Multichannel Intraluminal impedance-pH Testing Research Articles

A prediction model of abnormal acid reflux in gastroesophageal reflux disease.

The measurement of esophageal acid exposure time (AET) using combined multichannel intraluminal impedance-pH (MII-pH) tests is the gold standard for diagnosing gastroesophageal reflux disease (GERD). However, this catheter-based 24-h test can cause considerable patient discomfort. Our aim is to identify factors affecting AET and to develop a scoring model for predicting AET abnormalities before conducting the MII-pH test. Of the 366 patients who underwent MII-pH test at two facilities in Japan and Vietnam, 255 patients who also had esophagogastroduodenoscopy and high-resolution manometry were included in this study. Logistic regression analysis was conducted using risk factors for AET>6% identified from a derivation cohort (n=109). A scoring system predicting AET>6% was then constructed and externally validated with a separate cohort (n=146). Three variables were derived from the prediction model: male gender, Hill grades III-IV, and weak mean distal contractile integrals. Based on these scores, patients were classified into low (0 point), intermediate (1-3 points), and high (4 points) risk groups. The probabilities of having an AET>6% were 6%, 34%, and 100% for these groups, respectively. A score of <1 excluded patients with abnormal AET, with a negative predictive value of 93.8% in the derivation cohort and 80.0% in the validation cohort. We derived and externally validated a prediction model for abnormal AET. This system could assist in guiding the appropriate treatment strategies for GERD.

Differences Between Patients with Heartburn Refractory to Vonoprazan and Those Refractory to Proton Pump Inhibitors

BackgroundVonoprazan, a potassium-competitive acid blocker, demonstrates more potent acid inhibition than proton pump inhibitors (PPIs). This study aimed to evaluate the effect of vonoprazan in patients with unproven gastroesophageal reflux disease (GERD) by comparing patients with vonoprazan-refractory heartburn with those with PPI-refractory heartburn.MethodsThis study included 104 consecutive patients with vonoprazan- or PPI-refractory heartburn (52 patients each), no erosive esophagitis on endoscopy and who underwent combined multichannel intraluminal impedance–pH (MII–pH) testing with vonoprazan/PPI discontinuation. Patients’ backgrounds, symptom scores from four questionnaires, MII–pH results and high-resolution manometry results were compared between the two groups.ResultsThe vonoprazan group demonstrated significantly higher GERD symptoms and scores of abdominal pain and diarrhea on the Gastrointestinal Symptom Rating Scale questionnaire. MII–pH results revealed that the vonoprazan group demonstrated 40.4%, 17.3%, and 42.3% and the PPIs group exhibited 26.9%, 17.3%, and 55.8% of abnormal acid reflux [true non-erosive reflux disease (NERD)], reflux hypersensitivity and functional heartburn, respectively. The vonoprazan group demonstrated higher true NERD rates but with no significant difference (p = 0.307). Among the vonoprazan group, eight patients with true NERD underwent another MII–pH test on vonoprazan, and all cases demonstrated normal acid exposure times (0.0% [0.0–0.3]).ConclusionPatients with unproven GERD with vonoprazan-refractory heartburn demonstrated more symptoms, including not only GERD symptoms but also functional dyspepsia and irritable bowel syndrome symptoms, than those with PPI-refractory heartburn.

The Dubai Definition and Diagnostic Criteria of Laryngopharyngeal Reflux: The IFOS Consensus.

The objective of this work was to gather an international consensus group to propose a global definition and diagnostic approach of laryngopharyngeal reflux (LPR) to guide primary care and specialist physicians in the management of LPR. Forty-eight international experts (otolaryngologists, gastroenterologists, surgeons, and physiologists) were included in a modified Delphi process to revise 48 statements about definition, clinical presentation, and diagnostic approaches to LPR. Three voting rounds determined a consensus statement to be acceptable when 80% of experts agreed with a rating of at least 8/10. Votes were anonymous and the analyses of voting rounds were performed by an independent statistician. After the third round, 79.2% of statements (N = 38/48) were approved. LPR was defined as a disease of the upper aerodigestive tract resulting from the direct and/or indirect effects of gastroduodenal content reflux, inducing morphological and/or neurological changes in the upper aerodigestive tract. LPR is associated with recognized non-specific laryngeal and extra-laryngeal symptoms and signs that can be evaluated with validated patient-reported outcome questionnaires and clinical instruments. The hypopharyngeal-esophageal multichannel intraluminal impedance-pH testing can suggest the diagnosis of LPR when there is >1 acid, weakly acid or nonacid hypopharyngeal reflux event in 24 h. A global consensus definition for LPR is presented to improve detection and diagnosis of the disease for otolaryngologists, pulmonologists, gastroenterologists, surgeons, and primary care practitioners. The approved statements are offered to improve collaborative research by adopting common and validated diagnostic approaches to LPR. 5 Laryngoscope, 134:1614-1624, 2024.

