Functional Heartburn Patients Research Articles

Tu1088 Distal and Proximal Esophageal Impedance Basal Values in Patients With Non-Erosive Reflux Disease and Functional Heartburn

Background and aim: Several studies have shown that proximal extent of reflux episodes plays an important role in gastro-esophageal reflux symptom perception. The relative hypersensitivity of the proximal esophagus is most evident in patients with non-erosive reflux disease (NERD). Recent studies demonstrated that low distal basal impedance values may reflect impaired mucosal integrity and increased acid sensitivity. The aim was to compare distal and proximal basal impedance values in patients with NERD and functional heartburn (FH). Methods: According to impedance and pH (MII-pH) monitoring off-therapy, we selected patients with NERD (i.e. pathological acid exposure time, AET) and FH (i.e. normal AET and reflux number; negative symptom association). FH patients did not show any symptom relief after acid suppression therapy. For each patient, we evaluated basal impedance values at the distal (3 cm) and proximal (17 cm) channel, during the overnight rest, at three different times: 1, 2, 3 am. Results: Male/female ratio was 23/23 in NERD and 13/33 in FH patients. Mean age was 52.3±13.2 in NERD and 49.2±11.3 in FH. Mean AET was higher in NERD (6.1%±3.8%) than in FH (0.6%±0.7%) (p<0.05). NERD group recorded higher total reflux number (67.8±18.2) than FH group (23.7±9.4) (p<0.05). Basal impedance values were significantly (p<0.05) lower in NERD than in FH, both at the distal (1294.3±529.9 Ohm vs 3502.1±809.2 Ohm) and proximal (3480.7 ±1322.6 Ohm vs 4344.9±976.2 Ohm) channels. Distal basal values were significantly lower than proximal basal values, both in NERD and FH group (p<0.05). Moreover, in NERD group, 24/46 patients (52.2%) had an abnormal number of proximal refluxes. These NERD patients with pathological proximal refluxes did not show lower basal impedance values than NERD patients with normal number of proximal refluxes even if distal (1226.7±453 vs 1243.1±497.1; P=0.5239) or proximal channels (2670.8±1163.4 vs 2849.2±1434.2; p=0.5046) were compared. Summary and conclusion: Patients with NERD showed lower basal impedance values both at the distal and proximal esophagus. Consistently with the concept that low basal impedance may reflect impaired mucosal integrity, our results might be helpful to better investigate the pathophysiological role of proximal refluxes.

Tu1089 Evaluation of Sleep Disruptions by Means of Impedance-pH Monitoring in Patients With NERD

Background and aim: Several studies have shown that proximal extent of reflux episodes plays an important role in gastro-esophageal reflux symptom perception. The relative hypersensitivity of the proximal esophagus is most evident in patients with non-erosive reflux disease (NERD). Recent studies demonstrated that low distal basal impedance values may reflect impaired mucosal integrity and increased acid sensitivity. The aim was to compare distal and proximal basal impedance values in patients with NERD and functional heartburn (FH). Methods: According to impedance and pH (MII-pH) monitoring off-therapy, we selected patients with NERD (i.e. pathological acid exposure time, AET) and FH (i.e. normal AET and reflux number; negative symptom association). FH patients did not show any symptom relief after acid suppression therapy. For each patient, we evaluated basal impedance values at the distal (3 cm) and proximal (17 cm) channel, during the overnight rest, at three different times: 1, 2, 3 am. Results: Male/female ratio was 23/23 in NERD and 13/33 in FH patients. Mean age was 52.3±13.2 in NERD and 49.2±11.3 in FH. Mean AET was higher in NERD (6.1%±3.8%) than in FH (0.6%±0.7%) (p<0.05). NERD group recorded higher total reflux number (67.8±18.2) than FH group (23.7±9.4) (p<0.05). Basal impedance values were significantly (p<0.05) lower in NERD than in FH, both at the distal (1294.3±529.9 Ohm vs 3502.1±809.2 Ohm) and proximal (3480.7 ±1322.6 Ohm vs 4344.9±976.2 Ohm) channels. Distal basal values were significantly lower than proximal basal values, both in NERD and FH group (p<0.05). Moreover, in NERD group, 24/46 patients (52.2%) had an abnormal number of proximal refluxes. These NERD patients with pathological proximal refluxes did not show lower basal impedance values than NERD patients with normal number of proximal refluxes even if distal (1226.7±453 vs 1243.1±497.1; P=0.5239) or proximal channels (2670.8±1163.4 vs 2849.2±1434.2; p=0.5046) were compared. Summary and conclusion: Patients with NERD showed lower basal impedance values both at the distal and proximal esophagus. Consistently with the concept that low basal impedance may reflect impaired mucosal integrity, our results might be helpful to better investigate the pathophysiological role of proximal refluxes.

