngeal reflux. J Voice. 2024;38(6):1412-8. doi: https://doi.org/10.1016/j.jvoice.2022.05.013
Lechien JR, Bobin F. Variability and accuracy of multiple saliva pepsin measurements in laryngopharyngeal reflux patients. J Otolaryngol Head Neck Surg. 2023;52(1):66. doi: https://doi.org/10.1186/s40463-023-00670-5
Carroll TL, Werner A, Nahikian K, Dezube A, Roth DF. Rethinking the laryngopharyngeal reflux treatment algorithm: evaluating an alternate empiric dosing regimen and considering up-front, pH-impedance, and manometry testing to minimize cost in treating suspect laryngopharyngeal reflux disease. Laryngoscope. 2017;127(Suppl 6):S1-13. doi: https://doi.org/10.1002/lary.26806
Duricek M, Banovcin P Jr, Halickova T, Hyrdel R, Kollarik M. Comprehensive analysis of acidic pharyngeal reflux before and after proton pump inhibitor treatment in patients with suspected laryngopharyngeal reflux. Eur J Gastroenterol Hepatol. 2020;32(2):166-74. doi: https://doi.org/10.1097/MEG.0000000000001584
O’Hara J, Stocken DD, Watson GC, Fouweather T, McGlashan J, MacKenzie K, et al. Use of proton pump inhibitors to treat persistent throat symptoms: multicentre, double blind, randomised, placebo controlled trial. BMJ. 2021;372:m4903. doi: https://doi.org/10.1136/bmj.m4903
Tseng WH, Hsu WC, Yang TL, Hsiao TY, Wu JF, Lee HC, et al. Proton Pump Inhibitor-unresponsive Laryngeal Symptoms Are Associated With Psychological Comorbidities and Sleep Disturbance: A Manometry and Impedance-pH Monitoring Study. J Neurogastroenterol Motil. 2023;29(3):314-25. doi: https://doi.org/10.5056/jnm22099
Liu K, Krause A, Yadlapati R. Quality of Life and Laryngopharyngeal Reflux. Dig Dis Sci. 2023;68(9):3527-33. doi: https://doi.org/10.1007/s10620-023-08027-8
Yadlapati R, Kaizer AM, Sikavi DR, Greytak M, Cai JX, Carroll TL, et. al. Distinct Clinical Physiologic Phenotypes of Patients With Laryngeal Symptoms Referred for Reflux Evaluation. Clin Gastroenterol Hepatol. 2022;20(4):776-786.e1. doi: https://doi.org/10.1016/j.cgh.2021.05.025
Wang L, Wang G, Li L, Fan X, Liu H, Sun Z, et al. Relationship between laryngopharyngeal reflux disease and gastroesophageal reflux disease based on synchronous esophageal and oropharyngeal Dx-pH monitoring. Am J Otolaryngol. 2020;41(3):102441. doi: https://doi.org/10.1016/j.amjoto.2020.102441
Lechien JR, Bobin F, Muls V, Saussez S, Hans S. Laryngopharyngeal Reflux Disease is More Severe in Obese Patients: A Prospective Multicenter Study. Laryngoscope. 2021;131(11):E2742-8. doi: https://doi.org/10.1002/lary.29676
Krüger K, Holzinger F, Trauth J, Koch M, Heintze C, Gehrke-Beck S. Chronic cough. Dtsch Arztebl Int. 2022;119(5):59-65. doi: https://doi.org/10.3238/arztebl.m2021.0396
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):32-5. doi: https://doi.org/10.1067/mhn.2002.125760
Lechien JR, Saussez S, Mayo-Yanez M, Iannella G, Vaira LA. Reflux symptoms may develop in cases of throat mucosa injury, stress and related-autonomic nerve dysfunction. Am J Otolaryngol. 2023;44(1):103687. doi: https://doi.org/10.1016/j.amjoto.2022.103687
