Esophageal Mucosal Integrity Research Articles

Comparison between Conventional and Simple Measuring Methods of Mean Nocturnal Baseline Impedance in Pediatric Gastroesophageal Reflux Disease.

(1) Background: Multichannel intraluminal impedance-pH (MII-pH) monitoring is commonly used to diagnose gastroesophageal reflux disease (GERD). The mean nocturnal baseline impedance (MNBI) is an important parameter, reflecting the esophageal mucosal integrity and improvement in GERD. This study aims to evaluate the correlation between conventionally measured MNBI and a recently described simple MNBI measurement method in diagnosing pediatric GERD. (2) Methods: This prospective observational study enrolled 64 children aged one month to 18 years who underwent 24 h MII-pH monitoring. Conventional MNBI was measured during stable 10 min intervals at night, while the simple MNBI method averaged impedance throughout the nocturnal supine period. (3) Results: Strong correlations were found between conventional and simple MNBI values across all impedance channels in both infants (r > 0.85) and older children (r > 0.9). Conventional and simple MNBIs in the most distal channel (Z6) effectively differentiated non-erosive reflux disease (NERD) from other phenotypes, with AUCs of 0.864 and 0.860, respectively. The simple MNBI demonstrated good diagnostic performance with similar sensitivity and specificity to the conventional MNBI. (4) Conclusions: Including MNBI measurements into routine MII-pH monitoring may enhance GERD diagnosis and reduce the need for more invasive procedures.

How to diagnose GERC more effectively: reflections on post-reflux swallow-induced peristaltic wave index and mean nocturnal baseline impedance

IntroductionPost-reflux swallow-induced peristaltic wave index (PSPWI) and mean nocturnal baseline impedance (MNBI) are novel parameters reflect esophageal clearance capacity and mucosal integrity. They hold potential in aiding the recognition of gastroesophageal reflux-induced chronic cough (GERC). Our study aims to investigate their diagnostic value in GERC.MethodsThis study included patients suspected GERC. General information and relevant laboratory examinations were collected, and final diagnosis were determined following guidelines for chronic cough. The parameters of multichannel intraluminal impedance-pH monitoring (MII-pH) in patients were analyzed and compared to explore their diagnostic value in GERC.ResultsA total of 186 patients were enrolled in this study. The diagnostic value of PSPWI for GERC was significant, with the area under the working curve (AUC) of 0.757 and a cutoff value of 39.4%, which was not statistically different from that of acid exposure time (AET) (p > 0.05). The combined diagnostic value of AET > 4.4% and PSPWI < 39.4% was superior to using AET > 4.4% alone (p < 0.05). Additionally, MNBI and distal MNBI also contributed to the diagnosis of GERC, with AUC values of 0.639 and 0.624, respectively. AET > 4.4% or PSPWI < 39.4% is associated with a 44% reduction in missed diagnoses of non-acid GERC compared to AET > 6.0% or symptom association probability (SAP) ≥ 95%, and may be more favorable for identifying GERC.ConclusionThe diagnostic value of PSPWI for GERC is comparable to that of AET. Combining PSPWI < 39.4% or AET > 4.4% can improve the diagnostic efficiency by reducing the risk of missed diagnoses in cases where non-acid reflux is predominant. Distal MNBI and MNBI can serve as secondary reference indices in the diagnosis of GERC.

Esophageal Baseline Impedance is Associated with Laryngopharyngeal Reflux and Treatment Response.

