Non-Acid GERC: Pathogenesis, Diagnosis and Management


Authors : Yadav Ambedkar Kumar; Li Yu; Xianghuai Xu; Yadav Abishek; Yadav Dhananjay

Volume/Issue : Volume 9 - 2024, Issue 5 - May

Google Scholar : https://tinyurl.com/4nmdczw7

Scribd : https://tinyurl.com/43smtfs8

DOI : https://doi.org/10.38124/ijisrt/IJISRT24MAY390

Abstract : Total Recent investigations have highlighted the pivotal influence of non-acid reflux in the etiology of chronic cough associated with gastroesophageal reflux disease (GERC). Differentiation between acid and non- acid GERC is effectively achieved through esophageal pH monitoring, with non-acid reflux drawing attention for its linkage to non-standard symptoms and the intricacies involved in its management. The combination of multi-channel intraluminal impedance with pH monitoring (MII-PH) and its related metrics, including acid exposure time (AET), symptom association probability (SAP), and symptom index (SI), as well as the quantity, pH, nature of reflux, its spread, and acid clearance time, alongside innovative measures such as mean nocturnal baseline impedance (MNBI) and post- reflux induced peristaltic wave index (PSWPI), is pivotal in precisely delineating reflux patterns and identifying the temporal connection between non-acid reflux occurrences and episodes of coughing. The prevailing reliance on proton pump inhibitors (PPIs) for treatment has encountered constraints in effectively managing non-acid GERC, underscoring the necessity for personalized treatment modalities that confront the unique pathophysiology of non-acid GERC to ameliorate patient outcomes. As research continues to deepen our understanding and enhance treatment methods for this multifaceted condition, the pursuit of effective treatment strategies becomes crucial. Our review aims to delineate the spectrum of therapeutic options, advancements in diagnostics, and an improved grasp of the pathogenesis of non-acid GERD. The focus of this review is to further the advancement of patient care management and to inspire continued research in this intriguing domain of gastroenterology.

Keywords : GERC, GERD, MII-pH Monitoring, Chronic Cough, MNBI

References :

  1. Kahrilas P J, Altman K W, Chang A B, et al. Chronic Cough Due to Gastroesophageal Reflux in Adults: CHEST Guideline and Expert Panel Report. Chest, 2016, 150(6): 1341-1360.
  2. Sifrim D, Mittal R, Fass R, et al. Review article: acidity and volume of the refluxate in the genesis of gastro-oesophageal reflux disease symptoms. Aliment Pharmacol Ther, 2007, 25(9): 1003-1017.
  3. Sifrim D, Dupont L, Blondeau K, et al. Weakly acidic reflux in patients with chronic unexplained cough during 24 hour pressure, pH, and impedance monitoring. Gut, 2005, 54(4): 449-454.
  4. Irwin R S. Chronic cough due to gastroesophageal reflux disease: ACCP evidence-based clinical practice guidelines. Chest, 2006, 129(1 Suppl): 80s-94s.
  5. Dong R, Xu X, Yu L, et al. Randomised clinical trial: gabapentin vs baclofen in the treatment of suspected refractory gastro-oesophageal reflux-induced chronic cough. Alimentary Pharmacology & Therapeutics, 2019, 49(6): 714-722.
  6. Lai K. Chinese National Guidelines on Diagnosis and Management of Cough: consensus and controversy. Journal of Thoracic Disease, 2014: S683-S688.
  7. Chung K F, Pavord I D. Prevalence, pathogenesis, and causes of chronic cough. Lancet, 2008, 371(9621): 1364-1374.
  8. Francis D O, Rymer J A, Slaughter J C, et al. High economic burden of caring for patients with suspected extraesophageal reflux. Am J Gastroenterol, 2013, 108(6): 905-911.
  9. El-Serag H B, Sweet S, Winchester C C, et al. Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut, 2014, 63(6): 871-880.
  10. Niimi A. Cough associated with gastro-oesophageal reflux disease (GORD): Japanese experience. Pulm Pharmacol Ther, 2017, 47: 59-65.
  11. Ding H, Xu X, Wen S, et al. Changing etiological frequency of chronic cough in a tertiary hospital in Shanghai, China. J Thorac Dis, 2019, 11(8): 3482-3489.
  12. Wu J, Ma Y, Chen Y. GERD-related chronic cough: Possible mechanism, diagnosis and treatment. Front Physiol, 2022, 13: 1005404.