Kuzy J, Marshall C, Ranjbar PA, Alnouri G, Omari AA, Sethi HK, et al. Characterization of Laryngopharyngeal Reflux in the Elderly Population. J Voice. 2024:S0892-1997(23)00366-1. doi: https://doi.org/10.1016/j.jvoice.2023.11.005
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):141-5. doi: https://doi.org/10.21053/ceo.2017.00577
Kikuchi A, Kawamoto R, Mizumoto J, Akase T, Ninomiya D, Kumagi T. A case of laryngopharyngeal reflux-associated chronic cough: misinterpretation of treatment efficacy causes diagnostic delay. J Gen Fam Med. 2020;21(6):258-60. doi: https://doi.org/10.1002/jgf2.348
Lechien JR, Bobin F, Muls V, Horoi M, Thill MP, Dequanter D, et al. Patients with acid, high-fat and low-protein diet have higher laryngopharyngeal reflux episodes at the impedance-pH monitoring. Eur Arch Otorhinolaryngol. 2020;277(2):511-20. doi: https://doi.org/10.1007/s00405-019-05711-2
Li Y, Xu G, Zhou B, Tang Y, Liu X, Wu Y, et al. Effects of acids, pepsin, bile acids, and trypsin on laryngopharyngeal reflux diseases: physiopathology and therapeutic targets. Eur Arch Otorrinolaringol. 2022;279(6):2743-52. doi: https://doi.org/10.1007/s00405-021-07201-w
Kowalik K, Krzeski A. The role of pepsin in the laryngopharyngeal reflux. Otolaryngol Pol. 2017;71(6):7-13. doi: https://doi.org/10.5604/01.3001.0010.7194
Doukas PG, Vageli DP, Sasaki CT, Judson BL. Pepsin promotes activation of epidermal growth factor receptor and downstream oncogenic pathways, at slightly acidic and neutral pH, in exposed hypopharyngeal cells. Int J Mol Sci. 2021;22(8):4275. doi: https://doi.org/10.3390/ijms22084275
Yin CY, Zhang SS, Zhong JT, Zhou SH. Pepsin and laryngeal and hypopharyngeal carcinomas. Clin Exp Otorhinolaryngol. 2021;14(2):159-68. doi: https://doi.org/10.21053/ceo.2020.00465
Samuels TL, Blaine-Sauer S, Yan K, Plehhova K, Coyle C, Johnston N. Topical alginate protection against pepsin-mediated esophageal damage: E-cadherin proteolysis and matrix metalloproteinase induction. Int J Mol Sci. 2023;24(9):7932. doi: https://doi.org/10.3390/ijms24097932
Zubčić Ž, Mendeš T, Včeva A, Mihalj H, Bogović V, Milanković SG. Presence of pepsin in laryngeal tissue and saliva in benign and malignant neoplasms. Biosci Rep. 2020;40(11):BSR20200216. doi: https://doi.org/10.1042/BSR20200216
Choi YS, Na HG, Bae CH, Song SY, Kim YD. Pepsin exposure in a non-acidic environment upregulates mucin 5AC (MUC5AC) expression via matrix metalloproteinase 9 (MMP9)/nuclear factor κB (NF-κB) in human airway epithelial cells. Int Forum Allergy Rhinol. 2021;11(5):894-901. doi: https://doi.org/10.1002/alr.22685
Im NR, Lee DY, Kim B, Kim J, Jung KY, Kim TH, Baek SK. Role of matrix metalloproteinases 7 in the pathogenesis of laryngopharyngeal reflux: Decreased E-cadherin in acid-exposed primary human pharyngeal epithelial cells. Int J Mol Sci. 2019;20(21):5276. doi: https://doi.org/10.3390/ijms20215276
Aldhahrani A, Powell J, Ladak S, Ali M, Ali S, Verdon B, Pearson J, Ward C. The potential role of bile acids in acquired laryngotracheal stenosis. Laryngoscope. 2018;128(9):2029-33. doi: https://doi.org/10.1002/lary.27105