664 Newly Developed Bioelectrical Admittance Measurement Distinguishes Patients With Non-Erosive Reflux Disease From Those With Functional Heartburn

Background & Aims: Almost 70% of patients complaining of heartburn have no macroscopic evidence of esophageal mucosal damage, and are termed as having either non-erosive reflux disease (NERD) or functional heartburn (FH). Microscopic esophagitis (ME) is common in patients with NERD, and the succeeding changes of dilation of intercellular spaces (DIS) has been regarded as the potential main mechanism of symptom generation. It has been reported that edema and inflammation as well as DIS in the tissue are related to the decreasing electrical impedance. The aim of this study was to validate our newly developed bioelectrical admittance method (BAM) as a measure of admittance (numerically equal to the reciprocal of the impedance) of esophageal wall and investigate the differences in bioelectrical admittance between NERD and FH patients. Methods: The BAM was performed at the distal esophagus during upper endoscopy in consecutive 25 patients with heartburn. In each patient, three specimens were taken from the same lesion where the BAM was performed. The histological alterations and gene expression levels of mediators of inflammation and tight junction proteins such as claudin1, claudin4, ZO-1 and occludin were evaluated, and DIS was also evaluated by an electron microscope. The correlation between bioelectrical admittance and tissue resistance measured by an Ussing chamber was investigated for 5 subjects. All patients were prescribed double doses of proton pump inhibitor (PPI) for 2 weeks, and after that patients were divided into 2 groups: good response to PPI (Group A) and poor response to PPI (Group B). Results: There were17 patients in the Group A and 18 patients in the Group B. Symptom severity of heartburn was not significantly different between the two groups. The histopathological findings showed that the prevalence of ME was significantly higher (p<0.05) in the Group A (65%) than in the Group B (10%). DIS also showed similar rates of prevalence. There were differences in expression levels of tight junction proteins between the two groups. Furthermore, patients in the Group A were characterized by the increase in the mRNA expression level of TNFα. There was a significant negative correlation between bioelectrical admittance and tissue resistance evaluated by an Ussing chamber (p<0.05). Patients in the Group A displayed significant higher bioelectrical admittance than those in the Group B (p<0.05), and a significant association between the severity of lowgrade inflammation and the extent of increased bioelectrical admittance of esophageal wall (r=0.45, p<0.05). Conclusions: The BAM is a new method to evaluate esophageal mucosal integrity during upper endoscopy. The low-grade inflammation on esophageal mucosa and electrical conductivity are good clinical markers for the assessment of the responsiveness to PPI in patients with heartburn.

Sa1185 Dysbiosis of the Mucosa-Adherent Microbiome in Patients With Irritable Bowel Syndrome

Background: Functional Gastrointestinal Disorders (FGIDs) are identified by the dominant presenting symptoms: functional heartburn (FH), irritable bowel syndrome (IBS), dyspepsia, etc. This nomenclature assumes an organ-specific origin of symptoms rather than symptoms associated with a common pathophysiology such as visceral hypersensitivity. The symptoms reported in most FGIDs overlap more than one gastrointestinal (GI) organ. FH patients report abdominal cramping, bloating and nausea with their FH symptoms. This study tested the primary hypothesis that there is a correlation of MPT in the esophagus and rectum in FH patients. Secondary aims evaluated correlations with IPT and PT. Methods:. This study explored objective sensory endpoints of initial perception threshold (IPT), pain threshold (PT), and maximum pain threshold (MPT) in the esophagus and rectum of FH subjects to determine whether visceral hypersensitivity is a generalized or organ specific observation Fourteen women with FH participated in this study. Each subject underwent a training sensory study protocol session including step volume and pressure ramp balloon barostat distention of the esophagus and rectum. A data collection visit occurred within 7-14 days to collect data on balloon volume and pressure measurements at IPT, PT, and MPT with esophageal and rectal barostat distention. The relationship of sensation and pain to volume, pressure, and compliance was analyzed. Results: The correlation between esophageal and rectal IPT balloon volume scores was highly and significantly correlated (r = 0.61, p = 0.02). The correlation between esophageal and rectal PT balloon volume scores was highly and significantly correlated (r = 0.6, p = 0.02). The correlation between esophageal and rectal MPT balloon volume scores was not correlated (r = 0.35, p = 0.26). In contrast to volume, the pressure endpoints were not significantly correlated. Conclusions: 1. In this study, there was weak correlation for the relationship of rectal and esophageal volume scores at MPT (Primary Aim). Findings revealed a strong positive correlation for the relationship of rectal and esophageal volume and pressure scores to IPT and PT (Secondary Aims). The lack of MPT correlation may provide insight into the organ specific stratification of FGIDs through identification of the most sensitive organ. 2. In this study, volume was superior to pressure in assessing changes in visceral sensitivity in FGID patients. 3. The correlation of visceral sensitivity in the esophagus and rectum in patients with FH supports the hypothesis that visceral sensory changes in FGIDs are not organ specific. 4. Visceral hypersensitivity throughout the GI tract may explain the overlapping symptoms in FGID patients suggesting visceral sensitivity may occur in two separate areas of the GI tract simultaneously.