  13. Irwin R S, Zawacki J K, Curley F J, et al. Chronic cough as the sole presenting manifestation of gastroesophageal reflux. Am Rev Respir Dis, 1989, 140(5): 1294-1300.
  14. Irwin R S, Curley F J, French C L. Chronic cough. The spectrum and frequency of causes, key components of the diagnostic evaluation, and outcome of specific therapy. Am Rev Respir Dis, 1990, 141(3): 640-647.
  15. Palombini B C, Villanova C A, Araújo E, et al. A pathogenic triad in chronic cough: asthma, postnasal drip syndrome, and gastroesophageal reflux disease. Chest, 1999, 116(2): 279-284.
  16. Mcgarvey L, Forsythe P, Heaney L, et al. Bronchoalveolar lavage findings in patients with chronic nonproductive cough. European Respiratory Journal, 1999, 13(1): 59-65.
  17. Ing A J, Ngu M C, Breslin A B. Chronic persistent cough and gastro-oesophageal reflux . Thorax, 1991, 46(7): 479-483.
  18. Poe R H, Harder R V, Israel R H, et al. Chronic persistent cough. Experience in diagnosis and outcome using an anatomic diagnostic protocol. Chest, 1989, 95(4): 723-728.
  19. Irwin R S, Boulet L P, Cloutier M M, et al. Managing cough as a defense mechanism and as a symptom. A consensus panel report of the American College of Chest Physicians. Chest, 1998, 114(2 Suppl Managing): 133s-181s.
  20. Ing A J, Ngu M C, Breslin A B. Pathogenesis of chronic persistent cough associated with gastroesophageal reflux. Am J Respir Crit Care Med, 1994, 149(1): 160-167.
  21. Harding S M, Richter J E. The role of gastroesophageal reflux in chronic cough and asthma. Chest, 1997, 111(5): 1389-1402.
  22. Mello C J, Irwin R S, Curley F J. Predictive values of the character, timing, and complications of chronic cough in diagnosing its cause. Arch Intern Med, 1996, 156(9): 997-1003.
  23. Irwin R S, French C L, Curley F J, et al. Chronic cough due to gastroesophageal reflux. Clinical, diagnostic, and pathogenetic aspects. Chest, 1993, 104(5): 1511-1517.
  24. Irwin R S, Rippe J M, Ovid Technologies I. Irwin and Rippe's intensive care medicine [M/OL]. 2003
  25. Smyrnios N A, Irwin R S, Curley F J. Chronic cough with a history of excessive sputum production. The spectrum and frequency of causes, key components of the diagnostic evaluation, and outcome of specific therapy. Chest, 1995, 108(4): 991-997.
  26. Kahrilas P J, Altman K W, Chang A B, et al. Chronic Cough Due to Gastroesophageal Reflux in Adults: CHEST Guideline and Expert Panel Report. Chest, 2016, 150(6): 1341-1360.
  27. Zerbib F, Roman S, Ropert A, et al. Esophageal pH-impedance monitoring and symptom analysis in GERD: a study in patients off and on therapy. Am J Gastroenterol, 2006, 101(9): 1956-1963.
  28. Boeckxstaens G E, Smout A. Systematic review: role of acid, weakly acidic and weakly alkaline reflux in gastro-oesophageal reflux disease. Aliment Pharmacol Ther, 2010, 32(3): 334-343.
  29. Sifrim D, Dupont L, Blondeau K, et al. Weakly acidic reflux in patients with chronic unexplained cough during 24 hour pressure, pH, and impedance monitoring. Gut, 2005, 54(4): 449-454.
  30. Xu X, Yang Z, Chen Q, et al. Comparison of clinical characteristics of chronic cough due to non-acid and acid gastroesophageal reflux. Clin Respir J, 2015, 9(2): 196-202.
  31. Agrawal A, Roberts J, Sharma N, et al. Symptoms with acid and nonacid reflux may be produced by different mechanisms. Dis Esophagus, 2009, 22(5): 467-470.
  32. Niimi A, Torrego A, Nicholson A G, et al. Nature of airway inflammation and remodeling in chronic cough. J Allergy Clin Immunol, 2005, 116(3): 565-570.
  33. Qiu Z, Yu L, Xu S, et al. Cough reflex sensitivity and airway inflammation in patients with chronic cough due to non-acid gastro-oesophageal reflux. Respirology, 2011, 16(4): 645-652.