Novel Advanced Impedance Metrics on Impedance-pH Testing Predict Lung Function Decline in Idiopathic Pulmonary Fibrosis.

Gastroesophageal reflux has been associated with idiopathic pulmonary fibrosis (IPF). Mean nocturnal baseline impedance (MNBI) is a marker of esophageal mucosal integrity, whereas postreflux swallow-induced peristaltic wave (PSPW) index reflects esophageal chemical clearance. Both metrics offer novel ways to assess reflux burden on multichannel intraluminal impedance-pH testing (MII-pH), but their role in extraesophageal reflux remains unclear. We aimed to evaluate the relationship between these novel metrics and lung function decline in patients with IPF. Adults with IPF undergoing prelung transplant MII-pH were enrolled. All patients completed pulmonary function testing (PFT) at the time of MII-pH and at the 1-year follow-up. MNBI was calculated by averaging baseline impedance at three 10-minute intervals (1 AM/2 AM/3 AM). PSPW index was the proportion of all reflux episodes, followed by a peristaltic swallow within 30 seconds. Univariate (Student t-test/Pearson correlation) and multivariable (general linear regression) analyses were performed. One hundred twenty-five subjects (mean age = 61.7 years, 62% men) were included. Forced expiratory volume in one second and forced vital capacity declined more significantly over 12 months in subjects with lower distal MNBI, proximal MNBI, and PSPW index (all P < 0.05). On multivariable analyses adjusting for age, sex, proton pump inhibitor use, and baseline lung function, distal MNBI (β = -10.86, P = 0.024; β = -8.03, P = 0.045), proximal MNBI (β = -13.5, P = 0.0068; β = -9.80, P = 0.025), and PSPW index (β = -18.1, P = 0.010; β = -12.55, P = 0.050) remained predictive of greater forced expiratory volume in one second and forced vital capacity decline. Low distal MNBI, proximal MNBI, and PSPW index independently predicted more severe lung function decline over 1 year in patients with IPF. These impedance metrics may have prognostic value and support a role for reflux in IPF pathogenesis.

Devices for esophageal function testing.

Background and AimsEsophageal function testing is an integral component of the evaluation of refractory GERD and esophageal motility disorders. This review summarizes the current technologies available for esophageal function testing, including the functional luminal imaging probe (FLIP), high-resolution esophageal manometry (HRM), and multichannel intraluminal impedance (MII) and pH monitoring.MethodsWe performed a MEDLINE, PubMed, and MAUDE database literature search to identify pertinent clinical studies through March 2021 using the following key words: esophageal manometry, HRM, esophageal impedance, FLIP, MII, and esophageal pH testing. Technical data were gathered from traditional and web-based publications, proprietary publications, and informal communications with pertinent vendors. The report was drafted, reviewed, and edited by the American Society for Gastrointestinal Endoscopy Technology Committee and approved by the Governing Board of the American Society for Gastrointestinal Endoscopy.ResultsFLIP is a high-resolution impedance planimetry system used for pressure and dimension measurement in the esophagus, pylorus, and anal sphincter. FLIP provides complementary information to HRM for esophageal motility disorders, especially achalasia. The Chicago classification, based on HRM data, is a widely adopted algorithmic scheme used to diagnose esophageal motility disorders. MII detects intraluminal bolus movement and, combined with pH measurement or manometry, provides information on acid and non-acid gastroesophageal reflux and bolus transit in patients with refractory GERD and for preoperative evaluation for anti-reflux procedures.ConclusionsEsophageal function testing techniques (FLIP, HRM, and MII-pH) have diagnostic and prognostic value in the evaluation of esophageal motility disorders and refractory GERD. Newer technologies and classification systems have enabled an increased understanding of these diseases.

Impaired Proximal Esophageal Contractility Predicts Pharyngeal Reflux in Patients With Laryngopharyngeal Reflux Symptoms.