Sa1184 A Comparison of Rectal and Esophageal Sensitivity in Women With Functional Heartburn

Background: Functional Gastrointestinal Disorders (FGIDs) are identified by the dominant presenting symptoms: functional heartburn (FH), irritable bowel syndrome (IBS), dyspepsia, etc. This nomenclature assumes an organ-specific origin of symptoms rather than symptoms associated with a common pathophysiology such as visceral hypersensitivity. The symptoms reported in most FGIDs overlap more than one gastrointestinal (GI) organ. FH patients report abdominal cramping, bloating and nausea with their FH symptoms. This study tested the primary hypothesis that there is a correlation of MPT in the esophagus and rectum in FH patients. Secondary aims evaluated correlations with IPT and PT. Methods:. This study explored objective sensory endpoints of initial perception threshold (IPT), pain threshold (PT), and maximum pain threshold (MPT) in the esophagus and rectum of FH subjects to determine whether visceral hypersensitivity is a generalized or organ specific observation Fourteen women with FH participated in this study. Each subject underwent a training sensory study protocol session including step volume and pressure ramp balloon barostat distention of the esophagus and rectum. A data collection visit occurred within 7-14 days to collect data on balloon volume and pressure measurements at IPT, PT, and MPT with esophageal and rectal barostat distention. The relationship of sensation and pain to volume, pressure, and compliance was analyzed. Results: The correlation between esophageal and rectal IPT balloon volume scores was highly and significantly correlated (r = 0.61, p = 0.02). The correlation between esophageal and rectal PT balloon volume scores was highly and significantly correlated (r = 0.6, p = 0.02). The correlation between esophageal and rectal MPT balloon volume scores was not correlated (r = 0.35, p = 0.26). In contrast to volume, the pressure endpoints were not significantly correlated. Conclusions: 1. In this study, there was weak correlation for the relationship of rectal and esophageal volume scores at MPT (Primary Aim). Findings revealed a strong positive correlation for the relationship of rectal and esophageal volume and pressure scores to IPT and PT (Secondary Aims). The lack of MPT correlation may provide insight into the organ specific stratification of FGIDs through identification of the most sensitive organ. 2. In this study, volume was superior to pressure in assessing changes in visceral sensitivity in FGID patients. 3. The correlation of visceral sensitivity in the esophagus and rectum in patients with FH supports the hypothesis that visceral sensory changes in FGIDs are not organ specific. 4. Visceral hypersensitivity throughout the GI tract may explain the overlapping symptoms in FGID patients suggesting visceral sensitivity may occur in two separate areas of the GI tract simultaneously.

PTU-163 Proximal Oesophageal Functional Mucosal Integrity during Distal Oesophageal Acidification in Patients with Nerd and FH

IntroductionAlthough macroscopically normal, the oesophageal mucosa in patients with non-erosive reflux disease (NERD) displays epithelial dilated intercellular spaces (DIS). Such loss of barrier integrity is thought to be important in...

Functional heartburn

Patients with heartburn and normal upper gastrointestinal endoscopy, normal oesophageal acid exposure, no symptom-reflux association and who fail to respond to a proton-pump inhibitor are classified as having functional heartburn (FH). This study aimed (i) to characterize the symptoms and functional abnormalities of patients with FH and (ii) to describe their clinical outcome. Among all patients referred for 24 h multichannel intraluminal impedance-pH (MII-pH), patients with FH were identified. The clinical characteristics and high-resolution oesophageal pressure topography recordings of FH patients were analyzed at the time of the 24-h MII-pH test. A symptom-related and health-related quality-of-life questionnaire was then sent to FH patients to assess the long-term outcome. Forty patients fulfilled the criteria for FH, representing 8.5% of the referred population. Twenty-two months after initial testing, 66% of patients still suffered from heartburn. The rate of mixed reflux (liquid/gas) was higher in patients with persisting heartburn at the final evaluation (63 vs. 50%, P=0.04). Sixty-six per cent of patients had one or more manometric abnormalities. Acid clearance time in MII-pH was significantly higher in patients with weak peristalsis than patients with normal peristalsis (60 ± 45 vs. 31 ± 19 s, P=0.03). A high rate of mixed reflux and/or a manometric abnormality were associated with a higher risk of persistent heartburn. FH is a chronic disorder with persisting symptoms in two-thirds of patients. An increased rate of mixed reflux and/or the presence of manometric abnormalities are associated with a higher risk of persisting symptoms and may help to identify the population with unmet therapeutic needs.