  34. Patterson N, Mainie I, Rafferty G, et al. Nonacid reflux episodes reaching the pharynx are important factors associated with cough. J Clin Gastroenterol, 2009, 43(5): 414-419.
  35. Park H J, Park Y M, Kim J-H, et al. Effectiveness of proton pump inhibitor in unexplained chronic cough. PLOS ONE, 2017, 12(10): e0185397.
  36. Yu L, Xu X, Hang J, et al. Efficacy of sequential three-step empirical therapy for chronic cough. Ther Adv Respir Dis, 2017, 11(6): 225-232.
  37. Mainie I, Tutuian R, Agrawal A, et al. Fundoplication eliminates chronic cough due to non-acid reflux identified by impedance pH monitoring. Thorax, 2005, 60(6): 521-523.
  38. Ghezzi M, Guida E, Ullmann N, et al. Weakly acidic gastroesophageal refluxes are frequently triggers in young children with chronic cough. Pediatric Pulmonology, 2013, 48(3): 295-302.
  39. Oelschlager B K, Quiroga E, Isch J A, et al. Gastroesophageal and pharyngeal reflux detection using impedance and 24-hour pH monitoring in asymptomatic subjects: defining the normal environment. J Gastrointest Surg, 2006, 10(1): 54-62.
  40. Herregods T V K, Pauwels A, Jafari J, et al. Determinants of reflux-induced chronic cough [J]. Gut, 2017, 66(12): 2057-2062.
  41. Ravelli A M, Panarotto M B, Verdoni L, et al. Pulmonary aspiration shown by scintigraphy in gastroesophageal reflux-related respiratory disease. Chest, 2006, 130(5): 1520-1526.
  42. Phua S Y, Mcgarvey L P, Ngu M C, et al. Patients with gastro-oesophageal reflux disease and cough have impaired laryngopharyngeal mechanosensitivity. Thorax, 2005, 60(6): 488-491.
  43. Farrell S, Mcmaster C, Gibson D, et al. Pepsin in bronchoalveolar lavage fluid: a specific and sensitive method of diagnosing gastro-oesophageal reflux-related pulmonary aspiration. J Pediatr Surg, 2006, 41(2): 289-293.
  44. Özdemir P, Erdinç M, Vardar R, et al. The Role of Microaspiration in the Pathogenesis of Gastroesophageal Reflux-related Chronic Cough. J Neurogastroenterol Motil, 2017, 23(1): 41-48.
  45. Grabowski M, Kasran A, Seys S, et al. Pepsin and bile acids in induced sputum of chronic cough patients. Respir Med, 2011, 105(8): 1257-1261.
  46. Decalmer S, Stovold R, Houghton L A, et al. Chronic cough: relationship between microaspiration, gastroesophageal reflux, and cough frequency. Chest, 2012, 142(4): 958-964.
  47. Ziora D, Jarosz W, Dzielicki J, et al. Citric acid cough threshold in patients with gastroesophageal reflux disease rises after laparoscopic fundoplication. Chest, 2005, 128(4): 2458-2464.
  48. Torrego A, Cimbollek S, Hew M, et al. No effect of omeprazole on pH of exhaled breath condensate in cough associated with gastro-oesophageal reflux. Cough, 2005, 1: 10.
  49. Patterson R N, Johnston B T, Ardill J E, et al. Increased tachykinin levels in induced sputum from asthmatic and cough patients with acid reflux. Thorax, 2007, 62(6): 491-495.
  50. Laukka M A, Cameron A J, Schei A J. Gastroesophageal reflux and chronic cough: which comes first?. J Clin Gastroenterol, 1994, 19(2): 100-104.
  51. Sifrim D, Castell D, Dent J, et al. Gastro-oesophageal reflux monitoring: review and consensus report on detection and definitions of acid, non-acid, and gas reflux. Gut, 2004, 53(7): 1024-1031.
  52. Prakash C, Jonnalagadda S. Esophageal impedance testing: unraveling the mysteries of gastroesophageal reflux. Gastroenterology, 2006, 131(1): 322-323.
  53. Gyawali C P, Carlson D A, Chen J W, et al. ACG Clinical Guidelines: Clinical Use of Esophageal Physiologic Testing. Am J Gastroenterol, 2020, 115(9): 1412-1428.