Sasaki CT, Doukas SG, Costa J, Vageli DP. Biliary reflux as a causal factor in hypopharyngeal carcinoma: New clinical evidence and implications. Cancer. 2019;125(20):3554-65. doi: https://doi.org/10.1002/cncr.32369
Xiaopeng B, Tanaka Y, Ihara E, Hirano K, Nakano K, Hirano M, Oda Y, Nakamura K. Trypsin induces biphasic muscle contraction and relaxation via transient receptor potential vanilloid 1 and neurokinin receptors 1/2 in porcine esophageal body. Eur J Pharmacol. 2017;797:65-74. doi: https://doi.org/10.1016/j.ejphar.2017.01.004
Bai X, Tanaka Y, Ihara E, Hirano K, Nakano K, Hirano M, et al. Trypsin induces biphasic muscle contraction and relaxation via transient receptor potential vanilloid 1 and neurokinin receptors 1/2 in porcine esophageal body. Eur J Pharmacol. 2017;797:65-74. doi: https://doi.org/10.1016/j.ejphar.2017.01.004
Patel DA, Yadlapati R, Vaezi MF. Esophageal motility disorders: current approach to diagnostics and therapeutics. Gastroenterology. 2022;162(6):1617-34. doi: https://doi.org/10.1053/j.gastro.202
Goyal RK, Rattan S. Role of mechanoregulation in mast cell-mediated immune inflammation of the smooth muscle in the pathophysiology of esophageal motility disorders. Am J Physiol Gastrointest Liver Physiol. 2024;326(4):G398-G410. doi: https://doi.org/10.1152/ajpgi.00258.2023
Yadlapati R, Kahrilas PJ, Fox MR, Bredenoord AJ, Prakash Gyawali C, Roman S, et. al. Esophageal motility disorders on high-resolution manometry: Chicago classification version 4.0©. Neurogastroenterol Motil. 2021;33(1):e14058. doi: https://doi.org/10.1111/nmo.14058. Erratum in: Neurogastroenterol Motil. 2024;36(2):e14179. doi: https://doi.org/10.1111/nmo.14179
Savarino E, Bredenoord AJ, Fox M, Pandolfino JE, Roman S, Gyawali CP; International Working Group for Disorders of Gastrointestinal Motility and Function. Expert consensus document: Advances in the physiological assessment and diagnosis of GERD. Nat Rev Gastroenterol Hepatol. 2017;14(11):665-76. doi: https://doi.org/10.1038/nrgastro.2017.130
Katzka DA, Kahrilas PJ. Advances in the diagnosis and management of gastroesophageal reflux disease. Gastroenterology. 2020;158(5):1250-63. doi: https://doi.org/10.1053/j.gastro.2020.01.047
Wang AM, Zhang Z, Zhang YJ, Wu H, Zhang WD, Ye M, et al. Association between laryngopharyngeal reflux disease and autonomic nerve dysfunction. Eur Arch Otorhinolaryngol. 2019;276(8):2283-7. doi: https://doi.org/10.1007/s00405-019-05482-w
Hutauruk SM, Kasim RS, Yusuf I. Autonomic nerve dysfunction in patient with laryngopharyngeal reflux: the study of heart rate variability findings. Am J Otolaryngol Head Neck Surg. 2022;5(2):1175. doi: https://doi.org/10.1007/s00405-019-05482-w
Benjamin T, Zackria S, Lopez R, Richter J, Thota PN. Upper esophageal sphincter abnormalities and high-resolution esophageal manometry findings in patients with laryngopharyngeal reflux. Scand J Gastroenterol. 2017;52(7):816-21. doi: https://doi.org/10.1080/00365521.2017.1322139
Balouch B, Vaid A, Vontela S, Alnouri G, Sataloff RT. Anatomic and manometric abnormalities of the upper and lower esophageal sphincters in patients with reflux disease. J Voice. 2024;38(3):746-53. doi: https://doi.org/10.1016/j.jvoice.2021.11.008
