Characteristics of symptomatic reflux episodes in Japanese proton pump inhibitor-refractory non-erosive reflux disease patients

Nakagawa, Kenichiro; Koike, Tomoyuki; Iijima, Katsunori; Saito, Masahiro; Kikuchi, H; Hatta, Waku; Ara, Nobuyuki; Uno, Kaname; Asano, Naoki; Shimosegawa, Tooru

doi:10.3748/wjg.v21.i47.13352

Cited by 7 publications

(13 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A previous study demonstrated that proximal spread of weakly acid reflux determines the perception of reflux in GERD patients without apparent esophageal injury on PPI therapy [21, 22]. Then, we recently revealed that the proximal extent of weakly acidic reflux is critical to the perception of reflux in patients with nonerosive reflux disease despite the use of PPIs [23]. Thus, we hypothesized that an alternation in esophageal mucosal integrity by location could be associated with acid hypersensitivity, which causes reflux perception in the patients.…”

Section: Introductionmentioning

confidence: 99%

Impaired Mucosal Integrity in Proximal Esophagus Is Involved in Development of Proton Pump Inhibitor-Refractory Nonerosive Reflux Disease

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background and Objective: Weakly acidic reflux reaching to the proximal esophagus is closely related to the perception of gastroesophageal reflux in patients with nonerosive reflux disease despite treatment with a proton pump inhibitor (PPI). However, little is known about the involvement of the patients’ mucosal integrity of the proximal esophagus. Methods: We recruited 15 symptomatic nonerosive gastroesophageal reflux disease (GERD) patients with a positive symptom index despite PPI treatment and 11 healthy asymptomatic volunteers as controls. The biopsy specimens obtained from the proximal and distal esophagus were applied to a mini-Ussing chamber system to measure transepithelial electrical resistance (TEER) against a pH 4 weak acid. The esophageal biopsy samples were subjected to quantitative real-time PCR and immunohistochemical analysis. Results: In the proximal esophagus, the weak acid exposure reduced the TEER in the PPI-refractory patients compared to that in the controls. The frequency of the reflux extending to the proximal esophagus had a significant correlation with the reduction in the proximal esophageal TEER in the patients. The reduced TEER in the proximal esophagus was accompanied by an increase in IL-8 and IL-1β mRNA and a decrease in occludin mRNA levels. The proximal esophageal mucosa in the patients presented infiltration of CD3-positive lymphocytes and an increased expression of solute carrier organic anion transporter family member 2A1 (SLCO2A1), a passage gate of reflux symptom-evoking molecules. Conclusions: The reflux perception is related to an impairment of the proximal esophageal mucosal integrity in patients with nonerosive reflux disease despite PPI.

show abstract

Section: Introductionmentioning

confidence: 99%

Impaired Mucosal Integrity in Proximal Esophagus Is Involved in Development of Proton Pump Inhibitor-Refractory Nonerosive Reflux Disease

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…The PPI responsiveness in patients with NERD was reported to be < 60% [3]. Although the mechanisms of reflux perception remain unclear, patients with NERD have been reported to be more hyper-DOI: 10.1159/000500133 sensitive to visceral stimulation than those with ERD due to a reduced pain threshold [4][5][6]. Therefore, NERD is not just a mild form of ERD.…”

Section: Introductionmentioning

confidence: 99%

“…The advent of combined multichannel intraluminal impedance and pH (MII-pH) monitoring made possible the detection of non-acidic and acidic refluxes [7]. Recent studies have demonstrated that weakly acidic reflux (reflux of pH 4-7) was the major cause of symptom occurrence in patients with PPI-refractory NERD who underwent PPI treatment [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Abe¹,