  54. Blondeau K, Dupont L J, Mertens V, et al. Improved diagnosis of gastro-oesophageal reflux in patients with unexplained chronic cough. Aliment Pharmacol Ther, 2007, 25(6): 723-732.
  55. Roman S, Gyawali C P, Savarino E, et al. Ambulatory reflux monitoring for diagnosis of gastro-esophageal reflux disease: Update of the Porto consensus and recommendations from an international consensus group. Neurogastroenterol Motil, 2017, 29(10): 1-15.
  56. Bogte A, Bredenoord A J, Smout A J. Diagnostic yield of oesophageal pH monitoring in patients with chronic unexplained cough. Scand J Gastroenterol, 2008, 43(1): 13-19.
  57. Bredenoord A J, Weusten B L, Timmer R, et al. Addition of esophageal impedance monitoring to pH monitoring increases the yield of symptom association analysis in patients off PPI therapy. Am J Gastroenterol, 2006, 101(3): 453-459.
  58. Hemmink G J, Bredenoord A J, Weusten B L, et al. Esophageal pH-impedance monitoring in patients with therapy-resistant reflux symptoms: 'on' or 'off' proton pump inhibitor?. Am J Gastroenterol, 2008, 103(10): 2446-2453.
  59. Weusten B L, Roelofs J M, Akkermans L M, et al. The symptom-association probability: an improved method for symptom analysis of 24-hour esophageal pH data. Gastroenterology, 1994, 107(6): 1741-1745.
  60. Smith J A, Decalmer S, Kelsall A, et al. Acoustic cough-reflux associations in chronic cough: potential triggers and mechanisms. Gastroenterology, 2010, 139(3): 754-762.
  61. Xu X, Yu L, Chen Q, et al. Diagnosis and treatment of patients with nonacid gastroesophageal reflux-induced chronic cough. J Res Med Sci, 2015, 20(9): 885-892.
  62. Neto R M L, Herbella F A M, Schlottmann F, et al. Does DeMeester score still define GERD?. Diseases of the Esophagus, 2019, 32(5): doy118.
  63. Zhu Y, Tang J, Shi W, et al. Can acid exposure time replace the DeMeester score in the diagnosis of gastroesophageal reflux-induced cough?. Therapeutic Advances in Chronic Disease, 2021, 12: 20406223211056719.
  64. Mainie I, Tutuian R, Castell D O. Comparison between the combined analysis and the DeMeester Score to predict response to PPI therapy. J Clin Gastroenterol, 2006, 40(7): 602-605.
  65. Wiener G J, Morgan T M, Copper J B, et al. Ambulatory 24-hour esophageal pH monitoring. Reproducibility and variability of pH parameters. Dig Dis Sci, 1988, 33(9): 1127-1133.
  66. Gyawali C P, Kahrilas P J, Savarino E, et al. Modern diagnosis of GERD: the Lyon Consensus. Gut, 2018, 67(7): 1351-1362.
  67. Ates F, Yuksel E S, Higginbotham T, et al. Mucosal impedance discriminates GERD from non-GERD conditions. Gastroenterology, 2015, 148(2): 334-343.
  68. Naik R D, Evers L, Vaezi M F. Advances in the Diagnosis and Treatment of GERD: New Tricks for an Old Disease [J]. Curr Treat Options Gastroenterol, 2019, 17(1): 1-17.
  69. Samuels T L, Johnston N. Pepsin as a marker of extraesophageal reflux. Ann Otol Rhinol Laryngol, 2010, 119(3): 203-208.
  70. Tack J, Koek G, Demedts I, et al. Gastroesophageal reflux disease poorly responsive to single-dose proton pump inhibitors in patients without Barrett's esophagus: acid reflux, bile reflux, or both?. Am J Gastroenterol, 2004, 99(6): 981-988.
  71. Frazzoni M, Savarino E, De Bortoli N, et al. Analyses of the Post-reflux Swallow-induced Peristaltic Wave Index and Nocturnal Baseline Impedance Parameters Increase the Diagnostic Yield of Impedance-pH Monitoring of Patients With Reflux Disease. Clin Gastroenterol Hepatol, 2016, 14(1): 40-46.
  72. Frazzoni M, De Bortoli N, Frazzoni L, et al. The added diagnostic value of postreflux swallow-induced peristaltic wave index and nocturnal baseline impedance in refractory reflux disease studied with on-therapy impedance-pH monitoring. Neurogastroenterology & Motility, 2017, 29(3): e12947.