Wang Z, Chen Y, Sun H, Xiong J, Zeng Y, Chen Y, et al. Laryngopharyngeal reflux disease: Updated examination of pathophysiology and management. World J Gastroenterol. 2024;30(16):2209-28. doi: https://doi.org/10.3748/wjg.v30.i16.2209
Phua SY, McGarvey LP, Ngu MC, Ing AJ. Patients with gastro-oesophageal reflux disease and cough have impaired laryngopharyngeal mechanosensitivity. Thorax. 2005;60:488-92. doi: https://doi.org/10.1136/thx.2004.026125
Healey CA, O’Hara K, Lødrup AB, Boesby S, Drewes AM, Krarup AL. Esophageal submucosal injection of capsaicin but not acid elicits chest pain: demonstrating the presence and function of TRPV1 receptors in human esophagus. Am J Physiol Gastrointest Liver Physiol. 2021;320(3):G350-6. doi: https://doi.org/10.1152/ajpgi.00438.2020
Smith JA, McGarvey LPA, Sher MR, Holt K, Birring SS. Efficacy and tolerability of gefapixant for treatment of refractory or unexplained chronic cough: dose–response meta-analysis of randomized clinical trials. JAMA. 2023;329(5):412-21. doi: https://doi.org/10.1001/jama.2023.0205
Ludlow CL. Laryngeal reflexes: physiology, technique, and clinical use. J Clin Neurophysiol. 2015;32(4):284-93. doi: https://doi.org/10.1097/WNP.0000000000000187
Bianchi BL, Song PC, Amin MR, Branski RC. Quantifying laryngopharyngeal reflux in singers: perceptual and oropharyngeal pH monitoring data. J Voice. 2017;31(4):496.e1-496.e6. doi: https://doi.org/10.1016/j.jvoice.2016.10.014
Jung DH, Park H. Is Gastroesophageal Reflux Disease and Achalasia Coincident or Not? J Neurogastroenterol Motil. 2017;23(1):5-8. doi: https://doi.org/10.5056/jnm16121
Yip JLK, Balasuriya GK, Spencer SJ, Hill-Yardin EL. The role of intestinal macrophages in gastrointestinal homeostasis: Heterogeneity and implications in disease. Cell Mol Gastroenterol Hepatol. 2021;12(5):1701-18. doi: https://doi.org/10.1016/j.jcmgh.2021.08.021
Joshi V, Strege PR, Farrugia G, Beyder A. Mechanotransduction in gastrointestinal smooth muscle cells: role of mechanosensitive ion channels. Am J Physiol Gastrointest Liver Physiol. 2021;320(5):G897-G906. doi: https://doi.org/10.1152/ajpgi.00481.2020
Lechien JR, Briganti G. Reflux Disease in Singers: A Systematic Review. J Voice. 2024:S0892-1997(24)00415-6. doi: https://doi.org/10.1016/j.jvoice.2024.11.032
Tan JJ, Dai YF, Wang F, Lv ZH, Huang LJ, Peng LY, et al. Pepsin-mediated inflammation in laryngopharyngeal reflux via the ROS/NLRP3/IL-1β signaling pathway. Cytokine. 2024;178:156568. doi: https://doi.org/10.1016/j.cyto.2024.156568
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. doi: https://doi.org/10.2147/JIR.S282809
Chen H, Wang H, Yang F, Wang M, Chen X. Distinct microbiota dysbiosis in patients with laryngopharynx reflux disease compared to healthy controls. Eur Arch Otorhinolaryngol. 2022;279(7):3569-79. doi: https://doi.org/10.1007/s00405-022-07327-5
Hrebeniuk LV. Improvement of the prevention and treatment of nasopharyngeal signs of gastroesophageal reflux disease in children [dissertation]. Zaporizhzhia: Zaporizhzhia State Medical University; 2021.