Acid Sensitization of Esophageal Mucosal Afferents

Sensitization of esophageal chemoreceptors, either directly by intermittent acid exposure or indirectly through esophagitis-associated inflammatory mediators, is likely to be the mechanism underlying the perception of heartburn. To compare basal esophageal sensitivity with electrical stimulation and acid, and to compare the degree of acid-induced sensitization in controls and in patient groups across the entire spectrum of gastroesophageal reflux disease: erosive oesophagitis (EO), nonerosive reflux disease (NERD), and functional heartburn (FH). Esophageal sensory and pain thresholds to electrical stimulation were measured before, 30, and 60 minutes after an intraesophageal infusion of saline or HCl. Patients received a 30-minute infusion of 0.15 M HCl and controls were randomized to receive either HCl (n = 11) or saline (n = 10). After electrical sensory threshold testing, participants received another 30-minute infusion of HCl to determine whether sensitivity to acid is increased by prior acid exposure All patient groups had higher basal sensory thresholds than healthy controls (controls, 13 ± 1.4 mA; FH, 20 ± 5.1 mA; NERD, 21 ± 5.1 mA; EO, 23 ± 5.4 mA; P < 0.05). Acute esophageal acid exposure reduced sensory thresholds to electrical stimulation in FH and NERD patients (P < 0.05). The level of acid sensitivity during the first HCl infusion was comparable between all patient groups and controls. The secondary infusion caused increased discomfort in all participants (P < 0.01). This acid-induced sensitization to HCl was significantly elevated in the patient groups ( P < 0.05). (1) Esophageal acid infusion sensitizes it to subsequent electrical and chemical stimulation. (2) The acid-related sensitization is greater in gastroesophageal reflux disease than in controls and may influence in part symptom perception in this population. (3) Acid-related sensitization within the gastroesophageal reflux disease population is not dependant on mucosal inflammation.

Esophageal Dysmotility Increases with the Severity of Gastroesophageal Reflux Disease: A Study Using High Resolution Manometry and the Revised Chicago Classification Criteria

Purpose: Past studies utilizing the conventional manometric definition of Ineffective Esophageal Motility have yielded conflicting results regarding the prevalence of dysmotility among GERD subgroups. Recently, the International High Resolution Manometry (HRM) Working Group issued new definitions for peristaltic function using the Chicago Classification (CC). The purpose of this study was to apply the new CC criteria to determine the prevalence of dysmotility among patients with Erosive Esophagitis (EE), Non-Erosive Reflux Disease (NERD) and Functional Heartburn (FH). Methods: A retrospective review of 150 patients who underwent HRM for GERD symptoms was performed. Patients were divided into 3 groups based upon endoscopic and esophageal pH or impedance testing: 1) EE (Esophagitis on EGD) (n=50), 2) NERD (normal EGD and pathological acid exposure on pH Testing or > 48 reflux events on impedance) (n=63), 3) FH (normal EGD, normal pH or impedance) (n=37). HRM studies were then characterized using the CC for peristaltic abnormalities and Esophagogastric Junction (EGJ) types. Results: The most common pattern among FH patients was normal motility (68%) which was higher than in the EE (12%, p<0.0001) and NERD (37%, p=0.004) groups. The FH group could be distinguished from NERD patients with lower rates of Weak Peristalsis with Large Peristaltic Defects (Figure 1). Comparisons between FH and EE yielded lower rates for Absent Peristalsis (0% vs 14%, p=0.018), Frequent Failed Peristalsis (0% vs 14%, p=0.018) and Weak Peristalsis with Large Peristaltic Defects (14% vs 42%, p=0.005). EE patients could be distinguished from the NERD group based upon higher rates of Absent Peristalsis (Figure 1). EGJ type 2 (1-2 cm separation between the crural diaphragm and lower esophageal sphincter) was more common in EE (30%) and NERD (29%) than in FH (11%) (p=0.038, p=0.047). EGJ type 3 (> 2 cm separation) also differentiated EE (20%) patients from FH (3%) (p=0.021).Figure: Prevalence of motility patterns among gerd subtypes using the revised chicago classification for high resolution esophageal manometry.Conclusion: HRM patterns for peristaltic dysfunction and the EGJ are different among GERD subgroups. Esophageal dysmotility characterized by the new Chicago Classification guidelines increases with the severity of esophageal acid exposure.