OBJECTIVES:The pathophysiology of laryngopharyngeal reflux (LPR) remains incompletely understood. Proximal esophageal motor dysfunction may impair bolus clearance, increasing the risk of pharyngeal refluxate exposure. We aimed to evaluate the association of proximal esophageal contractility with objective reflux metrics.METHODS:We evaluated adults with LPR symptoms undergoing high-resolution manometry (HRM) and combined hypopharyngeal-esophageal multichannel intraluminal impedance-pH testing at a tertiary center between March 2018 and August 2019. Routine parameters per Chicago classification were obtained on HRM. Proximal esophageal contractility was evaluated using proximal contractile integral (PCI), which quantifies contractile pressure >20 mm Hg for the region spanning the distal margin of the upper esophageal sphincter and transition zone. Univariate (Kendall correlation and Student t test) and multivariable (general linear regression and logistic regression) analyses were performed.RESULTS:We enrolled 138 patients (66.7% women, mean age 57.1 years) in this study. Lower PCI was associated with an elevated risk of increased pharyngeal reflux (adjusted odds ratio 0.83 per 100 mm Hg-s-cm change in PCI, 95% confidence interval: 0.69–0.98), with a trend toward increased bolus exposure time and total reflux events, after multivariable adjustment. The relationship between PCI and pharyngeal reflux was strongest among participants without a primary motility disorder on HRM (adjusted odds ratio 0.63, 95% confidence interval: 0.42–0.85, P interaction = 0.04). Among continuously expressed reflux parameters, lower PCI was significantly associated with more distal acid reflux events (β = −0.0094, P = 0.03) and total reflux events (β = −0.0172, P = 0.05), after adjusting for confounders.DISCUSSION:Reduced proximal esophageal contractility as assessed by decreased PCI on HRM independently predicted increased pharyngeal reflux in patients with LPR symptoms, particularly among those without a coexisting motility disorder.

Pepsin in gastroesophageal and extraesophageal reflux: molecular pathophysiology and diagnostic utility.

Gastroesophageal and extraesophageal reflux are prevalent and costly diseases. Recognition of the pathogenicity of nonacid reflux has stimulated interest in alternatives to acid-targeting diagnostics and therapeutics. Pepsin is the most deleterious enzyme in refluxate, eliciting inflammatory and carcinogenic effects irrespective of acid. Its presence in all refluxate and detection in saliva have situated pepsin as the most widely researched biomarker for reflux today. This review summarizes emerging findings regarding pepsin-mediated damage during reflux and developments in pepsin-targeting diagnostics. New evidence supports a role for pepsin in epithelial--mesenchymal transition, an important process in carcinogenesis and fibrosis. The first global transcriptomic analysis of pepsin-exposed laryngeal cells was described, yielding evidence of a putative airway pepsin receptor. Evaluation of pepsin diagnostics highlighted the need for rigorous validation in which pepsin concentrations are corroborated by a secondary quantitative assay, and reflux is confirmed or excluded by multichannel intraluminal impedance pH testing. Standards for sample collection and storage, and normative and pathological values are lacking. Progress continues to be made in our understanding of pepsin-mediated damage with implications for novel therapeutic strategies. Salivary pepsin diagnostics continue to garner interest; however, further work appears necessary to improve their accuracy and reproducibility.

The utility of multichannel intraluminal impedance-pH testing in tailoring the management of paediatric gastro-oesophageal reflux disease.

To determine whether combined multichannel intraluminal impedance and pH (MII-pH) testing led to a change in management of children with gastro-oesophageal reflux disease (GORD). Retrospective chart review was done in all patients who underwent MII-pH testing for GORD symptoms at Sydney Children's Hospital between 2008 and 2016. Changes to anti-reflux medications and referral for anti-reflux surgery were evaluated. There were 365 patients, 260 (71.2%) of whom were on acid-suppressing therapy. The median age was 4.1±4.8years, 205 patients (56%) were males, 83 (22.7%) were infants (<1year of age) and 145 (39.7%%) had comorbid conditions. We found 72.1% had abnormal MII-pH results, of which 17.5% had abnormal acid reflux, 8.2% had abnormal number of retrograde bolus movements and 46.3% had hypersensitive oesophagus (positive symptom association only). Infants were significantly more likely to have abnormal MII-pH results compared to older children (P=.04). Results of MII-pH testing led to medication changes in 44.7% and referral for anti-reflux surgery in 6.8% of patients. Combined multichannel intraluminal impedance and pH testing is clinically useful in the management of children with symptoms of GORD and over half the patients had changes to their medical treatment or referral for anti-reflux surgery based on the results of MII-pH testing. It resulted in a treatment change in an additional 32% of patients over traditional pH-metry.

The evaluation of recumbent reflux by multichannel intraluminal impedance pH testing for patients with gastroesophageal reflux disease and sleep disturbance.

