Esophageal Sensitivity Research Articles

A212 SYMPTOMS IN PATIENTS WITH NORMAL ESOPHAGEAL MOTILITY MAY DIFFER BASED ON AGE AND SEX

Abstract Background High resolution esophageal manometry (HREM) is used to diagnose esophageal motility disorders. While esophageal symptoms including dysphagia are common and seen in up to 20% of adults, a minority of symptomatic patients have esophageal dysmotility, when defined by the Chicago Classification v4 (CCv4). The generation of esophageal symptoms in a patient with normal esophageal motor function is complex, but may relate to visceral hypersensitivity, inappropriate pain perception or unidentified contraction abnormalities. The Esophageal Symptom Questionnaire (ESQ-30) is a validated tool in the assessment of esophageal symptoms and measures the frequency and severity of dysphagia, reflux and globus through three separate sub-scales (ESQ-D, ESQ-R, ESQ-G respectively). Aims To determine age and sex in esophageal symptoms (as measured by ESQ-30 sub-scales) in a population of symptomatic patients with normal esophageal motility. Methods Retrospective analysis of consecutive reports from HRM studies performed between October 2021 – March 2023 who provided consent for inclusion in the motility databank and completed ESQ-30 questionnaires. All values expressed as median (IQR: 25-75-centile). Spearman’s bivariate correlations were performed between ESQ-D, ESQ-R, ESQ-G and manometric variables (IRP, DCI, % failed, and % weak) as well as demographic variables (age). Group means were compared with the non-parametric Mann-Whitney U test. Results Within the study period, 681 patients underwent HREM and had complete ESQ-30 questionnaires. Of these patients, 151 female and 73 male participants (mean age 51.8 +/- 15.2 years) had normal esophageal motility by CCv4. ESQ-D and ESQ-R scores were significantly higher in women in comparison to men. ESQ-D was 10 in women and 5 in men (p=.021), and ESQ-R was 28 in women and 19 in men (p=.029). There was a weak negative correlation between age and reflux symptoms (R2 -.139, p = 0.038). There was no significant difference in manometric parameters between males and females (p ampersand:003E .05 for all comparisons). Dysphagia and globus weakly negatively correlated with median IRP (R2 -.156, p = .019 and R2 -.139, p = .038 for dysphagia and globus respectively). Conclusions In a population of symptomatic patients with normal esophageal motility, symptom profile differed based on age and sex. Women had higher dysphagia and reflux symptoms compared to men, while older patients had lower reflux symptoms. These findings suggest that esophageal sensitivity may vary with age and sex in patients with normal esophageal motility. The finding of higher dysphagia and globus symptoms in patients with lower median IRP (integrated relaxation pressure) is an unexpected finding and may reflect reflux effect. Further studies to assess for the impact of GERD (using 24h pH-metry/MII) on patients with normal esophageal motor function are warranted. Funding Agencies None

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

The Effect of STW5 (Iberogast) on Reflux Symptoms in Patients With Concurrent Dyspeptic Symptoms: A Double-blind Randomized Placebo-controlled Crossover Trial.

It has been suggested that STW5 (Iberogast) reduces heartburn symptoms in patients with functional dyspepsia, but underlying mechanisms of action are unclear. The aim of this study is to investigate whether STW5 affects esophageal sensitivity or esophageal motility, thereby reducing occurrence and perception of reflux events. We performed a double-blind, randomized, placebo-controlled, crossover trial in patients with functional dyspepsia (Rome IV) and reflux symptoms. After 4 weeks of treatment with either placebo or STW5, patients were studied with an esophageal acid perfusion test and ambulatory 24-hour pH-impedance monitoring. A total of 18 patients (7 men, median age 54, range [19-76]), were included in the study. Although we found no statistical difference in our primary outcome the total Reflux Disease Questionnaire score 2.33 (0.25-4.33) vs 2.67 (1.17-4.00), P = 0.347, "gastroesophageal reflux disease" and "regurgitation" subscale scores were lower after STW5 treatment compared to placebo (P = 0.049 and P = 0.007). There was no statistical difference in number of reflux events, acid exposure time and acid sensitivity scores between STW5 and placebo. In a subgroup analysis of patients with pH-metry confirmed gastroesophageal reflux disease, treatment with STW5 significantly reduced the total number of acidic reflux events (P = 0.028). Moreover, in patients with reflux esophagitis, the median lag time to acid perception increased after STW5 treatment (P = 0.042). We found some indications pointing towards a beneficial effect of STW5 on reflux symptoms in dyspeptic patients, with reduction of esophageal hypersensitivity as a potential underlying mechanism. Our findings will have to be confirmed in larger studies.

