Influence of the pH Value of Refluxate and Proximal Extent on Heartburn Perception in Patients with Proton Pump Inhibitor-Refractory Non-Erosive Reflux Disease

Abe, Yuina; Koike, Tomoyuki; Saito, Masahiro; Okata, Tomoki; Norita, Kazuaki; Kikuchi, H; Nakagawa, Kenichiro; Hatta, Waku; Asanuma, Kiyotaka; Uno, Kaname; Asano, Naoki; Imatani, Akira; Shimosegawa, Tooru; Masamune, Atsushi

doi:10.1159/000500133

Cited by 7 publications

(8 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Along the same lines, several studies have reported that weakly acidic reflux is one of the most relevant underlying causes of PPI-refractory NERD (for review see [96]). In addition, it was shown that the reflux events at pH 4-5, reaching the proximal esophagus, were the main symptom trigger in these patients [97]. Indeed, the pH of weakly acidic reflux represents a determining factor in provoking heartburn [98].…”

Section: Vonoprazan For Gerd: Conclusionmentioning

confidence: 97%

Acid Suppressant Therapy: a Step Forward with Potassium-Competitive Acid Blockers

Scarpignato

Hunt

2021

Curr Treat Options Gastro

View full text Add to dashboard Cite

Purpose of the review The introduction of H2-receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) into clinical practice has been a real breakthrough in the treatment of acid-related diseases. PPIs are now the standard of care for the treatment of gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), Helicobacter pylori infection, NSAID-associated gastroduodenal lesions, and upper gastrointestinal bleeding (UGIB). However, despite their effectiveness, PPIs display some intrinsic limitations, which underlie the unmet clinical needs that have been identified over the past decades. Recent findings To address these needs, new long-acting compounds (such as tenatoprazole and AGN 201904-Z) and new PPI formulations, including instant release omeprazole (IR-omeprazole) and dexlansoprazole modified release (MR), have been developed. However, a major advance has been the development of the potassium-competitive acid blockers (P-CABs), which block the K+,H+-ATPase potassium channel, are food independent, are reversible, have a rapid onset of action, and maintain a prolonged and consistent elevation of intragastric pH. Vonoprazan and tegoprazan are the two marketed P-CABs while two other compounds (namely fexuprazan and X842) are under active development. Available for almost 6 years now, a considerable experience has been accumulated with vonoprazan, the efficacy and safety of which are detailed in this paper, together with the preliminary results of the other members of this new pharmacologic class. Summary Based on the available evidence, erosive reflux disease, H. pylori infection, and secondary prevention of NSAID gastropathy can be considered established indications for vonoprazan and are being explored for tegoprazan and fexuprazan. In the treatment of severe (LA C & D) reflux esophagitis and H. pylori eradication, vonoprazan proved to be superior to PPIs. Other uses of P-CABs are being evaluated, but clinical data are not yet sufficient to allow a definitive answer on its efficacy and possible superiority over the current standard of care (i.e., PPIs). The most notable indication of upper GI (non-variceal) bleeding, where vonoprazan would prove superior to PPIs, has not yet been explored. The safety of P-CABs in the short-term overlaps that of PPIs, but data from long-term treatment are needed.

show abstract

Section: Vonoprazan For Gerd: Conclusionmentioning

confidence: 97%

Acid Suppressant Therapy: a Step Forward with Potassium-Competitive Acid Blockers

Scarpignato

Hunt

2021

Curr Treat Options Gastro

View full text Add to dashboard Cite

show abstract

“…Thus, the importance of strong acid suppressive therapy in patients with troublesome reflux symptoms despite PPI use has not been elucidated fully, and no study has evaluated the relationship between changes in the pH value of the refluxate and symptom induction after switching from PPI to VPZ using MII-pH monitoring. We previously reported that reflux at pH < 5 was the major cause of symptom occurrence in patients with PPI refractory NERD while taking double-dose PPI [8]. Therefore, we presumed that by switching to VPZ, which is expected to have a stronger acid suppressive effect than conventional PPI, the ratio of reflux at pH < 5 would decrease, and the troublesome reflux symptoms would improve.…”

Section: Discussionmentioning

confidence: 98%

“…However, few studies have focused on whether the frequency of reflux symptoms differs according to the pH value of weakly acidic reflux. Recently, we reported that reflux at pH 4-5 was the main factor that induced symptoms in patients with PPI-refractory NERD who underwent double-dose PPI [8]. Therefore, we thought that maintenance of the pH value of the refluxate at ≥5 could improve the symptoms of patients with PPI-refractory NERD.…”