The relationship between gastroesophageal reflux disease (GERD) and sleep disturbance has recently been pointed out and is garnering substantial attention. Although there are reports that point out the effectiveness of medical treatment for sleep disturbance associated with GERD, examinations of the pathological condition, including reflux during sleep, are inadequate. In the present study, we evaluated the recumbent reflux in patients with GERD and sleep disturbance using multichannel intraluminal impedance pH (MII-pH), and attempted to suppress recumbent reflux by surgical treatment to examine the pathophysiology of patients with GERD and sleep disturbance. Of the 47 patients with GERD-related diseases in whom laparoscopic fundoplication was performed at The Jikei University Hospital from January 2016 to June 2017, 31 patients (average age: 55.9 ± 13.8years, male in 25), excluding 9 with surgical indications only for esophageal hiatal hernia and 7 without postoperative evaluation, were the subjects of this study. All surgical procedures were performed by the Toupet method. We used the Pittsburgh Sleep Quality Index (PSQI) to evaluate sleep disturbance, setting 5.5 as the cut-off value, based on the report by Doi et al., with any conditions beyond this value deemed sleep disturbance. The evaluation of gastroesophageal reflux was carried based on the MII-pH using the Sleuth, manufactured by Sandhill Corporation, with an automatic analysis carried out by computer. Furthermore, recumbent abnormal reflux was defined as recumbent all reflux (times) > 7. All evaluations were performed preoperatively and at 3months after the operation. The data were expressed in medians and interquartile ranges, with p < 0.05 defined as statistically significant by the Mann-Whitney, Wilcoxon, or Chi-squared test. Although sleep disturbance was found in 19 cases (61%), 8 (42%) of which were actually confirmed as nighttime abnormal reflux, of whom 5 cases (63%) showed significant improvement in their sleep disturbance following the operation, with a PSQI score of lower than 5.5. Among these 5 cases, postoperative recumbent abnormal reflux was also significantly reduced as compared with the preoperative condition (17 vs. 2 times/day, p = 0.042). Furthermore, sleep disturbance improved and recumbent abnormal reflux also decreased in two cases, with sleep disturbance improved by controlling the nighttime reflux via surgery in a total of 7 cases (87.5%). Although the PSQI score was as high as 14 points before and after the operation in one case, the rate of recumbent abnormal reflux was remarkably reduced, with sleep disturbance and recumbent reflux considered irrelevant. Furthermore, regarding the frequency of recumbent acid/non-acid reflux, while non-acid reflux was significantly more frequent in the patients with recumbent reflux complications (9 vs. 1 time/day, p < 0.001), there was no marked difference in the frequency of acid reflux. Among cases with GERD and sleep disturbance, approximately one-third of them showed findings suggestive of the involvement of recumbent reflux in sleep disturbance, with reflux characterized by non-acid reflux.

364 Shorter Esophageal Length Is Associated With Increased Proximal Reflux and Symptom Severity in Patients Presenting With Laryngopharyngeal Reflux (LPR) Symptoms

INTRODUCTION: Laryngopharyngeal reflux (LPR) is a heterogeneous condition with various underlying pathologies. The effect of esophageal anatomy on LPR is unclear. Shorter distance between lower esophageal sphincter (LES) and upper esophageal sphincter (UES) may allow refluxate to more easily reach the pharynx. We aimed to examine the effect of esophageal length on reflux parameters and symptoms. METHODS: 115 consecutive patients (64% female, mean age 53.9 yrs) with suspected LPR referred for high-resolution manometry (HRM) and combined hypopharyngeal-esophageal multichannel intraluminal impedance-pH testing (HEMII-pH) at a tertiary center in 3/2018-5/2019 were enrolled. Validated symptom surveys were prospectively collected at time of testing, including Reflux Symptom Index (RSI) and 12-item short-form health survey (SF-12) for health-related quality of life (HRQOL). Esophageal length was measured from the distal margin of UES to the proximal margin of LES on HRM. Univariate analyses were performed with Pearson correlation or Student’s t-test. Generalized linear regression was used for multivariate analysis. RESULTS: Mean esophageal length on HRM was 20.4 cm (SD = 2.2). Esophageal length was significantly shorter among patients with a hiatal hernia ≥2 cm (19.2 cm vs 20.6 cm, P = 0.01), but did not correlate with any primary motility disorder per Chicago classification v3.0. Shorter esophageal length was significantly associated with higher acid exposure time and proximal reflux events on impedance, with a trend toward more total reflux events (Table 1). Esophageal length was also shorter among patients with pharyngeal reflux events on HEMII-pH compared to those without (20.0 cm vs 20.9 cm, P = 0.04). Even after controlling for hiatal hernia size, esophageal length remained independently predictive of reflux severity and pharyngeal reflux events. There was a correlation between shorter esophageal length and more severe symptoms on the heartburn/chest pain/indigestion subscore of RSI, but not total RSI or throat symptom subscores (Table 2). Shorter esophageal length was associated with lower physical health scores on SF-12 for HRQOL (Figure 1). CONCLUSION: Shorter esophageal length is independently associated with increased reflux severity, proximal reflux, and pharyngeal reflux, even after controlling for hiatal hernia size. It also correlates with more severe typical reflux symptoms and physical HRQOL. Decreased esophageal length may play a role in the pathophysiology of reflux in patients with LPR symptoms.