Microscopic esophagitis distinguishes patients with non-erosive reflux disease from those with functional heartburn

Microscopic esophagitis (ME) is common in patients with non-erosive reflux disease (NERD), and dilation of intercellular spaces (DIS) has been regarded as the potential main mechanism of symptom generation. We aimed to compare these histological abnormalities in healthy volunteers (HVs) and patients with erosive esophagitis (EE), NERD, and functional heartburn (FH). Consecutive patients with heartburn prospectively underwent upper endoscopy and impedance-pH off-therapy. Twenty EE patients and fifty-seven endoscopy-negative patients (NERD), subclassified as 22 with pH-POS (positive for abnormal acid exposure), 20 with hypersensitive esophagus (HE; normal acid/symptom association probability [SAP]+ or symptom index [SI]+), and 15 with FH (normal acid/SAP-/SI-/ proton pump inhibitor [PPI] test-), were enrolled. Twenty HVs were also included. In each patient/control, multiple specimens (n=5) were taken from the distal esophagus and histological alterations were evaluated. ME was diagnosed when the global histological score was >0.35. The prevalence of ME was higher (p<0.0001) in EE (95%), pH-POS (77%), and HE (65%) NERD patients than in FH patients (13%) and HVs (15%). Also, basal cell hyperplasia (p<0.0023), DIS (p<0.0001), and papillae elongation (p<0.0002) showed similar rates of prevalence in the above populations (p<0.0001). ME, including each histological lesion, had similar low frequencies in FH and HVs (p=0.9990). Considering the histological abnormalities together, they permitted us to clearly differentiate EE and NERD from FH and HVs (p<0.0001 and p<0.0001, respectively). The lack of ME in the esophageal distal biopsies of FH patients indicates a limited role of these histological abnormalities in symptom generation in them. ME can be considered as an accurate and reliable diagnostic marker for distinguishing FH patients from GERD patients and has the potential to be used to guide the correct therapy.

Impedance-pH reflux patterns can differentiate non-erosive reflux disease from functional heartburn patients

Symptom association is important to distinguish non-erosive reflux disease [NERD; abnormal oesophageal acid exposure time (AET) and/or positive symptom association] from functional heartburn (FH; normal AET and negative symptom association). Asymptomatic patients during reflux monitoring are challenging as symptom association cannot be assessed. To evaluate whether impedance-pH reflux patterns are useful to differentiate NERD from FH. Endoscopy-negative reflux patients underwent impedance-pH off-therapy. Oesophageal AET, characteristics of reflux episodes and symptom association probability (SAP) were measured. Twenty patients asymptomatic during the first test repeated a second examination. Of 329 patients, 130 (40%) were pH-POS, 120 (36%) pH-NEG/SAP+ (hypersensitive oesophagus=HO) and 79 (24%) pH-NEG/SAP- (FH). Total and acid reflux episodes were significantly higher (p<0.01) in pH-POS compared to pH-NEG/SAP+, pH-NEG/SAP- and healthy volunteers (HVs). Patients pH-NEG/SAP+ had a significantly increased number of weakly acidic reflux episodes compared to pH-POS, pH-NEG/SAP- and HVs (p<0.01). The rate of proximal reflux episodes in pH-POS (50%) and pH-NEG/SAP+ (47%) was higher (p<0.01) than in pH-NEG/SAP- (33%) and HVs (33%). Measuring AET, number of reflux episodes and percentage of proximal reflux events permits to identify FH in 70% of cases and HO in 80% of cases who repeated the examination. In patients with normal AET and SAP+, increased number of weakly acidic reflux and higher rate of proximal reflux are the main discriminant features. There is large overlap between FH and HVs. These differences can be of help in diagnosing patients with normal oesophageal acid exposure who fail to have symptoms during MII-pH testing.