Section: Introductionmentioning

confidence: 99%

The Ameliorating Effect of Switching to Vonoprazan: A Novel Potassium-Competitive Acid Blocker in Patients with Proton Pump Inhibitor Refractory Non-Erosive Reflux Disease

et al. 2020

Self Cite

View full text Add to dashboard Cite

Introduction: Weakly acidic reflux has been reported to be the major cause of symptoms in patients with proton pump inhibitor (PPI)-refractory nonerosive reflux disease (NERD) undergoing PPI treatment. We previously reported that reflux at pH 4–5 was the main factor that induced symptoms in such patients. The present study aimed to elucidate the symptom-ameliorating effect of vonoprazan (VPZ) by evaluating the change in the pH value of the refluxate using multichannel intraluminal impedance and pH (MII-pH) monitoring. Methods: We retrospectively evaluated the records of MII-pH monitoring in 29 symptom index (SI) and/or symptom association probability (SAP)-positive patients with PPI-refractory NERD. After switching to VPZ 20 mg/day, we performed MII-pH monitoring again. We assessed the change in the score of the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), the pH value of the refluxate, and the percent times of intragastric pH <4 or <5 before and after switching. We divided the patients into the following 2 groups according to the FSSG score after switching: effective and noneffective groups. Results: Among of the 29 SI/SAP-positive patients, 16 underwent switching to VPZ. Furthermore, of these 16 patients, 10 underwent MII-pH monitoring again after switching. The FSSG score decreased, the pH value of the refluxate increased, and the percent times of intragastric pH <4 or <5 reduced after switching when compared with the findings before switching. In the effective group, both the proportion of reflux at pH <4 and that of reflux at pH 4–5 decreased while taking VPZ when compared with the findings while taking double-dose PPI. In the noneffective group, the proportion of reflux at pH <4 decreased but that of reflux at pH 4–5 increased and that of reflux at pH <5 did not change overall while taking VPZ. In addition, the percent times of intragastric pH <5 values were low in the effective group. Conclusion: Symptom suppression appears to be inadequate in patients with persistent reflux at pH 4–5 even with VPZ 20 mg/day. Strong acid suppressive therapy with VPZ to increase the pH value of the refluxate to ≥5 is useful for symptom improvement.

show abstract

“…PGE 2 is involved in the induction of heartburn symptoms 14,26 . Interestingly, heartburn symptoms were most frequently reported when weak acid was refluxed, especially at pH 5, in patients with PPI-refractory GERD 10,11 . Moreover, the administration of weak acids (pH 4-5) induced heartburn symptoms in nearly 50% of patients with GERD symptoms 27 .…”

Section: Discussionmentioning

confidence: 99%

“…Advanced techniques for the measurement of oesophageal pH have shown that reflux events with values other than pH < 4, such as weak acids (i.e., pH 4-7), are possible responsible substances related to various GERD symptoms 7 . Several studies have reported that weak acids contribute to the pathogenesis of GERD symptoms in patients with proton pump inhibitor (PPI)-refractory GERD, which are considered problematic among the majority of clinicians [8][9][10][11][12] . Despite recent evidence for the role of weak acid reflux, the degree of risk and mechanisms by which it leads to GERD-related symptoms remain unclear.…”

mentioning

confidence: 99%

Weak acids induce PGE2 production in human oesophageal cells: novel mechanisms underlying GERD symptoms

Sadatomi

Kono

Mogami

et al. 2020

Sci Rep

View full text Add to dashboard Cite

The role of weak acids with pH values in the range of 4–7 has been implicated in the symptoms of gastroesophageal reflux disease (GERD). Prostaglandin E2 (PGE2) is associated with heartburn symptom in GERD patients; however, the precise productive mechanisms remain unclear. In this study, we revealed that exposure to weak acids increases PGE2 production with a peak at pH 4–5, slightly in human normal oesophageal cells (Het-1A), and robustly in oesophageal squamous carcinoma cells (KYSE-270). Release of PGE2 from the oesophageal mucosa was augmented by weak acid treatment in rat. Chenodeoxycholic acid (CDCA), a bile acid, upregulated cyclooxygenase-2 (COX-2) expression in Het-1A and KYSE-270 and induced PGE2 production in KYSE-270 cells. Weak acid-induced PGE2 production was significantly inhibited by cytosolic phospholipase A2 (cPLA2), ERK, and transient receptor potential cation channel subfamily V member 4 (TRPV4), a pH-sensing ion channel, inhibitors. Hangeshashinto, a potent inhibitor of COX-2, strongly decreased weak acid- and CDCA-induced PGE2 levels in KYSE-270. These results indicated that weak acids induce PGE2 production via TRPV4/ERK/cPLA2 in oesophageal epithelial cells, suggesting a role in GERD symptoms like heartburn. Interventions targeting pH values up to 5 may be necessary for the treatment of GERD.

show abstract

Influence of the pH Value of Refluxate and Proximal Extent on Heartburn Perception in Patients with Proton Pump Inhibitor-Refractory Non-Erosive Reflux Disease

Cited by 7 publications

References 30 publications

Acid Suppressant Therapy: a Step Forward with Potassium-Competitive Acid Blockers

Acid Suppressant Therapy: a Step Forward with Potassium-Competitive Acid Blockers

The Ameliorating Effect of Switching to Vonoprazan: A Novel Potassium-Competitive Acid Blocker in Patients with Proton Pump Inhibitor Refractory Non-Erosive Reflux Disease

Weak acids induce PGE2 production in human oesophageal cells: novel mechanisms underlying GERD symptoms

Contact Info

Product

Resources

About