  73. De Bortoli N, Martinucci I, Savarino E, et al. Association between baseline impedance values and response proton pump inhibitors in patients with heartburn. Clin Gastroenterol Hepatol, 2015, 13(6): 1082-1088.e1081.
  74. Frazzoni M, Manta R, Mirante V G, et al. Esophageal chemical clearance is impaired in gastro-esophageal reflux disease – a 24-h impedance-pH monitoring assessment. Neurogastroenterology & Motility, 2013, 25(5): 399-e295.
  75. Zikos T A, Clarke J O. Non-acid Reflux: When It Matters and Approach to Management. Curr Gastroenterol Rep, 2020, 22(9): 43.
  76. Frazzoni M, Savarino E, Manno M, et al. Reflux patterns in patients with short-segment Barrett's oesophagus: a study using impedance-pH monitoring off and on proton pump inhibitor therapy. Aliment Pharmacol Ther, 2009, 30(5): 508-515.
  77. Wang S, Wen S, Bai X, et al. Diagnostic value of reflux episodes in gastroesophageal reflux-induced chronic cough: a novel predictive indicator. Ther Adv Chronic Dis, 2022, 13: 20406223221117455.
  78. Kahrilas P J, Howden C W, Hughes N, et al. Response of chronic cough to acid-suppressive therapy in patients with gastroesophageal reflux disease. Chest, 2013, 143(3): 605-612.
  79. Martinucci I, De Bortoli N, Savarino E, et al. Esophageal baseline impedance levels in patients with pathophysiological characteristics of functional heartburn. Neurogastroenterol Motil, 2014, 26(4): 546-555.
  80. Xie C, Sifrim D, Li Y, et al. Esophageal Baseline Impedance Reflects Mucosal Integrity and Predicts Symptomatic Outcome With Proton Pump Inhibitor Treatment. J Neurogastroenterol Motil, 2018, 24(1): 43-50.
  81. Tenca A, De Bortoli N, Mauro A, et al. Esophageal chemical clearance and baseline impedance values in patients with chronic autoimmune atrophic gastritis and gastro-esophageal reflux disease. Dig Liver Dis, 2017, 49(9): 978-983.
  82. Yoshimine T, Funaki Y, Kawamura Y, et al. Convenient Method of Measuring Baseline Impedance for Distinguishing Patients with Functional Heartburn from those with Proton Pump Inhibitor-Resistant Endoscopic Negative Reflux Disease. Digestion, 2019, 99(2): 157-165.
  83. Patel A, Wang D, Sainani N, et al. Distal mean nocturnal baseline impedance on pH-impedance monitoring predicts reflux burden and symptomatic outcome in gastro-oesophageal reflux disease. Aliment Pharmacol Ther, 2016, 44(8): 890-898.
  84. Farré R, Blondeau K, Clement D, et al. Evaluation of oesophageal mucosa integrity by the intraluminal impedance technique. Gut, 2011, 60(7): 885-892.
  85. Kessing B F, Bredenoord A J, Weijenborg P W, et al. Esophageal acid exposure decreases intraluminal baseline impedance levels. Am J Gastroenterol, 2011, 106(12): 2093-2097.
  86. 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): 1075-1081.
  87. Zhong C, Duan L, Wang K, et al. Esophageal intraluminal baseline impedance is associated with severity of acid reflux and epithelial structural abnormalities in patients with gastroesophageal reflux disease. J Gastroenterol, 2013, 48(5): 601-610.
  88. Woodland P, Al-Zinaty M, Yazaki E, et al. In vivo evaluation of acid-induced changes in oesophageal mucosa integrity and sensitivity in non-erosive reflux disease. Gut, 2013, 62(9): 1256-1261.
  89. Wunderlich A W, Murray J A. Temporal correlation between chronic cough and gastroesophageal reflux disease. Dig Dis Sci, 2003, 48(6): 1050-1056.
  90. Matos S, Birring S S, Pavord I D, et al. An automated system for 24-h monitoring of cough frequency: the leicester cough monitor. IEEE Trans Biomed Eng, 2007, 54(8): 1472-1479.
  91. Smith J, Owen E, Earis J, Woodcock A. Effect of codeine on objective measurement of cough in chronic obstructive pulmonary disease. J Allergy Clin Immunol, 2006, 117(4): 831-835.