Identification of novel immune cell signature in gastroesophageal reflux disease: altered mucosal mast cells and dendritic cell profile.

Heartburn pathogenesis in GERD remains incompletely understood. We aimed to identify differences in the immune cell signature and sensory mucosal markers between reflux phenotypes and healthy asymptomatic subjects. Thirty-seven patients with heartburn symptoms were phenotyped endoscopically and with objective reflux studies into erosive reflux disease (ERD) (N=10), nonerosive reflux disease (NERD) (N=9), functional heartburn (FH) (N=9), and Barrett's esophagus (BO) (N=9). Bulk mRNA-sequencing(RNA-seq) was conducted on RNA extracted from endoscopic biopsies, and immune cell deconvolution analysis was performed using CIBERSORT. RNA-seq findings were validated by immunofluorescent staining for CD1a, nerve growth factor (NGF), and mast cell tryptase in corresponding patient biopsies. Transcriptomic analysis detected higher mast cell abundance in BO, ERD, and NERD compared to healthy controls (p<0.05), with decreased dendritic cell infiltration in BO, ERD, and NERD patients compared to healthy controls and FH patients. CD1a-positive dendritic cell infiltration was significantly higher in the healthy esophageal mucosa at protein level compared to BO (p=0.0005), ERD (p=0.0004), and FH patients (p=0.0096). Moreover, NGF co-expression on mast cells in GERD patients was significantly higher than in healthy controls (p=0.0094). The mucosa in patients with GERD had a significant increase in NGF expression on mast cells, suggesting an upregulation of signalling for neuronal sprouting in GERD. Moreover, decreased dendritic cell abundance in GERD esophageal mucosa may play a role in reduced oral tolerance and development of subsequent immune responses which may participate in esophageal sensitivity.

Sensory Phenotype of the Oesophageal Mucosa in Gastro-Oesophageal Reflux Disease.

Gastroesophageal reflux disease (GORD) affects up to 20% of Western populations, yet sensory mechanisms underlying heartburn pathogenesis remain incompletely understood. While central mechanisms of heartburn perception have been established in earlier studies, recent studies have highlighted an important role of neurochemical, inflammatory, and cellular changes occurring in the oesophageal mucosa itself. The localization and neurochemical characterisation of sensory afferent nerve endings differ among GORD phenotypes, and could explain symptom heterogeneity among patients who are exposed to similar levels of reflux. Acid-induced stimulation of nociceptors on pain-sensing nerve endings can regulate afferent signal transmission. This review considers the role of peripheral mechanisms of sensitization in the amplification of oesophageal sensitivity in patients with GORD.

The relationship between esophageal acidity and symptom frequency in symptomatic nonerosive gastroesophageal reflux disease.

The present paper examines the extent to which novel measures of esophageal acid exposure can elucidate possible relationships between symptom perception and esophageal acidity in subjects with nonerosive gastroesophageal reflux disease. Recordings of esophageal pH and symptom occurrence from 20 subjects with nonerosive gastroesophageal reflux disease were analyzed. Interval esophageal acid exposure was calculated in two different ways for the interval that preceded each symptom in each subject. Interval esophageal acidity was calculated as the time‐weighted acid concentration for the interval. Interval esophageal acid exposure time was calculated as the percentage of the total recording time that esophageal pH was less than pH 4 for the interval. There was a negative relationship between the probability of a symptom and interval esophageal acid exposure indicating the paradoxical finding that the lower the value of esophageal acid exposure, the higher the probability of a symptom. The time courses of symptoms and cumulative esophageal acidity resolved this paradox by indicating that esophageal acid exposure oscillates between longer periods of low esophageal acid exposure with a high number of symptoms reflecting high esophageal acid sensitivity, and shorter periods of high esophageal acid exposure with fewer symptoms reflecting low esophageal acid sensitivity. Thus, the present analyses show how novel measures of acidity can identify and also resolve a previously unrecognized paradoxical relationship between esophageal acid exposure and symptom frequency in subjects with nonerosive gastroesophageal reflux disease.