Drossman DA, Hasler WL. Rome IV-Functional GI Disorders: Disorders of Gut-Brain Interaction. Gastroenterology. 2016;150(6):1257-61. doi: https://doi.org/10.1053/j.gastro.2016.03.035
Duan H, Cai X, Luan Y, Yang S, Yang J, Dong H, et al. Regulation of the Autonomic Nervous System on Intestine. Front Physiol. 2021;12:700129. doi: https://doi.org/10.3389/fphys.2021.700129
Ali MK, Saha S, Milkova N, Liu L, Sharma K, Huizinga JD, Chen JH. Modulation of the autonomic nervous system by one session of spinal low-level laser therapy in patients with chronic colonic motility dysfunction. Front Neurosci. 2022;16:882602. doi: https://doi.org/10.3389/fnins.2022.882602
Wong MW, Liu TT, Yi CH, Lei WY, Hung JS, Cock C, Omari T, Gyawali CP, Liang SW, Lin L, Chen CL. Oesophageal hypervigilance and visceral anxiety relate to reflux symptom severity and psychological distress but not to acid reflux parameters. Aliment Pharmacol Ther. 2021;54(7):923-30. doi: https://doi.org/10.1111/apt.16561
Wu YP, Zhou JX, Wu HB, Wu DP, Qin LZ, Qin B, et al. Clinical characteristics and risk factors of esophageal reflux hypersensitivity: A multicenter study. World J Gastroenterol. 2025;31(17):105281. doi: https://doi.org/10.3748/wjg.v31.i17.105281
Jaggers RM, DiSabato DJ, Loman BR, Kontic D, Spencer KD, Allen JM, et al. Stressor-Induced Reduction in Cognitive Behavior is Associated with Impaired Colonic Mucus Layer Integrity and is Dependent Upon the LPS-Binding Protein Receptor CD14. J Inflamm Res. 2022;15:1617-35. doi: https://doi.org/10.2147/JIR.S332793
Gottfried-Blackmore A, Habtezion A, Nguyen L. Noninvasive vagal nerve stimulation for gastroenterology pain disorders. Pain Manag. 2021;11(1):89-96. doi: https://doi.org/10.2217/pmt-2020-0067
Page AJ, Li H. Meal-Sensing Signaling Pathways in Functional Dyspepsia. Front Syst Neurosci. 2018;12:10. doi: https://doi.org/10.3389/fnsys.2018.00010
Ustaoglu A, Woodland P. Esophageal afferent innervation and its role in gastro-esophageal reflux disease symptoms. Curr Opin Gastroenterol. 2021;37(4):372-7. doi: https://doi.org/10.1097/MOG.0000000000000749
Klein Wolterink RG, Wu GS, Chiu IM, Veiga-Fernandes H. Neuroimmune Interactions in Peripheral Organs. Annu Rev Neurosci. 2022;45:339-360. doi: https://doi.org/10.1146/annurev-neuro-111020-105359
Vanuytsel T, Bercik P, Boeckxstaens G. Understanding neuroimmune interactions in disorders of gut-brain interaction: from functional to immune-mediated disorders. Gut. 2023;72(4):787-98. doi: https://doi.org/10.1136/gutjnl-2020-320633
Fikree A, Byrne P. Management of functional gastrointestinal disorders. Clin Med. 2021;21(1):44-52. doi: https://doi.org/10.7861/clinmed.2020-0980
Lam C, Liu WF, Bel RD, Chan K, Miller L, Brown MC, et al. Polymorphisms of the FOXF1 and MHC locus genes in individuals undergoing esophageal acid reflux assessments. Dis Esophagus. 2017;30(2):1-7. doi: https://doi.org/10.1111/dote.12456
van Nistelrooij AM, van der Korput HA, Broer L, van Marion R, van Berge Henegouwen MI, van Noesel CJ, et al. Single nucleotide polymorphisms in CRTC1 and BARX1 are associated with esophageal adenocarcinoma. J Carcinog. 2015;14:5. doi: https://doi.org/10.4103/1477-3163.157441
Tai CC, Medwid S, Mclntosh K, Chande N, Kim RB, Gregor J. Impact of CYP2C19 metabolizer status on esophageal mucosal inflammation, acid exposure, and motility among patients on chronic proton-pump inhibitor therapy with refractory symptoms of gastroesophageal reflux disease. J Can Assoc Gastroenterol. 202410;7(3):238-45. doi: https://doi.org/10.1093/jcag/gwae005