The added value of impedance-pH monitoring to Rome III criteria in distinguishing functional heartburn from non-erosive reflux disease

Introduction Functional heartburn is defined by Rome III criteria as an endoscopy-negative condition with normal oesophageal acid exposure time, negative symptom association to acid reflux and unsatisfactory response to proton pump inhibitors. These criteria underestimated the role of non-acid reflux. Aim To assess the contribution of impedance-pH with symptom association probability (SAP) analysis in identifying endoscopy-negative patients with reflux disease and separating them from functional heartburn. Methods Consecutive endoscopy-negative patients treated with proton pump inhibitors ( n = 219) undergoing impedance-pH monitoring off-therapy were analysed. Distal acid exposure time, reflux episodes, SAP and symptomatic response to proton pump inhibitors were measured. Results Based on impedance-pH/SAP, 67 (31%) patients were pH+/SAP+, 6 (2%) pH+/SAP−, 83 (38%) hypersensitive oesophagus and 63 (29%) functional heartburn. According to pH-metry alone/response to proton pump inhibitors, 62 (28%) were pH+/SAP+, 11 (5%) pH+/SAP−, 61 (28%) hypersensitive oesophagus and 85 (39%) functional heartburn. In the normal-acid exposure population the contribution of impedance-pH/SAP compared to pH-metry alone/response to proton pump inhibitors in identifying patients with reflux disease and functional heartburn resulted to be 10%. In patients with abnormal-acid exposure, the contribution of impedance-pH/SAP increased by 3%. Conclusion Comparing impedance-pH testing with pH-metry alone plus the response to proton pump inhibitor therapy demonstrated that the latter ones cause underestimation of reflux disease patients and overestimation of functional heartburn patients.

The proton pump inhibitor test and the diagnosis of gastroesophageal reflux disease

There continues to be significant controversy related to diagnostic testing for gastroesophageal reflux disease (GERD). Symptoms of GERD may be associated with physiologic esophageal acid exposure measured by intraesophageal pH monitoring or pH-impedance monitoring, and a significant percentage of patients with abnormal esophageal acid (or weak acid) exposure have no or minimal clinical symptoms of reflux. On the other hand, endoscopic lesions are only present in a minority of GERD patients. In clinical practice, presumptive diagnosis of GERD is reasonably assumed by the substantial reduction or elimination of suspected reflux symptoms during the therapeutic trial of acid reduction therapy, the so-called proton pump inhibitor (PPI) test. We aimed to assess the optimal cutoff value and duration of this test in GERD patients with and without esophagitis. We conducted a prospective study of 544 patients, endoscopically investigated and treated for 2 weeks with PPIs at double dose, and for an additional 3 months at standard dose. The status of the patient at the end of the study was used as an independent diagnostic standard. We found esophagitis present in 55.8% and absent in 44.2% of patients (corresponding to a diagnosis of nonerosive reflux disease [NERD]). The test was positive in 89.7–97.8% of the patients according to the cutoff or duration of the test used. The sensitivity of the PPI test was excellent, ranging from 95.5 to 98.8%, whereas the specificity was poor, not exceeding 36.3%. Erosive esophagitis patients responded more favorably to the PPI test and subsequent PPI therapy compared with NERD patients. In conclusion, the PPI test is a sensitive but less specific test. Its optimal duration is 1 week, and the optimal cutoff value is a decrease of heartburn score of more than 75%. NERD patients respond less satisfactorily to PPIs, even when functional heartburn patients are excluded and only ‘true’ NERD patients are considered.

Quantitative Assessment and Characterization of Visceral Hyperalgesia Evoked by Esophageal Balloon Distention and Acid Perfusion in Patients With Functional Heartburn, Nonerosive Reflux Disease, and Erosive Esophagitis

The role of esophageal hypersensitivity in functional heartburn (FH) with negative pH test, negative symptom index, and the proton pump inhibitor (PPI) failure has not been established. The aim of this study was to investigate the characterization of visceral hyperalgesia evoked by esophageal balloon distention and acid perfusion in patients with FH, nonerosive reflux disease, and erosive esophagitis and further characterize the pathophysiologic mechanism of FH. A total of 21 FH patients (with esophageal acid exposure <3.1% and a symptom index<50% and nonresponse to a therapeutic trial with proton pump inhibitors, 25 Nonerosive reflux disease (NERD) patients (with esophageal acid exposure>4%), 23 erosive esophagitis (EE) patients (LA grade B to D), and 18 healthy controls were recruited in the study. Mechanosensitivity including the initial perception threshold (IPT) and pain threshold (PT) was evaluated by using a Barostat with a double-random staircase distension protocol. Chemosensitivity was graded along a visual analog scale after perfusion of saline and 0.1 N HCl. The baseline IPTs and PTs were all lower in patients with FH, NERD, and EE than in the controls (all P<0.01). In addition, the baseline PT in FH patients was significantly lower than those in NERD (P=0.015) and EE patients (P<0.001). After acid perfusion, the mean symptom intensity scores were significantly greater in patients with FH, NERD, and EE than those in the controls (all P<0.001). The postacid perfusion IPTs in patients with FH, NERD, and EE were all significantly lower than the corresponding baseline values (all P<0.01). The PTs in FH (P=0.026) and EE patients (P<0.001) were significantly lower than the corresponding baseline values. Moreover, the postacid perfusion PT was significantly lower in FH patients than in NERD patients (P<0.001). FH patients are more sensitive to mechanical or chemical stimuli than NERD patients. Sensitization of esophageal acid-sensitive chemoreceptors may exert a significant influence on the pressure-sensitive mechanoreceptors, and there is the cooperative interaction in the process of esophageal visceral hyperalgesia.