Impact of esophageal mucosal permeability markers on provocation-induced esophageal reflexes in high-risk infants.

Esophageal distal baseline impedance (DBI) is an indicator of mucosal integrity; lower values suggest increased permeability. Aims were to characterize the (1) effect of DBI category (<900 Ω, 900–2000 Ω, and >2000 Ω) on sensory‐motor characteristics of mid‐esophageal provocation‐induced motility reflexes, and (2) clinical outcomes among high‐risk human infants evaluated for gastroesophageal reflux disease. Symptomatic infants (N = 49, 41 ± 3 weeks postmenstrual age) underwent pH‐impedance testing to characterize acid reflux index (ARI) and DBI, and pharyngo‐esophageal manometry to examine upper esophageal sphincter (UES), peristaltic, and lower esophageal sphincter (LES) functions. Sensory‐motor response characteristics included response threshold (ml), occurrence (%), latency (s), duration (s), and magnitude (mmHg) upon mid‐esophageal stimulations (0.1–2.0 ml of air, water, and apple juice). Motility and clinical outcomes were compared among DBI groups. In infants with DBI <900 Ω and 900–2000 Ω (vs. >2000 Ω): (a) Long‐term feeding milestones did not differ (p > 0.05); (b) complete peristaltic propagation decreased in 900–2000 Ω (p < 0.05), polymorphic waveforms increased in <900 Ω and 900–2000 Ω (p < 0.05); (c) media effects were noted with liquids (vs. air) wherein UES and esophageal contractility were prolonged in <900 Ω and 900–2000 Ω (p < 0.05), and esophageal sensitivity heightened for <900 Ω with water and for 900–2000 Ω with air (both p < 0.05). ARI was not correlated with DBI in infants with chronic lung disease (r = 0.05, p = 0.82). We conclude that pharyngo‐esophageal motility sensory‐motor characteristics in infants are modified by DBI category. These preliminary findings pave‐the‐way for further physiological testing in convalescing high‐risk infants to ascertain potential mechanisms of airway‐digestive reflex interactions and symptom generation, which may lead to targeted therapies.

Systematic review with meta-analysis: artificial intelligence in the diagnosis of oesophageal diseases.

SummaryBackgroundArtificial intelligence (AI) has recently been applied to endoscopy and questionnaires for the evaluation of oesophageal diseases (ODs).AimWe performed a systematic review with meta‐analysis to evaluate the performance of AI in the diagnosis of malignant and benign OD.MethodsWe searched MEDLINE, EMBASE, EMBASE Classic and the Cochrane Library. A bivariate random‐effect model was used to calculate pooled diagnostic efficacy of AI models and endoscopists. The reference tests were histology for neoplasms and the clinical and instrumental diagnosis for gastro‐oesophageal reflux disease (GERD). The pooled area under the summary receiver operating characteristic (AUROC), sensitivity, specificity, positive and negative likelihood ratio (PLR and NLR) and diagnostic odds ratio (DOR) were estimated.ResultsFor the diagnosis of Barrett's neoplasia, AI had AUROC of 0.90, sensitivity 0.89, specificity 0.86, PLR 6.50, NLR 0.13 and DOR 50.53. AI models’ performance was comparable with that of endoscopists (P = 0.35). For the diagnosis of oesophageal squamous cell carcinoma, the AUROC, sensitivity, specificity, PLR, NLR and DOR were 0.97, 0.95, 0.92, 12.65, 0.05 and DOR 258.36, respectively. In this task, AI performed better than endoscopists although without statistically significant differences. In the detection of abnormal intrapapillary capillary loops, the performance of AI was: AUROC 0.98, sensitivity 0.94, specificity 0.94, PLR 14.75, NLR 0.07 and DOR 225.83. For the diagnosis of GERD based on questionnaires, the AUROC, sensitivity, specificity, PLR, NLR and DOR were 0.99, 0.97, 0.97, 38.26, 0.03 and 1159.6, respectively.ConclusionsAI demonstrated high performance in the clinical and endoscopic diagnosis of OD.