  92. Barry S J, Dane A D, Morice A H, et al. The automatic recognition and counting of cough. Cough, 2006, 2(1): 8.
  93. Coyle M A, Keenan D B, Henderson L S, et al. Evaluation of an ambulatory system for the quantification of cough frequency in patients with chronic obstructive pulmonary disease. Cough, 2005, 1: 3.
  94.  Zhonghua J, He H, Hu X, et al. Chinese national guideline on diagnosis and management of cough(2021), 2022, 45(1): 13-46.
  95. Li N, Chen Q, Wen S, et al. Diagnostic accuracy of multichannel intraluminal impedance-pH monitoring for gastroesophageal reflux-induced chronic cough. Chron Respir Dis, 2021, 18: 14799731211006682.
  96. Tutuian R, Mainie I, Agrawal A, et al. Nonacid reflux in patients with chronic cough on acid-suppressive therapy. Chest, 2006, 130(2): 386-391.
  97. Xiao Y, Liang M, Peng S, et al. Tailored therapy for the refractory GERD patients by combined multichannel intraluminal impedance-pH monitoring. J Gastroenterol Hepatol, 2016, 31(2): 350-354.
  98. Strugala V, Avis J, Jolliffe I G, et al. The role of an alginate suspension on pepsin and bile acids - key aggressors in the gastric refluxate. Does this have implications for the treatment of gastro-oesophageal reflux disease?. J Pharm Pharmacol, 2009, 61(8): 1021-1028.
  99. Ranaldo N, Losurdo G, Iannone A, et al. Tailored therapy guided by multichannel intraluminal impedance pH monitoring for refractory non-erosive reflux disease. Cell Death Dis, 2017, 8(9): e3040.
  100. Savarino E, De Bortoli N, Zentilin P, et al. Alginate controls heartburn in patients with erosive and nonerosive reflux disease. World J Gastroenterol, 2012, 18(32): 4371-4378.
  101. De Ruigh A, Roman S, Chen J, et al. Gaviscon Double Action Liquid (antacid & alginate) is more effective than antacid in controlling post-prandial oesophageal acid exposure in GERD patients: a double-blind crossover study. Aliment Pharmacol Ther, 2014, 40(5): 531-537.
  102. Dellon E S, Shaheen N J. Persistent reflux symptoms in the proton pump inhibitor era: the changing face of gastroesophageal reflux disease. Gastroenterology, 2010, 139(1): 7-13.e13.
  103. Ren L H, Chen W X, Qian L J, et al. Addition of prokinetics to PPI therapy in gastroesophageal reflux disease: a meta-analysis. World J Gastroenterol, 2014, 20(9): 2412-2419.
  104. Clarke J O, Fernandez-Becker N Q, Regalia K A, et al. Baclofen and gastroesophageal reflux disease: seeing the forest through the trees. Clin Transl Gastroenterol, 2018, 9(3): 137.
  105. Li S, Shi S, Chen F, Lin J. The effects of baclofen for the treatment of gastroesophageal reflux disease: a meta-analysis of randomized controlled trials. Gastroenterol Res Pract, 2014, 2014: 307805.
  106. Vela M F, Tutuian R, Katz P O, et al. Baclofen decreases acid and non-acid post-prandial gastro-oesophageal reflux measured by combined multichannel intraluminal impedance and pH. Aliment Pharmacol Ther, 2003, 17(2): 243-251.
  107. Beaumont H, Boeckxstaens G E. Does the presence of a hiatal hernia affect the efficacy of the reflux inhibitor baclofen during add-on therapy?. Am J Gastroenterol, 2009, 104(7): 1764-1771.
  108. Pauwels A, Broers C, Van Houtte B, et al. A Randomized Double-Blind, Placebo-Controlled, Cross-Over Study Using Baclofen in the Treatment of Rumination Syndrome. Am J Gastroenterol, 2018, 113(1): 97-104.
  109. Lee Y C, Jung A R, Kwon O E, et al. The effect of baclofen combined with a proton pump inhibitor in patients with refractory laryngopharyngeal reflux: A prospective, open-label study in thirty-two patients. Clin Otolaryngol, 2019, 44(3): 431-434.
  110. Dong R, Xu X, Yu L, et al. Randomised clinical trial: gabapentin vs baclofen in the treatment of suspected refractory gastro-oesophageal reflux-induced chronic cough. Aliment Pharmacol Ther, 2019, 49(6): 714-722.