Correlation of salivary and nasal lavage pepsin with MII-pH testing.

Laryngopharyngeal reflux (LPR) is a common upper airway disease. Salivary pepsin is a proposed marker for LPR; however, the optimal time for collection of specimens for pepsin detection and pepsin's presence in the oral and nasal secretions relative to concurrent multichannel intraluminal impedance-pH (MII-pH) monitoring are unknown. Prospective case-control study with an experimental design. Patients undergoing MII-pH testing for evaluation of LPR and asymptomatic control subjects were selected. Nasal lavage and saliva samples were collected in the clinic prior to MII-pH probe placement. Additional saliva samples were obtained an hour after each meal and upon waking the following morning. Nasal lavage and salivary pepsin were measured by ELISA. Twenty-six patients undergoing MII-pH testing and 13 reflux-free control patients were enrolled. Salivary pepsin was detected in 11 of 26 patients with suspected LPR and 0 of 13 controls. Pepsin was most frequently detected in the specimen provided upon waking at an average concentration of 186.9 ng/mL. A significant correlation was observed between salivary pepsin in waking samples to MII-pH measurements, including reflux bolus duration, and proximal and distal recumbent reflux episodes (P < 0.05). A significant correlation was also observed between salivary pepsin upon waking or sinus lavage and reflux symptom index (P < 0.05). Pepsin in salivary and nasal lavage samples demonstrated an association with MII-pH-documented LPR. Pepsin detection was most frequent in morning samples, supporting use of morning salivary pepsin levels as a potential noninvasive technique for LPR diagnosis. 2 Laryngoscope, 130:961-966, 2020.

Gastric Emptying Time, Esophageal pH-Impedance Parameters, Quality of Life, and Gastrointestinal Comorbidity in Obese Children and Adolescents

To provide further evidence regarding the relationship between obesity and gastroesophageal reflux disease (GERD) in children, through the use of 13C-octanoic acid breath test for gastric emptying time (GET) assessment and esophageal multichannel intraluminal impedance pH-testing (MII-pH). Obese children aged 4-17 years completed a questionnaire investigating reflux symptoms, the presence of functional gastrointestinal disorders, and quality of life. A subgroup of obese patients with and without GERD symptoms were asked to undergo 13C-octanoic acid breath test. Symptomatic patients were also required to undergo MII-pH. Age- and sex- matched asymptomatic nonobese children were enrolled as a comparison group. Of 113 enrolled patients, 44 (38.9%) reported reflux symptoms; 22 of the 44 underwent MII-pH. Their mean reflux index was 14.6%, and their mean number of daily reflux episodes was 51.8. The mean T½ GET of symptomatic was 107.6 minutes vs 116.5 minutes in asymptomatic obese children. Healthy nonobese children had a mean T½ GET of 100.1 minutes. The mean GET of symptomatic obese patients having >70 daily reflux events was 121.8 vs 87.6 minutes of patients with <70 daily reflux events (P <.05). Both symptomatic and asymptomatic obese patients had a worse quality of life than nonobese (P = 0.003 and P = 0.0002, respectively); a narrow waist circumference was directly related to GET (P = 0.01). A high percentage of obese children and adolescents experience GERD symptoms. GET was directly related to the narrow waist circumference of obese children with GERD and was significantly delayed in obese children with increased reflux events. Both symptomatic and asymptomatic obese patients had a worse quality of life compared with nonobese healthy patients.

Combined Multichannel Intraluminal Impedance and pH Measurement in Detecting Gastroesophageal Reflux Disease in Children.