618 STUDY ON THE RELATIONSHIP BETWEEN GASTROESOPHAGEAL REFLUX SYMPTOMS AND ESOPHAGEAL MICROBIOTA

Abstract The occurrence of gastroesophageal reflux symptoms is related to the changes of esophageal mucosal sensitivity and esophageal motility. Studies have found that changes in gut microbiota can cause lower digestive tract symptoms by changing intestinal sensitivity and intestinal motility. The current study aimed to explore whether changes of esophageal microbiota can cause gastroesophageal reflux symptoms by altering esophageal sensitivity and esophageal motility. Methods Patients who were admitted to our hospital due to heartburn and reflux symptoms were prospectively included. Ten healthy volunteers and 10 patients with duodenal ulcer were included as controls. Both patients’ and healthy volunteers’ distal esophagus mucosal tissues and gastric fluid were collected under endoscopy for extraction of bacterial DNA. Patients and volunteers were divided into different groups according to disease situations, esophageal motility status, proton pump inhibitor (PPI) treatment efficacy. The α-diversity, β-diversity and specific composition of the microbiota among different groups were compared. Results A total of 12 patients with gastroesophageal reflux disease (G), 16 patients with functional esophageal disorder (F), 10 healthy volunteers (H), and 10 duodenal ulcer patients (D) were included. Esophageal mucosal microbiota analysis revealed that the microbiota composition was similar in patients with gastroesophageal reflux disease and functional esophageal disorders, which significantly different from that in healthy volunteers and patients with duodenal ulcers. Both gastroesophageal reflux disease patients and functional esophageal disorder patients had higher proportion of Pseudomonas than healthy controls and duodenal ulcer patients (G vs. F vs. H vs. D = 25.5% vs. 41.9% vs. 0.2% vs. 1.2%；P = 0.041). Conclusion The microbiota composition of patients with gastroesophageal reflux disease and patients with functional esophageal disorder were similar and were both significantly different from that of healthy volunteers and patients with duodenal ulcer. The increased proportion of Gram-negative bacteria such as Pseudomonas may play an important role in the occurrence of gastroesophageal reflux symptoms.

Zero-Heat-Flux and Esophageal Temperature Monitoring in Orthopedic Surgery: An Observational Study.

PurposePerioperative hypothermia prevention requires regular, accurate, and consistent temperature monitoring. Zero-heat-flux (ZHF) thermometry offers a non-invasive, measurement method that can be applied across all surgical phases. The purpose of this study was to measure agreement between the zero-heat-flux device and esophageal monitoring, sensitivity, and specificity to detect hypothermia and patient acceptability amongst patients undergoing upper and lower limb orthopedic surgery.Patients and MethodsThis prospective, observational study utilized Bland–Altman analysis and Lin’s concordance coefficient to measure agreement between devices, sensitivity and specificity to detect hypothermia and assessed patient acceptability amongst 30 patients between December 2018 and June 2019.ResultsBias was observed between devices via Bland Altman, with bias dependent on actual temperature. The mean difference ranged from −0.16°C at 34.9°C (where the mean of ZHF was lower than the esophageal device) to 0.46°C at 37.25°C (where the mean of ZHF was higher than esophageal device), with 95% limits of agreement (max) upper LOA = 0.80 to 1.41, lower LOA = −1.12 to −0.50. Seventy-five percentage of zero-heat-flux measurements were within 0.5°C of esophageal readings. Patient acceptability was high; 96% (n=27) stated that the device was comfortable.ConclusionZHF device achieved lesser measurement accuracy with core (esophageal) temperature compared to earlier findings. Nonetheless, due to continuous capability, non-invasiveness and patient reported acceptability, the device warrants further evaluation.Title RegistrationThe study was registered at www.ANZCTR.org.au (reference: ACTRN12619000842167).

Characterization of Esophageal and Sphincter Reflexes across Maturation in Dysphagic Infants with Oral Feeding Success vs Infants requiring Gastrostomy.