To evaluate the efficacy of distal esophageal mean nocturnal baseline impedance (MNBI), a general marker of esophageal mucosal barrier integrity, in predicting laryngopharyngeal reflux (LPR) and symptomatic response to acid reflux therapy. This retrospective study analyzed 173 patients who presented with symptoms of laryngopharyngeal reflux and underwent 24-h multichannel intraluminal impedance-pH (MII-pH) testing. Mean nocturnal baseline impedance values were calculated and assessed for their association and ability to predict LPR symptoms, MII-pH results, treatment response, and other markers of LPR. Notably, 153 of the 173 patients were tested off acid suppression medication and included in statistical analysis. Based on the MII-pH probe data, 108 (71%) patients had LPR, 8 (5%) had gastroesophageal reflux disease (GERD), and 37 (24%) were without pathologic reflux. Distal esophageal MNBI of LPR patients was significantly lower in LPR patients than patients with negative studies (1332 ± 94.8 vs. 2158 ± 173.5, p = 0.001). Among 118 patients who trialed antireflux therapy, a distal esophageal MNBI cutoff value of <1580 Ω was an independent predictor of treatment response (OR = 4.148 [1.877-9.189]). This value better predicted improvement with antireflux therapy for LPR than other objective MII-pH probe data, which were not independent predictors of treatment response. Distal esophageal MNBI values may have value in the diagnosis of LPR and potentially predict medication responsiveness in LPR patients. 3 Laryngoscope, 134:4071-4077, 2024.

Mucosal impedance as a diagnostic tool for gastroesophageal reflux disease: an update for clinicians.

Mucosal impedance is a marker of esophageal mucosal integrity and a novel technique for assessing esophageal function and pathology. This article highlights its development and clinical application for gastroesophageal reflux disease (GERD), Barrett's esophagus, and eosinophilic esophagitis. A narrative review of key publications describing the development and use of mucosal impedance in clinical practice was conducted. A low mean nocturnal baseline impedance (MNBI) has been shown to be an independent predictor of response to anti-reflux therapy. MNBI predicts medication-responsive heartburn better than distal esophageal acid exposure time. Patients with equivocal evidence of GERD using conventional methods, with a low MNBI, had an improvement in symptoms following the initiation of PPI therapy compared to those with a normal MNBI. A similar trend was seen in a post fundoplication cohort. Strong clinical utility for the use of mucosal impedance in assessing eosinophilic esophagitis has been repeatedly demonstrated; however, there is minimal direction for application in Barrett's esophagus. The authors conclude that mucosal impedance has potential clinical utility for the assessment and diagnosis of GERD, particularly when conventional investigations have yielded equivocal results.

Pathophysiology of gastro-oesophageal reflux disease: implications for diagnosis and management.

Gastro-oesophageal reflux disease (GERD) is a common gastrointestinal disorder in which retrograde flow of gastric content into the oesophagus causes uncomfortable symptoms and/or complications. It has a multifactorial and partially understood pathophysiology. GERD starts in the stomach, where the refluxate material is produced. Following the trajectory of reflux, the failure of the antireflux barrier, primarily the lower oesophageal sphincter and the crural diaphragm, enables the refluxate to reach the oesophageal lumen, triggering oesophageal or extra-oesophageal symptoms. Reflux clearance mechanisms such as primary and secondary peristalsis and the arrival of bicarbonate-rich saliva are critical to prevent mucosal damage. Alterations of the oesophageal mucosal integrity, such as macroscopic oesophagitis or microscopic changes, determine the perception of symptoms. The intensity of the symptoms is affected by peripheral and central neural and psychological mechanisms. In this Review, we describe an updated understanding of the complex and multifactorial pathophysiology of GERD. It is now recognized that different GERD phenotypes have different degrees of reflux, severity of mucosal integrity damage and type, and severity of symptoms. These variations are probably due to the occurrence of a predominant pathophysiological mechanism in each patient. We also describe the main pathophysiological mechanisms of GERD and their implications for personalized diagnosis and management.

Ziverel for PPI-refractory reflux symptoms: efficacy and mechanisms of action in humans