The aim of the study was to evaluate and compare multichannel intraluminal impedance-pH (MII-pH) monitoring with standard investigations including pH testing for detecting gastroesophageal reflux disease (GERD) in children. A retrospective review of all MII-pH studies performed between July 2007 and March 2013 at Sydney Children's Hospital. Results from MII-pH testing, esophagogastroduodenoscopy (EGD), barium meal and pepsin assay, symptoms, underlying comorbidities, age, and medication usage were evaluated. An additional 47.18% of children had GERD detected by MII-pH testing, which would have been missed by pH testing alone. Based on symptomatology, 50.49% of children with respiratory symptoms as a result of GERD and 47.54% of those with gastrointestinal symptoms would have been missed by pH testing alone. GERD was detected in an additional 39.47% of children with neurological impairment, 44.44% for those with cystic fibrosis, and 52.17% for those with esophageal atresia-tracheoesophageal fistula by MII-pH. In patients with persistent symptoms on anti-reflux medication, GERD would have been missed by pH testing alone in 50.40%. GERD was detected in an additional 62.79% of infants and 42.76% of older children by MII-pH compared with pH testing alone. With reference to MII-pH, the sensitivity of other standard investigations, pH testing (32.35%), barium meal (25.00%), EGD (45.26%), and pepsin assay (48.89%) was significantly lower in the detection of GERD in children. Of all abnormal MII-pH results, 51.1% were abnormal because of symptom association alone. Combined MII-pH testing is superior to standard investigations such as 24-hour pH testing, barium meal, EGD, and pepsin assay in detecting GERD in children, particular because of its ability to associate symptoms with acid and non-acid reflux events.

Esophageal acid exposure analysis: with or without impedance?

Background: The pH data of multichannel intraluminal impedance-pH testing (MII-pH) may be analyzed by using all pH drops (simulating traditional pH-monitoring) or only analyzing pH drops associated with impedance changes. It is unknown whether the acid exposure measurements would differ between these methods in a group of symptomatic patients. Methods: We evaluated MII-pH studies of patients from 2008 to 2013. Acid analysis was performed in two methods: 1. Creating non-mealtime pH measurements related to retrograde bolus movements (“pH-MII method”) 2. Creating non-mealtime pH measurements anytime the pH fell below 4 (“all-pH method”). Statistical analysis was performed using t-test, Fischer’s test, and logistic regression. Results: 121 patients were eligible. The mean percent total acid exposure time (4.05) was significantly higher in the all-pH method (vs. 1.63 p=0.001). The proportion of patients with abnormal acid exposure time (24.7%) and DeMeester score (24.8%) was higher in the all-pH method (vs. 8.3%, p=0.001; vs. 9.1%, p=0.002). Compared to those without a hiatal hernia (HH), more patients with a HH >2cm had significant differences between analysis methods in upright (19.4% vs. 5.56%, p=0.03), recumbent (29% vs. 6.67%; p=0.002), total time (45.2% vs. 6.67%, p=0.001), and DeMeester score (35.5% vs. 8.89%; p=0.001). Adjusting for age, sex, and PPI usage, HH remained a significant predictor of whether results would differ (OR 12; CI 3.34-42.8 total exposure, OR 8.75; CI 2.36-32.5 DeMeester). Conclusion: Analysis of esophageal acid exposure using all pH data detected more acid reflux than when incorporating impedance measures, particularly in those with a HH. This finding may relate to small volume reflux. Therefore analysis of all-pH reflux rather than just MII-pH should be considered in those patients with a HH.

Impaired Esophageal Mucosal Integrity May Play a Causative Role in Patients With Nongastroesophageal Reflux Disease-Related Noncardiac Chest Pain.

Baseline impedance (BI) measurement can be used to evaluate the status of the esophageal mucosa integrity. We hypothesized that impaired esophageal mucosal integrity may play a causative role in patients with nongastroesophageal reflux disease (non-GERD)–related noncardiac chest pain (NCCP). This retrospective study analyzed 24-hour multichannel intraluminal impedance-pH testing data from 77 patients with NCCP and 5 healthy volunteers. BI was calculated at 3 cm (distal esophagus) and 17 cm (proximal esophagus) above the lower esophageal sphincter. GERD was defined by the presence of pathologic acid exposure or reflux esophagitis. Among the 77 patients with NCCP, 16 (20.8%) were classified into the GERD-related NCCP group and 61 (79.2%) into the non-GERD-related NCCP group. BI (median, interquartile range) of the non-GERD-related NCCP group was lower than the control group at the proximal esophagus (2507 Ω, 2156–3217 vs 3855 Ω, 3238–4182, P = 0.001) but was similar at the distal esophagus. The GERD-related NCCP group showed lower BI than the control group at both the distal and proximal esophagus (2024 Ω, 1619–2308 vs 3203 Ω, 2366–3774, P = 0.007 and 2272 Ω, 1896–2908 vs 3855 Ω, 3238–4182, P = 0.003, respectively). At the distal esophagus, BI was lower in the GERD-related NCCP group than the non-GERD-related NCCP group (P = 0.002), whereas it did not differ between the 2 groups at the proximal esophagus. In conclusion, the mucosal integrity is impaired at the proximal esophagus in patients with non-GERD-related NCCP, which might be the pathogenic mechanism of NCCP.