  111. Tack J, Janssen P, Masaoka T, et al. Efficacy of buspirone, a fundus-relaxing drug, in patients with functional dyspepsia. Clin Gastroenterol Hepatol, 2012, 10(11): 1239-1245.
  112. Karamanolis G P, Panopoulos S, Denaxas K, et al. The 5-HT1A receptor agonist buspirone improves esophageal motor function and symptoms in systemic sclerosis: a 4-week, open-label trial. Arthritis Res Ther, 2016, 18(1): 195.
  113. Di Stefano M, Papathanasopoulos A, Blondeau K, et al. Effect of buspirone, a 5-HT1A receptor agonist, on esophageal motility in healthy volunteers. Dis Esophagus, 2012, 25(5): 470-476.
  114. Jeansonne L O t, White B C, Nguyen V, et al. Endoluminal full-thickness plication and radiofrequency treatments for GERD: an outcomes comparison. Arch Surg, 2009, 144(1): 19-24; discussion 24.
  115. Mainie I, Tutuian R, Agrawal A, et al. Combined multichannel intraluminal impedance-pH monitoring to select patients with persistent gastro-oesophageal reflux for laparoscopic Nissen fundoplication. Br J Surg, 2006, 93(12): 1483-1487.
  116. Sidwa F, Moore A L, Alligood E, et al. Surgical Treatment of Extraesophageal Manifestations of Gastroesophageal Reflux Disease. World J Surg, 2017, 41(10): 2566-2571.
  117. Desjardin M, Luc G, Collet D, et al 24-hour pH-impedance monitoring on therapy to select patients with refractory reflux symptoms for antireflux surgery. A single center retrospective study. Neurogastroenterol Motil, 2016, 28(1): 146-152.
  118. Savarino E, Marabotto E, Salvador R, et al. Mo1117 Patients With Non-Acid Reflux Disease and Those With Erosive and Non-Erosive Reflux Disease Have Similar Response to Anti-Reflux Surgical Therapy. Gastroenterology, 2015, 148: S-611.
  119. Lv H J, Qiu Z M. Refractory chronic cough due to gastroesophageal reflux: Definition, mechanism and management. World J Methodol, 2015, 5(3): 149-156.
  120. Zhu Y, Xu X, Zhang M, et al. Pressure and length of the lower esophageal sphincter as predictive indicators of therapeutic efficacy of baclofen for refractory gastroesophageal reflux-induced chronic cough. Respir Med, 2021, 183: 106439.
  121. Zhang M, Chen Q, Dong R, et al. Prediction of therapeutic efficacy of gabapentin by Hull Airway Reflux Questionnaire in chronic refractory cough. Ther Adv Chronic Dis, 2020, 11: 2040622320982463.
  122. Liu J, Deng C, Zhang M, et al. Laparoscopic fundoplication in treating refractory gastroesophageal reflux-related chronic cough: A meta-analysis. Medicine (Baltimore), 2023, 102(20): e33779.

Total Recent investigations have highlighted the pivotal influence of non-acid reflux in the etiology of chronic cough associated with gastroesophageal reflux disease (GERC). Differentiation between acid and non- acid GERC is effectively achieved through esophageal pH monitoring, with non-acid reflux drawing attention for its linkage to non-standard symptoms and the intricacies involved in its management. The combination of multi-channel intraluminal impedance with pH monitoring (MII-PH) and its related metrics, including acid exposure time (AET), symptom association probability (SAP), and symptom index (SI), as well as the quantity, pH, nature of reflux, its spread, and acid clearance time, alongside innovative measures such as mean nocturnal baseline impedance (MNBI) and post- reflux induced peristaltic wave index (PSWPI), is pivotal in precisely delineating reflux patterns and identifying the temporal connection between non-acid reflux occurrences and episodes of coughing. The prevailing reliance on proton pump inhibitors (PPIs) for treatment has encountered constraints in effectively managing non-acid GERC, underscoring the necessity for personalized treatment modalities that confront the unique pathophysiology of non-acid GERC to ameliorate patient outcomes. As research continues to deepen our understanding and enhance treatment methods for this multifaceted condition, the pursuit of effective treatment strategies becomes crucial. Our review aims to delineate the spectrum of therapeutic options, advancements in diagnostics, and an improved grasp of the pathogenesis of non-acid GERD. The focus of this review is to further the advancement of patient care management and to inspire continued research in this intriguing domain of gastroenterology.

Keywords : GERC, GERD, MII-pH Monitoring, Chronic Cough, MNBI

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