Objectives It is thought that esophageal hypersensitivity in combination with an impaired mucosal barrier function contributes to PPI-resistant reflux symptoms. Ziverel, a bioadhesive agent that coats the esophageal wall, was shown to have a positive effect on reflux symptoms. However, the mechanisms of action are unclear. We aimed to assess the effect of Ziverel on esophageal sensitivity to acid and mucosal barrier function. Methods We performed a double-blind randomized placebo-controlled crossover trial in PPI-refractory patients with reflux symptoms. Patients were assigned (1:1) to 14 days of Ziverel followed by 14 days of placebo or opposite treatment order. The effect was evaluated using acid perfusion tests, an upper endoscopy with electrical tissue impedance spectroscopy (ETIS) and esophageal biopsies. The primary outcome was the esophageal sensitivity based on perfusion sensitivity score. Secondary outcomes included mucosal barrier function and reflux symptoms and correlations between the different outcomes. Results Perfusion sensitivity score was not significantly different during treatment with Ziverel (106 (73–115)) and placebo (102 (67–110)) (p = 0.508) along with total RDQ score (2.6 (1.9–3.3) vs 2.8 (1.6–3.5) p = 0.456). ETIS showed comparable values during treatment with Ziverel (13514 (8846–19734)Ω·m) and placebo (13217 (9127–24942)Ω·m (p = 0.650)). Comparing Ziverel and placebo no difference was seen in transepithelial electrical resistance (TEER) 203 (163–267) Ω.cm2 vs 205 (176–240) Ω.cm2 (p = 0.445) and fluorescein flux 775 (17–6964) nmol/cm2/h vs 187 (4–12209) nmol/cm2/h (p = 0.638). Conclusion Ziverel did not show a benefit on acid sensitivity, reflux symptoms or esophageal mucosal integrity compared to placebo in PPI-refractory patients with reflux symptoms. Trial registration: Netherlands Trial Register number: NL7670

Small intestinal bacterial overgrowth is associated with laryngopharyngeal reflux symptom severity and impaired esophageal mucosal integrity

Objectives: To explore the relationship between small intestinal bacterial overgrowth (SIBO) and laryngopharyngeal reflux (LPR). Methods: Data from patients undergoing high resolution manometry, pH-impedance monitoring, and hydrogen methane breath testing at a single tertiary center were analyzed retrospectively. SIBO was determined by a ≥ 20 ppm rise in breath hydrogen from baseline within 90 minutes after ingestion of lactulose. Patients were grouped by SIBO result and compared for subjective LPR symptoms on the Reflux Symptom Index (RSI) in addition to objective manometric and reflux parameters, including mean nocturnal baseline impedance (MNBI) in the proximal and distal esophagus. Results: Forty-one patients were analyzed, of which 46.3% were positive for SIBO. Patients with SIBO had a significantly greater LPR symptom burden on RSI (26.5 ± 9.3 vs. 16.9 ± 8.9, P = 0.002). Independently, SIBO was associated with throat clearing (P = 0.016), cough (P &lt; 0.001) and globus (P = 0.003). Objectively, there was no difference in manometric or reflux parameters except patients with SIBO had significantly lower MNBI in the proximal esophagus (1970.2 ± 511.6 Ω vs. 2504.2 ± 816.1 Ω, P = 0.026). Conclusion: Patients with SIBO have greater LPR symptom severity and impaired mucosal integrity in the proximal esophagus. Future study should look to determine if treating SIBO improves symptoms of LPR.

Effect of aging and obesity on esophageal mucosal integrity as measured by baseline impedance.

Low mean nocturnal baseline impedance (MNBI) values support gastroesophageal reflux disease (GERD) diagnosis. Recent data denote that age and obesity may affect MNBI. We aimed to evaluate diagnostic MNBI cutoffs as also the effect of aging and body mass index (BMI) on MNBI. In total 311 patients (M/F: 139/172, mean age: 47 ± 13) referred for typical GERD symptoms that have undertaken both high-resolution manometry (HRM) and pH-Impedance studies off PPI were evaluated. MNBI at 3, 5, and 17 cm over lower esophageal sphincter (LES) were evaluated. GERD was diagnosed if acid exposure time (AET) >6%. Mean BMI was 26.6 ± 5.9 kg/cm2 . GERD was diagnosed in 39.2% and 13.5% had inconclusive GERD. MNBI was correlated to patients' age, BMI, AET, and the length of LES-CD separation and at 3 cm also to the total number of reflux and LES hypotension. In the multivariate analysis MNBI at 3 and 5 cm was independently correlated only to age, BMI, and AET. Patients with definite GERD showed lower MNBI at 3 cm compared with inconclusive GERD though both showed lower values when compared with GERD absence. At 3 cm MNBI ability for diagnosing GERD was good (0.815, p < 0.001 95% CI: 0.766-0.863) with an optimal cutoff point of 1281 Ohm. According to our study findings age and BMI affect independently lower esophageal MNBI values in patients evaluated for GERD. MNBI significantly aids toward GERD diagnosis though in a real-life setting MNBI values much lower than the one previously proposed should be used.