Correlation between hypersensitivity induced by esophageal acid infusion and the baseline impedance level in patients with suspected gastroesophageal reflux.

To evaluate the relevance between the pH parameters and baseline impedance level or esophageal hypomotility in patients with suspected gastroesophageal reflux. The recordings of 51 patients with heartburn, acid regurgitation, globus or noncardiac chest pain were analyzed. Evaluation included a 24-h multichannel intraluminal impedance-pH test while on off-proton pump inhibitor therapy over 1week, high-resolution manometry and Bernstein test. Mean baseline impedance level at the most distal portion of the impedance channel was assessed manually. Esophageal hypomotility was evaluated using transitional zone defect (TZD) and distal break (DB) length measurement. In the study subjects (n=51), 6 had a DeMeester score of more than 14.7 and 14 had a positive symptom index. The Bernstein test was positive in ten patients. The baseline impedance level was inversely correlated with the acid exposure time% (r=-0.660, P<0.001). Also, all reflux and weakly acid reflux time % measured by impedance monitoring showed a weak correlation with TZD+DB length (r=0.327 and 0.324, P=0.019 and 0.020, respectively). Although a positive Bernstein test has no relevance for the acid exposure time or acid-related symptoms as represented by the DeMeester score or symptom index, the baseline impedance level was significantly lower in patients with a positive Bernstein test than in those with a negative one (2,628.4±862.7 vs. 1,752.2±611.1Ω, P=0.004). A lower baseline impedance level is closely related to increased esophageal acid exposure. Hypersensitivity induced by esophageal acid infusion might be attributed to acid-induced mucosal changes of the esophagus.

Tu1976 The 4 Phases of Swallowing: a Functional Model Based on Esophageal Pressure Topography Landmarks

OBJECTIVES: Noncardiac chest pain (NCCP) is defined as recurrent chest pain which does not originate from cardiac cause. Gastroesophageal reflux disease (GERD) is themost common cause of NCCP. However, there are patients presenting NCCP whose symptom is not related with GERD. This study aims to evaluate novel mechanism of non-GERD-related NCCP using high-resolution impedance manometry (HRIM) and 24-hour multichannel intraluminal impedance-pH (MII-pH) testing. PATIENTS AND METHODS: This retrospective study was conducted at Samsung Medical Center between June 2011 and December 2012. A total of 77 NCCP patients and 14 healthy volunteers (control group) were included. The subjects underwent upper endoscopy, esophageal HRIM and 24-hr MII-pH testing. According to the presence of erosive esophagitis and/or pathologic acid exposure, patients were divided into GERD-related group and non-GERD-related group. We measured mean esophageal baseline intraluminal impedances and investigated esophageal motility disorders and/or peristaltic abnormalities. The mean baseline intraluminal impedance was measured at distal and proximal esophagus, 3 cm and 17 cm above the lower esophageal sphincter. The esophageal motility disorders and peristaltic abnormalities were determined by Chicago classification. RESULTS: Among 77 NCCP patients, 16 (11.7%) were included in GERD-related group and 61 (88.3%) were included in non-GERD-related group. The distal mean baseline intraluminal impedance did not differ between NCCP patients and control group. However, the proximal mean baseline intraluminal impedance was lower in NCCP patients than in control group (2463±631 vs. 3739±486 V, P<0.001). In subgroup analysis, the distal mean baseline intraluminal impedance was lower only in GERD-related group than in non-GERD-related NCCP group (1924±802 vs. 2666±804 V, P<0.001) and control group (1924±802 vs. 3739±486 V, P=0.02). There was no difference in distal mean baseline intraluminal impedance between non-GERD-related group and control group. On the contrary, the proximal mean baseline intraluminal impedance was lower both in GERD-related (2391±711 vs. 3739±486V, P<0.001) and non-GERD-related group (2482±614 vs. 3739±486V, P<0.001) than in control group. The proximal mean baseline intraluminal impedance did not differ between GERD-related and non-GERD-related group. There was no difference in esophageal motility disorders, peristaltic abnormalities or impaired bolus transit among these groups. CONCLUSIONS: The proximal esophageal mucosal integrity impairment may play a causative role in patients with non-GERD-related NCCP. The proximal mucosal integrity seems to be impaired by another mechanism rather than esophageal hypomotility and impaired bolus transit.