To test the hypothesis that esophageal and sphincteric sensory-motor reflexes are distinct across maturation in infants with dysphagia receiving gastrostomy-tube (G-tube). This is a retrospective review of 29 dysphagic infants (N = 15 study requiring gastrostomy, N = 14 age matched control achieving oral feeds) that underwent longitudinal pharyngeal-esophageal manometry at 42.3 (37-50.2) weeks postmenstrual age (PMA) and 48.9 (43.3-57.9) weeks PMA. Graded stimuli (0.1-5mL) of varying media (air, water, and apple juice) tested esophageal peristaltic reflex, upper esophageal sphincter contractile reflex (UESCR), and lower esophageal sphincter relaxation reflex (LESRR). Comparisons were performed between study and controls and across maturation (time-1 vs time-2). Data represented as mean ± SE or OR (95% CI). Across maturation (time-1 vs time-2): Study infants did not exhibit significant differences across in peristaltic, UES, or LES reflexes (all p > 0.05). In contrast, controls exhibited increased UES resting pressure (13 ± 3 vs 17 ± 3mmHg, p = 0.001), LES resting pressure (22 ± 3 vs 25 ± 3mmHg, p < 0.009), LES nadir pressure (0.5 ± 1 vs 4.3 ± 1mmHg, p = 0.001), and esophago-deglutition responses [2.5 (1.23-4.88), p = 0.04], and decreased secondary peristalsis [0.44 (0.31-0.61), p = 0.001], UESCR [0.4 (0.25-0.65), p = 0.001], LESRR [0.4 (0.24-0.75), p = 0.01], and symptoms [0.6(0.45-0.83), p = 0.005]. Among infants with dysphagia, esophageal provocation induced peristaltic reflex, UESCR, and LESRR advance with longitudinal maturation when infants are oral-fed successfully, but not in those who received gastrostomy. Underlying mechanisms may be related to esophageal sensitivity, afferent or efferent transmission, and coordination of upstream excitation and downstream inhibition, which can be potential therapeutic targets for improving feeding capabilities after gastrostomy placement in infants with dysphagia.

The role of serotonin in the control of esophageal sensitivity assessed by multimodal stimulation in health.

Esophageal hypersensitivity is considered an important pathophysiological mechanism in refractory gastroesophageal reflux disease (GERD) patients. Serotonin (5-HT) plays an important role in the regulation of GI (gastrointestinal) secretion, motility and sensitivity. Previous studies found that altered 5-HT availability has no clear effects on esophageal/GI sensations. Our aim was therefore to investigate the role of 5-HT in esophageal sensitivity in healthy volunteers (HV). Esophageal sensitivity to thermal, mechanical, electrical, and chemical stimuli was assessed in 3 different placebo-controlled studies. In the first study, the effect of citalopram (40mg; 5-HT reuptake inhibitor; intravenous) was investigated (n=14). In the second study, the effect of buspirone (20mg; 5HT1A agonist; oral) was investigated (n=10). In the third study, acute tryptophan depletion (ATD) was used to decrease 5-HT levels to investigate the effect of reduced 5-HT availability on esophageal sensitivity (n=15). No difference was observed in esophageal sensitivity after the administration of citalopram or buspirone (all p>0.06). In contrast, pain perception threshold to chemical stimulation was increased after ATD (p=0.017, Cohen's d+=0.67). No effect was found on the first perception or pain tolerance threshold. ATD had no influence on esophageal sensitivity to thermal, mechanical, and electrical stimulation compared with placebo. ATD, which induces 5-HT depletion, significantly decreased pain perception threshold during chemical stimulation, without affecting sensitivity to mechanical, thermal, or electrical stimulation. These findings confirm the involvement of 5-HT in the control of esophageal acid sensitivity, but identifying the receptors involved requires more ligands and studies.

Differentiating esophageal sensitivity phenotypes using pH-impedance in intensive care unit infants referred for gastroesophageal reflux symptoms.