Proximal esophageal impedance baseline increases the yield of impedance-pH monitoring for GERD diagnosis and is associated with heartburn response to PPI.

Impairment of esophageal mucosal integrity as assessed by low mean nocturnal baseline impedance (MNBI) measured in the distal esophagus increases the diagnostic yield of impedance-pH in patients with inconclusive GERD diagnosis as defined by Lyon criteria. To assess the diagnostic yield of MNBI measurement in the proximal esophagus, and its relationship with PPI response. Expert review of off-therapy impedance-pH tracings from consecutive patients with heartburn, 80 responders and 80 non-responders to label-dose PPI. Data were compared to those from 36 healthy controls using ROC analysis. Multivariate analysis was performed to measure the strength of association of MNBI with PPI response. A threshold value of 2665 Ω was defined for proximal MNBI by ROC analysis, affording 91.7% sensitivity and 86.5% specificity. Proximal and distal MNBI were significantly lower in non-responder cases as compared to responders. Adding proximal MNBI positivity to pathologic (>6%) acid exposure time (AET) and positive symptom-reflux association, the proportion of patients with abnormal impedance-pH findings increased from 74/160 (46%) to 106/160 (66.3%) (p = 0.0016). Among the 12 patients with pathologic proximal MNBI as the only positive impedance-pH finding, 9 cases (75%) were PPI responders. According to multivariate analysis, AET and pathological distal and proximal MNBI were significantly associated with PPI response, the strongest association observed for proximal MNBI. Impedance baseline assessment in the proximal esophagus may increase the diagnostic yield of impedance-pH monitoring. Heartburn response to PPI is directly related to ultrastructural mucosal damage in the distal and in the proximal esophagus as well.

Esophageal secondary peristalsis following acid infusion and chemical clearance correlate with mucosal integrity and acid sensitivity in GERD patients.

Acid sensitivity can be altered in patients with gastroesophageal reflux disease (GERD). Secondary peristalsis helps clear gastro-esophageal refluxate and residual ingested food bolus. The aim of this study was to investigate the associations among acid sensitivity, esophageal mucosal integrity, chemical clearance, and secondary peristalsis before and after esophageal acid infusion. This was an investigator-initiated, prospective, cross-sectional study. Adult reflux patients underwent high resolution manometry and 24 h impedance-pH monitoring off acid suppression to identify GERD phenotypes, including non-erosive reflux disease (NERD), reflux hypersensitivity (RH), and functional heartburn (FH). Secondary peristalsis was assessed using five rapid 20 mL air injections into the esophagus before and after infusion of hydrochloric acid (0.1 N) into the mid-esophagus. Conventional acid infusion parameters recorded included lag time, intensity rating, and sensitivity score. Chemical clearance was evaluated using the post-reflux swallow-induced peristaltic wave (PSPW), and mucosal integrity was assessed by the mean nocturnal baseline impedance (MNBI) derived from impedance-pH monitoring. A total of 88 patients (age 21-64 years, 62.5% women) completed the study including 12 patients with NERD, 45 with RH, and 31 with FH. There was no significant difference in acid infusion parameters between patients with NERD, RH, and FH. Upon acid infusion, patients who exhibited successful secondary peristalsis had longer lag time, higher MNBI, and shorter bolus contact time than those without secondary peristalsis. Meanwhile, patients with intact PSPW demonstrated significantly higher intensity ratings in response to acid perfusion and higher MNBI than those with impaired PSPW. The lag time correlated positively with MNBI (r = 0.285; p = 0.007). In conclusion, the protective effect of esophageal secondary peristalsis and chemical clearance on esophageal mucosal integrity was demonstrated. Concerning acid sensitivity, longer lag time in patients with intact secondary peristalsis may be attributed to better esophageal mucosal integrity, while stronger intensity ratings may have a greater tendency to induce PSPW and protect esophageal mucosal integrity.

Effect of hiatus hernia on reflux patterns and mucosal integrity in patients with non-erosive reflux disease.