The Overlap Between GERD and Functional Bowel Disorders - When East Meets Rome

The Overlap Between GERD and Functional Bowel Disorders - When East Meets Rome

T1680 Functional Heartburn Patients are Characterized by Increased Frequency and Perception of Liquid-Gas and Proximal Reflux

s / Digestive and Liver Disease 42S (2010) S61–S192 S105 can increase gastrin levels. More recently also CgA concentrations have been found elevated during PPI therapy. A possible use of this parameter in evaluating ECL hyperplasia, within this context, has been suggested. This study was undertaken to investigate the relationship between gastrin and CgA levels and intragastric pH during acid suppressive therapy to evaluate the behaviour of serum gastrin and CgA in patients under prolonged PPI treatment. Material and methods: 24-hour gastric-oesophageal pH-metry was performed in 25 patients with persistent reflux symptoms after at least 3 months of PPI treatment. Blood samples for gastrin and CgA were collected before starting the procedure and assessed by radioimmunoassay. Gastrin and CgA were also evaluated in 50 patients under long term PPI therapy (more than 1 year) for GERD. Repeated measurements on/off therapy were available in 10 cases. Results: Increased gastrin and CgA values were found in 13 (58%) and in 19 (76%) patients undergoing ph-metry respectively. 6 patients with elevated CgA displayed normal gastrin levels. No correlation was evidentiated between G (r= 0.24; p=0.25) and CgA (r= 0.102; p=0.63) concentrations and the degree of inhibition of gastric secretion expressed as % of time with gastric pH over 4 during 24-hour. In patients on long term treatment, elevated G and CgA levels were detected in 34 (68%) and 39 (78%) cases respectively (range 132-1000 pg/ml for G and 122-1250 ng/ml for CgA). Within patients with hypergastrinemia 4 presented normal CgA; within those with increased CgA 9 had normal gastrin. In this latter group PPI withdrawal, when performed, resulted in CgA normalization; furthermore, of the 3 patients who underwent endoscopy, 2 showed ECL hyperplasia at histology. Conclusions: According to our data, serum gastrin and CgA concentrations during PPI therapy are highly variable within patients and not related to the degree of suppression of gastric secretion. Serum CgA seems to pick up better than gastrin patients at higher risk of ECL hyperplasia during prolonged PPI treatment. # A. Oesophagus 1. GERD

Power Spectral Analysis of the Sleep Electroencephalogram in Heartburn Patients With or Without Gastroesophageal Reflux Disease

Determine the feasibility of using power spectrum of the sleep electroencephalogram (EEG) as a more sensitive tool than sleep architecture to evaluate the relationship between gastroesophageal reflux disease (GERD) and sleep. GERD has been shown to adversely affect subjective sleep reports but not necessarily objective sleep parameters. Data were prospectively collected from symptomatic patients with heartburn. All symptomatic patients underwent upper endoscopy. Patients without erosive esophagitis underwent pH testing. Sleep was polygraphically recorded in the laboratory. Spectral analysis was performed to determine the power spectrum in 4 bandwidths: delta (0.8 to 4.0 Hz), theta (4.1 to 8.0 Hz), alpha (8.1 to 13.0 Hz), and beta (13.1 to 20.0 Hz). Eleven heartburn patients were included in the GERD group (erosive esophagitis) and 6 heartburn patients in the functional heartburn group (negative endoscopy, pH test, response to proton pump inhibitors). The GERD patients had evidence of lower average delta-power than functional heartburn patients. Patients with GERD had greater overall alpha-power in the latter half of the night (3 hours after sleep onset) than functional heartburn patients. No significant differences were noted in conventional sleep stage summaries between the 2 groups. Among heartburn patients with GERD, EEG spectral power during sleep is shifted towards higher frequencies compared with heartburn patients without GERD despite similar sleep architecture. This feasibility study demonstrated that EEG spectral power during sleep might be the preferred tool to provide an objective analysis about the effect of GERD on sleep.