OBJECTIVE:To identify esophageal sensitivity phenotypes relative to acid (SAcid), bolus (SBolus), acid and bolus (SAcid+Bolus), and none (SNone) exposures in infants suspected with gastroesophageal reflux disease (GERD).METHODS:Symptomatic infants (N=279) were evaluated for GERD at 42(40–45) weeks postmenstrual age using 24-hour pH-impedance. Symptom associated probability (SAP) for acid and bolus components defined esophageal sensitivity: 1) SAcid as SAP≥95% for acid (pH<4), 2) SBolus as SAP≥95% for bolus, 3) SAcid+Bolus as SAP≥95% for acid and bolus, or 4) SNone as SAP<95% for acid and bolus.RESULTS:Esophageal sensitivity prevalence (SAcid, SBolus, SAcid+Bolus, SNone) was 28(10%), 94(34%), 65(23%), and 92(33%) respectively. Emesis occured more in SBolus and SAcid+Bolus vs SNone (p<0.05). Magnitude (#/day) of cough and emesis events increased with SBolus and SAcid+Bolus vs SNone (p<0.05). SAcid+Bolus had increased acid exposure vs SNone (p<0.05). Distributions of feeding and breathing methods were distinct in infants with SBolus vs SNone (both, p<0.05). Multivariate analysis revealed that arching and irritability events/day were lesser at higher PMAs (p<0.001), greater for infants on NCPAP (p<0.01), with SBolus and SAcid+Bolus (p<0.05). Coughs/day was greater at higher PMAs (p<0.001), for infants with gavage and transitional feeding methods (p<0.02), with SBolus and SAcid+Bolus (p<0.05) but lesser with Trach (p<0.001). Number of emesis events/day were greater with SBolus and SAcid+Bolus (p<0.001). Sneezes/day decreased for infants on Trach (p=0.02).CONCLUSIONS:Feeding and breathing methods can influence the frequency and type of aerodigestive symptoms. We differentiated esophageal sensitivity phenotypes in NICU infants referred for GERD symptoms using pH-Impedance. Acid sensitivity alone was rare, which may explain poor response to acid suppressives; aerodigestive symptoms were predominantly linked with bolus spread. Magnitude of esophageal acid exposure and esophageal sensitivity to bolus spread may explain the pathophysiological basis for symptoms.

Esophageal acid sensitivity in patients with gastroesophageal reflux disease: Does esophageal hypomotility matter?

Esophageal acid sensitivity plays a role in symptomatic manifestation of gastroesophageal reflux disease (GERD). Esophageal hypomotility is common in patients with GERD. We aimed to determine whether esophageal acid sensitivity may differ between patients with and without esophageal hypomotility. We prospectively enrolled 41 consecutive patients (10 females, mean age 53years, range 32-79) with typical reflux symptoms and 10 healthy subjects (5 females, mean age 45years, range 28-56) for esophageal acid sensitivity and motility tests. Demographics, body mass index (BMI), and reflux symptoms using a validated questionnaire (GERDQ) were recorded. All subjects underwent infusion of 0.1N hydrochloric acid in the esophagus at a rate of 10mL/min for 10minutes. The parameters for esophageal acid infusion included lag time, intensity rating, and acid sensitivity score. Esophageal motility diagnosis included 24 patients with normal motility and 17 patients with ineffective esophageal motility (IEM). Lag time was similar between the patient groups. No differences between patients with normal motility and IEM were found for any of other acid infusion parameters. There was a positive correlation between lag time and BMI (r=.33, P=.04). GERDQ was negatively correlated to lag time (r=-.73, P<.001). Esophageal acid sensitivity was similar in GERD patients with and without hypomotility. Decreased acid sensitivity in individuals with increasing body mass index may play a pathological role in symptomatic modulation of patients with GERD.

Effect of citalopram on esophageal motility in healthy subjects-Implications for reflux episodes, dysphagia, and globus.