Hiatus hernia (HH) contributes to development of gastroesophageal reflux disease, Barrett's esophagus and esophageal adenocarcinoma. This study was aimed to investigate the influence of HH on reflux patterns and distal esophageal mucosal integrity in non-erosive reflux disease (NERD). We retrospectively analyzed PPI-refractory NERD patients referred to three tertiary referral centers who underwent high-resolution manometry and off-PPI 24-h impedance-pH monitoring (with or without bile spectrophotometry). Patients with HH ≥2cm (HH group, n=42) or no HH (non-HH group, n=40) with similar esophageal acid exposure time (AET 6%-12%) were included. Age, gender, BMI, esophageal motility, AET, and esophageal clearance were similar between the two groups. The HH group had higher numbers of total reflux episodes (p=0.015) with similar proportion of acid/non-acid reflux compared with the non-HH group. Mean nocturnal baseline impedance (MNBI) in the distal esophagus was significantly lower in the HH group than the non-HH group at both 5cm (p=0.002) and 3cm (p=0.015) above the lower esophageal sphincter. Multivariable regression analysis showed that HH, less non-acid reflux and lower post-reflux swallow-induced peristaltic wave index (PSPWI) were independently associated with lower MNBI. Among 31 patients tested with bile spectrophotometry, the HH group had significantly longer bile exposure time than the non-HH group (p=0.011), and bile reflux inversely and significantly correlated with MNBI (rho=-0.75, p &lt; 0.001). Hiatus hernia, less non-acid reflux and lower PSPWI were associated with lower MNBI. HH impairs distal esophageal mucosal integrity, the mechanism of which we speculate to be through excessive bile reflux.

Association between post-reflux swallow-induced peristaltic wave index and esophageal mucosal integrity in patients with GERD symptoms.

Impedance-pH monitoring allows evaluation of esophageal chemical clearance, a response to reflux elicited by the esophago-salivary reflex, by means of the post-reflux swallow-induced peristaltic wave (PSPW) index; mucosal integrity can be evaluated by means of mean nocturnal baseline impedance (MNBI) and is regarded as a GERD marker. Currently, the relationship between PSPW index and MNBI has not yet been fully investigated and represents the aim of the present study. Impedance-pH tracings from consecutive patients were reviewed. ROC analysis and multivariate regression models were generated to evaluate the association between acid exposure time (AET), total refluxes (TRs), PSPW index, and MNBI. Patients were classified by means of AET thresholds and symptom-reflux association indexes into conclusive and inconclusive GERD, reflux hypersensitivity (RH), and functional heartburn (FH). Pathologic MNBI <2292 Ω was defined according to published outcome studies. Two hundred and thirty patients constituted the study cohort. Overall, a significant direct correlation was observed between PSPW index and MNBI (0.759, p<0.001). At ROC analysis, a PSPW index cut-off value of 53% was the best discriminator between normal from pathologic MNBI values (sensitivity 88%, specificity 86.4%). Considering AET cut-off of 4% or 6%, a sensitivity of 80.7% and 46% and a specificity of 62.5% and 93.2% were found, respectively. According to multivariate analysis, AET >4% and PSPW index value <53% or <61% were significantly associated with pathologic MNBI values. Esophageal chemical clearance is a major defense mechanism against reflux and its impairment represents a major determinant of reflux-associated mucosal damage.

Mean nocturnal baseline impedance, a novel metric of multichannel intraluminal impedance-pH monitoring in diagnosing gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is a common disease with increasing prevalence worldwide. However, the diagnosis of GERD is challenging because there are no definite gold standard criteria. Recently, a novel impedance parameter, namely mean nocturnal baseline impedance (MNBI), has been proposed, which reflects the burden of longitudinal reflux and the integrity of esophageal mucosa. MNBI has shown an immense promise for increasing the diagnostic rate of multichannel intraluminal impedance-pH (MII-pH) monitoring and predicting the response to proton pump inhibitor (PPI) or anti-reflux intervention in patients with reflux symptoms. The present paper reviews the association between baseline impedance and esophageal mucosal integrity, the acquisition of MNBI in 24-h MII-pH monitoring, the clinical utilization of MNBI in improving the diagnosis rate of GERD in patients with typical reflux symptoms, predicting the response to PPI or anti-reflux treatment in these patients, the utilization of MNBI in diagnosing patients with atypical symptoms or extra-esophageal symptoms, and the correlation between reflux burden and MNBI. MNBI should be routinely assessed using MII-pH monitoring.