Koike²,

Saito³

et al. 2019

Digestion

Self Cite

View full text Add to dashboard Cite

Background and Objectives: Weakly acidic reflux has been reported as the major cause of symptom occurrence in patients with proton pump inhibitor (PPI)-refractory non-erosive reflux disease (NERD). This study is aimed at clarifying whether the pH value of weakly acidic reflux affects the induction of symptoms. Methods: We retrospectively evaluated the records of combined multichannel intraluminal impedance and pH monitoring in 57 patients with PPI-refractory NERD. Weakly acidic refluxes were divided into 3 categories based on the pH value of the refluxate: pH 4-5, 5-6, and 6-7. Results: A total of 29 patients were positive in the symptom index. The symptom provocation rate in reflux of pH 4-5 (19%) was much higher than in that of pH 5-6 (11%) and pH 6-7 (12%). In the reflux at pH 4-5, the symptom provocation rate in the proximal reflux was higher than that in the distal reflux (p < 0.05), whereas the reflux at pH 5-6 and pH 6-7 was not significantly different in the symptom provocation rate between the proximal and distal refluxes. Conclusion: Reflux at pH < 5 reaching the proximal esophagus was the main factor in the induced symptoms of patients with PPI-refractory NERD.

show abstract

“… 6 However, some authors believe that lack of clinical response after a 8-week course of PPI may be sufficient to define refractoriness for NERD. 7 , 8 Refractory NERD is often a therapeutic challenge. Indeed, in a systematic review, pooled rate of symptomatic response to PPI was 36.7% (95% confidence interval: 34.1–39.3) in NERD and 55.5% (95% confidence interval: 51.5–59.5) in erosive esophagitis.…”

mentioning

confidence: 99%

Tailored therapy guided by multichannel intraluminal impedance pH monitoring for refractory non-erosive reflux disease

et al. 2017

View full text Add to dashboard Cite

A relevant percentage of non-erosive reflux disease (NERD) is refractory to proton pump inhibitors (PPIs) treatment. Multichannel intraluminal impedance pH (MII-pH) monitoring should give useful pathophysiological information about refractoriness. Therefore, our aim was to assess whether this technique could be useful to guide a 'tailored' therapy in refractory NERD. We retrospectively recruited NERD patients undergoing MII-pH monitoring for unsuccessful treatment. All patients had undergone upper endoscopy, and those with erosive esophagitis were excluded. No patient received PPI during MII-pH monitoring. Subjects were subgrouped into three categories: acid reflux, non-acid reflux and functional heartburn. MII-pH-guided therapy was performed for 4 weeks as follows: patients with acid reflux received PPI at double dose, patients with non-acid reflux PPI at full dose plus alginate four times a day and patients with functional heartburn levosulpiride 75 mg per day. A visual analog scale (VAS) ranging from 0 to 100 mm was administered before and after such tailored therapy to evaluate overall symptoms. Responders were defined by VAS improvement of at least 40%. Sixty-nine patients with refractory NERD were selected (female–male ratio 43 : 26, mean age 47.6±15.2 years). Overall effectiveness of tailored therapy was 84% without statistical difference among subgroups (88.5% acid reflux, 92% non-acid reflux, 66.6% functional heartburn; P=0.06). Univariate analysis showed that therapy failure directly correlated with functional heartburn diagnosis (OR=4.60) and suggested a trend toward a negative correlation with smoking and a positive one with nausea. However, at multivariate analysis, these parameters were not significant. Functional heartburn experienced a lower median percent VAS reduction than acid reflux (52.5% versus 66.6%, P<0.01) even if equal to non-acid reflux (66.6%). In conclusion, a tailored approach to refractory NERD, guided by MII-pH monitoring, demonstrated to be effective and should be promising to cure symptom persistence after conventional therapy failure. Nevertheless, standardized guidelines are advisable.

show abstract

Characteristics of symptomatic reflux episodes in Japanese proton pump inhibitor-refractory non-erosive reflux disease patients

Abstract: The proximal extent of weakly acidic liquid and mixed liquid-gas reflux is a major factor associated with reflux perception in SI-positive patients on proton pump inhibitor therapy.

Cited by 7 publications

References 27 publications

Impaired Mucosal Integrity in Proximal Esophagus Is Involved in Development of Proton Pump Inhibitor-Refractory Nonerosive Reflux Disease

Impaired Mucosal Integrity in Proximal Esophagus Is Involved in Development of Proton Pump Inhibitor-Refractory Nonerosive Reflux Disease

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

Tailored therapy guided by multichannel intraluminal impedance pH monitoring for refractory non-erosive reflux disease

Contact Info

Product

Resources

About