In vivo evaluation of acid-induced changes in oesophageal mucosa integrity and sensitivity in non-erosive reflux disease

Woodland, Philip; Al-Zinaty, M; Yazaki, Etsuro; Sifrim, Daniel

doi:10.1136/gutjnl-2012-302645

Cited by 113 publications

(121 citation statements)

References 28 publications

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“…However, they also showed that physicians often do not pay attention to a negative pH study continuing to prescribe PPIs and even sending their patients to antireflux surgery, as already observed in our previous study. 28 Furthermore our findings suggest that previous studies looking at morphological and/or pathophysiological differences between FH and NERD, diagnosed with 24-hour pH/pH-impedance studies, [10][11][12][13][14] may have been inaccurate. Structural characteristics, which are devoid of day to day fluctuations, ie, histopathological parameters or basal impedance, could be the best variables in order to diagnose FH, but their diagnostic performance needs to be evaluated against a gold standard.…”

Section: Discussionmentioning

confidence: 59%

Inconsistency in the Diagnosis of Functional Heartburn: Usefulness of Prolonged Wireless pH Monitoring in Patients With Proton Pump Inhibitor Refractory Gastroesophageal Reflux Disease

Penagini

Sweis

Mauro

et al. 2015

J Neurogastroenterol Motil

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Background/Aims The diagnosis of functional heartburn is important for management, however it stands on fragile pH monitoring variables, ie, acid exposure time varies from day to day and symptoms are often few or absent. Aim of this study was to investigate consistency of the diagnosis of functional heartburn in subsequent days using prolonged wireless pH monitoring and its impact on patients’ outcome. Methods Fifty proton pump inhibitotor refractory patients (11 male, 48 years [range, 38–57 years]) with a diagnosis of functional heart-burn according to Rome III in the first 24 hours of wireless pH monitoring were reviewed. pH variables were analysed in the following 24-hour periods to determine if tracings were indicative of diagnosis of non-erosive reflux disease (either acid exposure time > 5% or normal acid exposure time and symptom index ≥ 50%). Outcome was assessed by review of hospital files and/or telephone interview. Results Fifteen out of 50 patients had a pathological acid exposure time after the first day of monitoring (10 in the second day and 5 in subsequent days), which changed their diagnosis from functional heartburn to non-erosive reflux disease. Fifty-four percent of non-erosive reflux disease vs 11% of functional heartburn patients ( P < 0.003) increased the dose of proton pump inhibitors or underwent fundoplication after the pH test. Outcome was positive in 77% of non-erosive reflux disease vs 43% of functional heartburn patients ( P < 0.05). Conclusions One-third of patients classified as functional heartburn at 24-hour pH-monitoring can be re-classified as non-erosive reflux disease after a more prolonged pH recording period. This observation has a positive impact on patients’ management.

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Section: Discussionmentioning

confidence: 59%

Inconsistency in the Diagnosis of Functional Heartburn: Usefulness of Prolonged Wireless pH Monitoring in Patients With Proton Pump Inhibitor Refractory Gastroesophageal Reflux Disease

Penagini

Sweis

Mauro

et al. 2015

J Neurogastroenterol Motil

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“…15 These studies have led to the consensus that oesophageal acid exposure decreases baseline impedance and that baseline impedance is a marker of oesophageal mucosal integrity. 13,16,17 In some patients with typical symptoms and signs of EoO, PPI seems to reduce inflammation en symptoms, and it partially restores the mucosal integrity. 21 These patients are now diagnosed with proton pump inhibitorresponsive oesophageal eosinophilia (PPI-ROE), although differences between PPI-ROE patients and EoO patients are currently unclear.…”

Section: Discussionmentioning

confidence: 99%

“…15 Together, these studies have led to the conclusion that oesophageal acid exposure decreases baseline impedance and that baseline impedance is a marker of oesophageal mucosal integrity. 13,16,17 Several authors have suggested that the oesophageal mucosal integrity is impaired in patients with EoO, in line with other allergic diseases such as atopic dermatitis and asthma. 5,6 We hypothesized that oesophageal baseline impedance is decreased in non-treated EoO patients.…”