Lechien JR, Huet K, Khalife M, Fourneau AF, Finck C, Delvaux V, et al. Gender differences in the presentation of dysphonia related to laryngopharyngeal reflux disease: a case-control study. Eur Arch Otorhinolaryngol. 2018;275(6):1513-24. doi: https://doi.org/10.1007/s00405-018-4951-2
Honda J, Iijima K, Asanuma K, Ara N, Shiroki T, Kondo Y, et al. Estrogen enhances esophageal barrier function by potentiating occludin expression. Dig Dis Sci. 2016;61(4):1028-38. doi: https://doi.org/10.1007/s10620-015-3980-6
Abu-Freha N, Gat R, Philip A, Yousef B, Ben Shoshan L, Yardeni D, et al. Indications and findings of upper endoscopies in males and females, are they the same or different? J Clin Med. 2021;10(8):1620. doi: https://doi.org/10.3390/jcm10081620
Mantegazza C, Mallardo S, Rossano M, Meneghin F, Ricci M, Rossi P, et al. Laryngeal signs and pH-multichannel intraluminal impedance in infants and children: The missing ring: LPR and MII-pH in children. Dig Liver Dis. 2020;52(9):1011-6. doi: https://doi.org/10.1016/j.dld.2020.05.001
Wang YG, Guo YH, Li CF, Zhu JL, Chi YY, Zhao YX, et al. [Investigation of laryngopharyngeal reflux prevalence and risk factors in otolaryngology]. J Clin Otorhinolaryngol Head Neck Surg. 2020;34(1):33-5. Chinese. doi: https://doi.org/10.13201/j.issn.1001-1781.2020.01.008
Liu Z, Zhang C, Wang X, Zhang J, Liu L, Wang J, et al. Characteristics of laryngopharyngeal reflux in patients of different genders and ages. J Voice. 2022:S0892-1997(22)00387-3. doi: https://doi.org/10.1016/j.jvoice.2022.11.035
Lakananurak N, Pitisuttithum P, Susantitaphong P, Patcharatrakul T, Gonlachanvit S. The efficacy of dietary interventions in patients with gastroesophageal reflux disease: A systematic review and meta-analysis of intervention studies. Nutrients. 2024;16(3):464. doi: https://doi.org/10.3390/nu16030464
Zhao YX, Zhang LH, Li CF, Wang WL, Wang YG. [Analysis of related factors of laryngopharyngeal reflux disease in teachers]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2022;57(7):874-9. Chinese. doi: https://doi.org/10.3760/cma.j.cn115330-20211104-00715
He J, Wang C, Li W. Laryngopharyngeal reflux in obstructive sleep apnea-hypopnea syndrome: an updated meta-analysis. Nat Sci Sleep. 2022;14:2189-201. doi: https://doi.org/10.2147/NSS.S390272
Yang XP, Xie Q, Xie J, Chen X. [Analysis of upper airway morphology and laryngopharyngeal reflux in obese patients with OSA]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2022;57(7):874-9. Chinese. doi: https://doi.org/10.3760/cma.j.cn115330-20211104-00715
Mitchell DR, Derakhshan MH, Wirz AA, Ballantyne SA, McColl KEL. Abdominal compression by waist belt aggravates gastroesophageal reflux, primarily by impairing esophageal clearance. Gastroenterology. 2017;152(8):1881-8. doi: https://doi.org/10.1053/j.gastro.2017.02.036
Le YT, Luu MN, Mai LH, Hoang AT, Nguyen TT, Quach DT. Prevalence and characteristics of gastroesophageal reflux disease in pregnant women. Rev Gastroenterol Mex (Engl Ed). 2023;88(4):341-6. doi: https://doi.org/10.1016/j.rgmxen.2022.06.012
Nykonenko AO, Haidarzhi YE, Kiosov OM. Endoscopic signs of gastroesophageal reflux disease with different hiatal hernias types. Pathologia. 2022;19(1):58-64. doi: https://doi.org/10.14739/2310-1237.2022.1.252191
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