Comparison of Electron Microscopy vs. Light Microscopy for Diagnosing GERD in Patients with Refractory Heartburn

Purpose: In patients with ongoing heartburn despite acid suppression with PPIs, especially in the absence of endoscopic changes, the diagnosis of GERD is challenging and often requires prolonged reflux monitoring. Histological changes attributed to reflux in esophageal biopsies examined by light microscopy (LM) are suboptimal for diagnosing GERD. Dilation of intercellular space distance (ISD) in esophageal epithelium assessed by electron microscopy (EM) is emerging as a robust marker of GERD. Our aim was to compare the sensitivity and specificity of EM vs. LM for the diagnosis of GERD in patients with persistent heartburn despite PPI. Methods: Patients with persistent heartburn despite PPI BID underwent 24 hr-hr ambulatory impedance-pH (MII-pH), and endoscopy (EGD) with biopsies 5 cm above the Z line for analysis by EM and LM. Two schemes with different rigor used to diagnose GERD: “rigorous criteria” were esophagitis on EGD or abnormal MII-pH defined by increased esophageal acid exposure; “less rigorous criteria” added positive symptom index (>50% symptoms associated with reflux) to definition GERD. In both schemes, functional heartburn patients (FH) had normal EGD and MII-pH. Intercellular space distance (ISD) determined blindly by EM at 5,000 magnification using computer-assisted morphometry (Image J software). 10 ISD measurements taken in each of 10 micrographs, mean ISD was the average of 100 measurements. Upper limit of normal ISD was 0.68 μm (the 95th percentile ISD in ten healthy volunteers with normal pH-metry). Light microscopy evaluation performed by single, blinded gastrointestinal pathologist after routine hematoxylin and eosin staining, who provided a diagnosis of GERD based on rete papillae elongation or basal cell hyperplasia. The sensitivity and specificity of EM and LM for GERD were then compared. Results: Use of the more rigorous EGD/MII-pH criteria yielded 6 GERD and 16 FH patients; sensitivity and specificity were 83% and 88% for EM, 67% and of 44% for LM. The less rigorous criteria yielded 12 GERD and 10 FH patients; sensitivity and specificity were 58% and 100% for EM, 67% and 50% for LM. Specificity for GERD appears good for EM and poor for LM. Sensitivity is fair and comparable for EM and LM using less rigorous criteria for GERD, sensitivity is better for EM compared to LM when using more stringent criteria. Conclusion: Increased intercellular space distance measured by Electron Microscopy has good specificity and is thus very reliable (and superior to LM) for excluding GERD in patients with refractory heartburn, providing good accuracy for the diagnosis of functional heartburn. EM has good sensitivity, especially in patients with GERD diagnosed by more rigorous criteria.

Building a better mousetrap? Impedance measurement in gastroesophageal reflux disease

Building a better mousetrap? Impedance measurement in gastroesophageal reflux disease

Reflux profile of Chinese gastroesophageal reflux disease patients with combined multichannel intraluminal impedance‐pH monitoring

To investigate the reflux profile of Chinese gastroesophageal reflux disease (GERD) patients with the aid of combined multichannel intraluminal impedance-pH (MII-pH) monitoring technique. Consecutive patients presented with GERD symptoms were enrolled to erosive esophagitis (EE) group, non-erosive reflux disease (NERD) group and functional heartburn (FH) group after upper endoscopy, combined MII-pH monitoring and rabeprazole test. Another 20 healthy controls (HC) were recruited. Sixty-four GERD patients (EE:20, NERD:22, FH:22, HC:20) were enrolled. There were more episodes of liquid reflux and proximal reflux in EE and NERD groups than that in FH and HC groups (P < 0.05). Patients in FH and HC groups had higher proportion of mixed reflux (P = 0.000). The percentage of acid reflux in EE and NERD was much higher, while there was a higher percentage of weakly acidic reflux in FH and HC (P = 0.000). No significant difference was found in MII-pH parameters between groups with and without response to rabeprazole test except recumbent percentage time of esophageal pH value below 4 and episodes of proximal reflux. Erosive esophagitis and NERD patients had more liquid and proximal reflux episodes than FH patients and healthy controls. Acid and liquid reflux was predominant in the former two groups, while weakly acidic and mixed reflux was predominant in the latter two groups.