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.

720 CONVENTIONAL AND SIMPLE METHODS OF MEASURING MEAN NOCTURNAL BASELINE IMPEDANCE SHOW EXCELLENT AGREEMENT

Abstract Mean nocturnal baseline impedance (MNBI) is a measurement that shows promise in investigating reflux disease by reflecting esophageal mucosal integrity. The conventional method of measuring MNBI is time-consuming and operator-dependent. A new, simple method of measuring MNBI has been suggested. This study aimed to report MNBI measurements by both conventional and simple methods in a cohort of laryngopharyngeal reflux (LPR) and gastro-esophageal reflux disease (GERD) patients to validate the simple measurement method. Methods 187 patients were divided into LPR (n = 105) or GERD (n = 82) groups by predominant symptom profile, and underwent off-therapy impedance-pH monitoring. MNBI was blindly measured by both conventional and simple methods, and values were correlated. Bland–Altman plots were constructed to assess mean differences and to identify bias between the two measurement methods. Results For the two measurement methods, mean difference in the distal esophagus was −89 (±328) ohms, in the proximal esophagus was −6 (±653) ohms, and in the pharynx was 128 (±577) ohms. There was strong correlation between conventional and simple MNBI values, with r = 0.940 in the distal esophagus, r = 0.463 in the proximal esophagus, and r = 0.712 in the pharynx (all p &amp;lt; 0.001). Conclusion There was excellent agreement between conventional and simple methods of measuring MNBI, with no evidence of proportional bias. Conventional and simple MNBI values correlated excellently in the distal esophagus, and moderately well in the proximal esophagus and pharynx. This study supports the use of the simple method of measuring MNBI to enhance diagnosis of reflux disease.

Obesity and its effects on the esophageal mucosal barrier.

Obesity is associated with gastroesophageal reflux disease (GERD) and its complications including reflux esophagitis, Barrett's esophagus, and esophageal adenocarcinoma. Traditionally, these associations have been attributed to the mechanical effect of abdominal fat in increasing intra-abdominal pressure, thereby promoting gastroesophageal reflux and causing disruption of antireflux mechanisms at the esophagogastric junction. However, recent studies suggest that visceral adipose tissue (VAT) produces numerous cytokines that can cause esophageal inflammation and impair esophageal mucosal barrier integrity through reflux-independent mechanisms that render the esophageal mucosa especially susceptible to GERD-induced injury. In this report, we review mechanisms of esophageal mucosal defense, the genesis and remodeling of visceral adipose tissue during obesity, and the potential role of substances produced by VAT, especially the VAT that encircles the esophagogastric junction, in the impairment of esophageal mucosal barrier integrity that leads to the development of GERD complications.

Oesophageal hypervigilance and visceral anxiety relate to reflux symptom severity and psychological distress but not to acid reflux parameters.

The pathogenesis of gastro-oesophageal reflux disease (GERD) is complex and multifactorial. The oesophageal hypervigilance and anxiety scale (EHAS) is a novel cognitive-affective evaluation of visceral sensitivity. To investigate the interrelationship between EHAS and reflux symptom severity, psychological stress, acid reflux burden, phenotypes, and oesophageal mucosal integrity in patients with GERD. Patients with chronic reflux symptoms and negative endoscopy underwent 24-hour impedance-pH monitoring for phenotyping, acid reflux burden, and mucosal integrity with mean nocturnal baseline impedance (MNBI) calculation. Validated scores for patient-reported outcomes, including EHAS, GERD questionnaire (GERDQ), State-Trait Anxiety Inventory score, and Taiwanese Depression Questionnaire score, were recorded. We enrolled 105 patients, aged 21-64years (mean, 48.8), of whom 58.1% were female; 27 had non-erosive reflux disease, 43 had reflux hypersensitivity and 35 had functional heartburn. There were no significant differences in sex, EHAS, GERDQ, questionnaires of depression or anxiety among GERD phenotypes. EHAS was significantly correlated with GERDQ, questionnaires of depression and anxiety (P<0.05). However, there were no significant correlations between GERDQ and questionnaires of depression or anxiety. Regarding patient-reported outcomes, GERDQ positively correlated with acid exposure time and negatively correlated with MNBI (P<0.05). EHAS associates with reflux symptom severity and psychological stress but not with acid reflux burden or mucosal integrity. Thus, EHAS assessment shows promise in assessment of subjective patient outcome and satisfaction with treatment, a hitherto unmet clinical need.