Drugs such as citalopram, "targeting" the serotonin pathway, can alter esophageal mechano-chemical sensitivity and gastrointestinal motility. The aim of this study was to clarify the effect of citalopram on esophageal motility and sphincter function, transient lower esophageal sphincter relaxations (TLESRs), and reflux events. Sixteen healthy volunteers (HV) receiving 20mg citalopram or placebo intravenously, in a randomized cross-over fashion, underwent two high-resolution impedance manometry studies involving liquid swallows and a high-fat, high-caloric meal. Manometric, reflux, and symptom-related parameters were studied. A lower distal contractile integral was recorded under citalopram, compared with placebo (P=0.026). Upper esophageal sphincter (UES) resting pressure was significantly higher after citalopram administration throughout the study (P<0.05, all periods). Similarly, the UES postswallow mean and maximum pressures were higher in the citalopram condition (P<0.0001, in both cases) and this was also the case for the 0.2s integrated relaxation pressure (P=0.04). Esophagogastric junction resting pressures in the citalopram visit were significantly higher during swallow protocol, preprandial period, and the first postprandial hour (P<0.05, in all cases). TLESRs and total reflux events were both reduced after citalopram infusion (P=0.01, in both cases). During treatment with citalopram, five participants complained about globus sensation (P=0.06). This citalopram-induced globus was associated with higher UES postswallow mean and maximum pressure values (P=0.01 and P=0.04, respectively). Administration of citalopram exerts a diversified response on esophageal motility and sphincter function, linked to clinically relevant phenomena: a reduction in postprandial TLESRs and the induction of drug-induced globus.

Tu1237 – Esophageal Acid Sensitivity in Patients with Gerd: Does Esophageal Hypomotility Matter?

Tu1237 – Esophageal Acid Sensitivity in Patients with Gerd: Does Esophageal Hypomotility Matter?

The effect of chronic restraint stress on esophageal visceral sensitivity and significance of stress-induced esophageal inflammation and oxidative stress in a murine model

Objective: To discuss the effect of chronic restraint stress (CRS) on esophageal hypersensitivity and inflammation, as well as the impact of oxidative stress in a murine model. Methods: 20 male SPF mice were randomly divided into two groups, CRS and normal control(NC) group. Then the mice in CRS group were submitted to 2 h per day of restraint stress for a period of 14 days. For the rest of the time, mice in both groups were given free drinking and eating in the same environment. Histopathological changes of esophageal tissue were observed using HE staining and analyzed by histological damaging score. The esophageal expression levels of transient receptor potential vanilloid (TRPV-1) and nicotinamide adenine dinucleotide phosphate oxidase 4(NOX-4) were detected by immunohistochemical staining. Further more, protein expression level of TRPV-1 was also observed by Western blotting. In addition, mRNA expression levels of TRPV-1, oxidant/antioxidant enzymes and related cytokines in esophageal tissues were detected by real time PCR. Results: HE staining for esophageal tissues revealed that histopathological changes including basal cell hyperplasia, infiltration of neutrophils and plasmocytes were observed in stressed mice, while there was no distinct changes observed in non-stressed mice. Histological damaging scores for epithelial damage and submucosal inflammatory cells were higher in CRS group, and the differences were statistically significant(all P<0.05). Immunohistochemical staining revealed that positive cells for TRPV-1 and NOX-4 were observed in majority of samples, but the number of positive cells and density were higher in CRS mice. Western blotting showed that the expression levels of TRPV-1 protein in CRS mice was higher than that of NC mice (1.0±0.0 vs 1.6±0.2; t=-7.06, P<0.001). RT-PCR showed that mRNA expression levels of TRPV1 and NOX-4 in CRS group were higher than those in NC group (1.0±0.0 vs 2.0±0.2, 1.0±0.0 vs 2.0±0.2; t=-13.44, -14.32, all P<0.001). Moreover, mRNA expression levels of antioxidant enzymes, such as Mn-SOD and Cu Zn-SOD, were higher in stressed mice (1.0±0.0 vs 0.7±0.1, 1.0±0.0 vs 0.7±0.1), and the differences were statistically significant (t=8.39,7.36, all P<0.05). The mRNA expression levels of important cytokines, such as MCP-1, IL-8, TNF-α, in stressed mice were overexpressed comparing to non-stressed mice (1.0±0.0 vs 2.4±0.4, 1.0±0.0 vs 1.8±0.2, 1.0±0.0 vs 2.5±0.4), and the differences were statistically significant (t=-10.06, -13.24, -12.40, all P<0.001). Conclusions: Chronic stress may result in esophageal hypersensitivity through activation of TRPV1, and may also cause esophageal inflammation. Stress-induced oxidative stress may contribute to the formation of esophageal hypersensitivity.