Section: Introductionmentioning

confidence: 99%

Oesophageal baseline impedance values are decreased in patients with eosinophilic oesophagitis

et al. 2013

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Background: Gastro-oesophageal reflux has been suggested to play a role in eosinophilic oesophagitis (EoO). Oesophageal acid exposure decreases baseline intraluminal impedance, a marker of mucosal integrity, in patients with gastro-oesophageal reflux disease (GORD). Objectives: The aim of this study was to assess oesophageal baseline impedance levels in EoO patients and to investigate their relationship with oesophageal acid exposure. Methods: Ambulatory 24-h pH-impedance monitoring was performed in 11 EoO patients and in 11 healthy controls with matched oesophageal acid exposure. We assessed baseline impedance levels in the distal, mid-, and proximal oesophageal impedance channels.

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“…In fact, a large body of work shows that transmucosal potential difference and baseline electrical impedance of esophageal mucosa (markers of mucosa integrity) is lower in patients with symptoms of heartburn (erosive disease and non-erosive reflux disease), as compared to normal subjects. 19 Once in the mucosa and submucosa, proton/H + comes in contact with nociceptive nerve endings to induce heartburn and chest pain. If the above hypothesis were to be accurate, injection of hydrogen ions directly into the mucosa/submucosa should have caused heartburn/ chest pain, which was not observed in our study.…”

Section: Discussionmentioning

confidence: 99%

Esophageal Submucosal Injection of Capsaicin but Not Acid Induces Symptoms in Normal Subjects

Lee

Korsapati

Bhalla

et al. 2016

J Neurogastroenterol Motil

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Background/AimsTransient receptor potential vanilloid-1 (TRPV1) is a candidate for mediating acid-induced symptoms in the esophagus. We conducted studies to determine if the presence of acid in the mucosa/submucosa and direct activation of TRPV1 by capsaicin elicited symptoms in normal healthy subjects. We also studied the presence of TRPV1 receptors in the esophagus. MethodsUnsedated endoscopy was performed on healthy subjects with no symptoms. Using a sclerotherapy needle, normal saline (pH 2.0-7.5) was injected into the mucosa/submucosa, 5 cm above the Z line. In a separate group of healthy subjects, injection of capsaicin and vehicle was also studied. Quality of symptoms was reported using the McGill Pain Questionnaire, and symptom intensity using the visual analogue scale (VAS). Immunohistochemistry was performed on 8 surgical esophagus specimens using TRPV1 antibody. ResultsAcid injection either did not elicit or elicited mild symptoms in subjects at all pH solutions. Capsaicin but not the vehicle elicited severe heartburn/chest pain in all subjects. Mean VAS for capsaicin was 91 ± 3 and symptoms lasted for 25 ± 1 minutes. Immunohistochemistry revealed a linear TRPV1 staining pattern between the epithelial layer and the submucosa that extended into the papillae. Eighty-five percent of papillae stained positive for TRPV1 with a mean 1.1 positive papillae per high-powered field. ConclusionsThe mechanism of acid-induced heartburn and chest pain is not the simple interaction of hydrogen ions with afferents located in the esophageal mucosa and submucosa. TRPV1 receptors are present in the lamina propria and their activation induces heartburn and chest pain.

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In vivo evaluation of acid-induced changes in oesophageal mucosa integrity and sensitivity in non-erosive reflux disease

Abstract: Impaired mucosal integrity might be the consequence of repeated reflux episodes with slow recovery. Mucosal integrity, recovery capacity and symptom perception are linked. Low basal impedance and slow recovery after acid challenge are associated with increased acid sensitivity.

Cited by 113 publications

References 28 publications

Inconsistency in the Diagnosis of Functional Heartburn: Usefulness of Prolonged Wireless pH Monitoring in Patients With Proton Pump Inhibitor Refractory Gastroesophageal Reflux Disease

Inconsistency in the Diagnosis of Functional Heartburn: Usefulness of Prolonged Wireless pH Monitoring in Patients With Proton Pump Inhibitor Refractory Gastroesophageal Reflux Disease

Oesophageal baseline impedance values are decreased in patients with eosinophilic oesophagitis

Esophageal Submucosal Injection of Capsaicin but Not Acid Induces Symptoms in Normal Subjects

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