Tu1975 The Impairment of Proximal Esophageal Mucosal Integrity May Play a Causative Role in Patients With Noncardiac Chest Pain

OBJECTIVES: Noncardiac chest pain (NCCP) is defined as recurrent chest pain which does not originate from cardiac cause. Gastroesophageal reflux disease (GERD) is themost common cause of NCCP. However, there are patients presenting NCCP whose symptom is not related with GERD. This study aims to evaluate novel mechanism of non-GERD-related NCCP using high-resolution impedance manometry (HRIM) and 24-hour multichannel intraluminal impedance-pH (MII-pH) testing. PATIENTS AND METHODS: This retrospective study was conducted at Samsung Medical Center between June 2011 and December 2012. A total of 77 NCCP patients and 14 healthy volunteers (control group) were included. The subjects underwent upper endoscopy, esophageal HRIM and 24-hr MII-pH testing. According to the presence of erosive esophagitis and/or pathologic acid exposure, patients were divided into GERD-related group and non-GERD-related group. We measured mean esophageal baseline intraluminal impedances and investigated esophageal motility disorders and/or peristaltic abnormalities. The mean baseline intraluminal impedance was measured at distal and proximal esophagus, 3 cm and 17 cm above the lower esophageal sphincter. The esophageal motility disorders and peristaltic abnormalities were determined by Chicago classification. RESULTS: Among 77 NCCP patients, 16 (11.7%) were included in GERD-related group and 61 (88.3%) were included in non-GERD-related group. The distal mean baseline intraluminal impedance did not differ between NCCP patients and control group. However, the proximal mean baseline intraluminal impedance was lower in NCCP patients than in control group (2463±631 vs. 3739±486 V, P<0.001). In subgroup analysis, the distal mean baseline intraluminal impedance was lower only in GERD-related group than in non-GERD-related NCCP group (1924±802 vs. 2666±804 V, P<0.001) and control group (1924±802 vs. 3739±486 V, P=0.02). There was no difference in distal mean baseline intraluminal impedance between non-GERD-related group and control group. On the contrary, the proximal mean baseline intraluminal impedance was lower both in GERD-related (2391±711 vs. 3739±486V, P<0.001) and non-GERD-related group (2482±614 vs. 3739±486V, P<0.001) than in control group. The proximal mean baseline intraluminal impedance did not differ between GERD-related and non-GERD-related group. There was no difference in esophageal motility disorders, peristaltic abnormalities or impaired bolus transit among these groups. CONCLUSIONS: The proximal esophageal mucosal integrity impairment may play a causative role in patients with non-GERD-related NCCP. The proximal mucosal integrity seems to be impaired by another mechanism rather than esophageal hypomotility and impaired bolus transit.

Multichannel Intraluminal Impedance–pH Testing Is Clinically Useful in the Management of Patients with Gastroesophageal Reflux Symptoms

Multichannel intraluminal impedance-pH testing (MII-pH) allows for the detection of acid and non-acid reflux, thus, increasing yield over pH testing. Limited data exist on how physicians use test results in practice. The aim of our study was to evaluate the influence of MII-pH testing on patient care. We reviewed records of patients with symptoms of gastroesophageal reflux disease who underwent MII-pH testing. Management decisions evaluated included changes in prescribed medications and surgical consultation for anti-reflux surgery. Statistical analysis was performed using Pearson Chi square test, and multivariable logistic regression. MII-pH testing resulted in a medication change in 41% of patients, surgical consultation in 19.7%, and anti-reflux surgery in 11.1%. In patients who were not on proton pump inhibitor (PPI) therapy, MII-pH results were most useful in the decision to start a PPI. On PPI therapy, results were more often used to decide whether to increase (32.3%) or switch the PPI (23.5%) in patients with continued acid reflux. Results were most useful to stop the PPI in normal studies (11.1%). More patients with non-acid reflux (14.3%) and normal results (19.7%) were started on a neuromodulator compared to other diagnoses. The MII-pH result was most useful in the decision to start baclofen or bethanecol when the patient was found to have non-acid reflux (25%). Patients with an abnormal MII-pH or abnormal MII alone were more likely to be referred to surgery (OR 19.5, p < 0.001; OR 19.77, p < 0.001). MII-pH testing impacted medical or surgical management in over half the patients tested.

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.