Conventional and simple methods of measuring esophageal nocturnal baseline impedance show excellent agreement.

Mean nocturnal baseline impedance (MNBI) shows promise in investigating reflux disease by reflecting esophageal mucosal integrity. This study aimed to measure MNBI by both conventional and simple methods in patients with laryngopharyngeal reflux (LPR) and gastroesophageal reflux disease (GERD) in order to evaluate the efficacy of the simple measurement method. Altogether 187 patients were divided into LPR (n=105) or GERD (n=82) groups according to their predominant symptom profile, and underwent off-therapy impedance-pH monitoring. MNBI was measured by both the conventional and simple methods. The Bland-Altman plots were constructed to assess mean differences and to identify bias in the two measurement methods. For the two measurement methods, mean difference was (-89 ± 328) Ω in the distal esophagus, (-6 ± 653) Ω in the proximal esophagus, and (128 ± 577) Ω in the pharynx, respectively. There was a strong correlation between conventional and simple MNBI values, with the coefficient of 0.940 in the distal esophagus, 0.463 in the proximal esophagus, and 0.712 in the pharynx (all P < 0.001). There was an excellent agreement between the conventional and simple methods of MNBI measurement, with no evidence of proportional bias. Conventional and simple MNBI values correlated excellently in the distal esophagus and moderately well in the proximal esophagus and pharynx. This study supports the use of the simple method of measuring MNBI to enhance diagnoses of reflux disease.

Multichannel impedance monitoring for distinguishing nonerosive reflux esophagitis with minor changes on endoscopy in children.

Objectives:There are reports describing the relationship between baseline impedance level and esophageal mucosal integrity at endoscopy, such as erosive and nonerosive reflux esophagitis. However, many children with symptoms of gastroesophageal reflux disease have normal findings or minor changes on esophagogastroduodenoscopy. We aimed to examine whether modest changes at esophagogastroduodenoscopy can be evaluated and correlated with esophageal multichannel intraluminal impedance monitoring.Methods:Patients (ages 0–17 years) with upper gastrointestinal symptoms who underwent combined esophagogastroduodenoscopy and multichannel intraluminal impedance monitoring at the Women’s and Children’s Hospital, Adelaide, Australia, between 2014 and 2016 were retrospectively studied and the following data were collected and used for analysis: demographics, multichannel intraluminal impedance data, included baseline impedance. Endoscopic findings were classified by modified Los Angeles grading, Los Angeles N as normal, Los Angeles M as with minimal change such as the erythema, pale mucosa, or friability of the mucosa following biopsy. Patients on proton pump inhibitor were excluded.Results:Seventy patients (43 boys; 61%) were enrolled with a mean age of 7.9 years (range 10 months to 17 years). Fifty-one patients (72.9%) were allocated to Los Angeles N, while Los Angeles M was evident in 19 patients (27.1%). Statistically significant differences were observed in the following parameters: frequency of acid and nonacid reflux and baseline impedance in channels 5 and 6. The median values of the data were 18.3 episodes, 16.0 episodes, 2461.0 Ω, 2446.0 Ω in Los Angeles N, 36.0 episodes, 31.0 episodes, 2033.0 Ω, 2009.0 Ω in Los Angeles M, respectively.Conclusion:Lower baseline impedance is helpful in predicting minimal endoscopic changes in the lower esophagus. A higher frequency of acid and nonacid reflux episodes was also predictive of minimal endoscopic change in the lower esophagus.

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

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.