Management of gastroesophageal reflux disease: Patient and physician communication challenges and shared decision making.

Gastroesophageal reflux disease (GERD) is a common upper esophageal condition and typical symptoms can include heartburn and sensation of regurgitation while atypical symptoms include chronic cough, asthma, hoarseness, dyspepsia and nausea. Typically, diagnosis is presumptive given the presence of typical and atypical symptoms and is an indication for empiric therapy. Treatment management can include lifestyle modifications and/or medication therapy with proton pump inhibitor (PPI) class being the preferred and most effective. Complete symptom resolution is not always achieved and long-term PPI therapy can put patients at risk for serious side effects and needless expense. The brain-gut connection and hypervigilance plays an important role in symptom resolution and treatment success, especially in the case of non-PPI responders. Hypervigilance is a combination of increased esophageal sensory sensitivity in combination with exaggerated threat perception surrounding esophageal symptoms. Hypervigilance requires a different approach to GERD managements, where continued PPI therapy and surgery are usually not recommended. Rather, helping physicians and patients understand the brain-gut connection can guide and improve care. Education and reassurance should be the main pillars or treatment. However, it is important not to suggest the symptoms are due to anxiety alone, this often leads to patient dissatisfaction. Patient dissatisfaction with treatment reveals the need for a more patient-centered approach to GERD management and better communication between patients and providers. Shared decision making (SDM) with the incorporation of patient-reported outcomes (PRO) promotes patient adherence and satisfaction. SDM is a joint discussion between clinician and patient in which a mutually shared solution is explored for GERD symptoms. For SDM to work the physician needs to capture patients’ perceptions which may not be obtained in the standard interview. This can be done through the use of PROs which promote a dialogue with patients about their symptoms and treatment priorities in the context of the SDM patient encounter. SDM could potentially help in the management of patient expectations for GERD treatment, ultimately positively impacting their health-related quality of life.

Cough reflex sensitivity does not correlate with the esophageal sensitivity to acid in patients with gastroesophageal reflux disease

The sensitization of cough reflex observed in patients with gastroesophageal reflux disease (GERD) is attributed to activation of vagal C-fibers innervating the esophagus by acid, while the heartburn in GERD is mediated by esophageal acid sensitive C-fibers derived from (dorsal root ganglia) DRG. Here we explored the relationship between cough reflex sensitivity (CRS) and esophageal sensitivity to acid. We evaluated CRS to capsaicin inhalation and esophageal sensitivity to acid (intensity of heartburn evoked by esophageal infusions of acid pH = 3, 2 and 1) in patients with GERD and chronic heartburn before and 3 months after proton pump inhibitor (PPI) treatment. There was no correlation between CRS and esophageal sensitivity to acid at any pH tested. PPI treatment substantially reduced esophageal sensitivity to acid but did not affect CRS. We conclude that a simple direct relationship between CRS and esophageal sensitivity to acid is unlikely. The results indicate that spinal and vagal afferent pathways from the esophagus are probably influenced separately in subjects with GERD.

Intravenous Corticotropin-releasing Hormone Administration Increases Esophageal Electrical Sensitivity in Healthy Individuals.

Background/AimsWhen a person is experiencing stress, corticotropin-releasing hormone (CRH) can modulate gut physiologies, such as visceral sensation or gastrointestinal motility, and its intravenous administration mimics stress-induced physiological changes. However, the influence of CRH on the esophagus is yet unknown. Accordingly, we investigated whether intravenous CRH administration increases esophageal sensitivity to electrical stimulation in healthy Japanese subjects.MethodsTwenty healthy subjects were recruited. We quantified the initial perception threshold (IPT) every 15 minutes after CRH injection. Venous blood was collected with a cannula, and both plasma adrenocorticotropic hormone (ACTH) and cortisol were measured at pre-stimulation, 0, 30, 60, 90, and 120 minutes. The results from each time point were compared against a baseline IPT obtained before electrical stimulation was initiated.ResultsWhen compared to the baseline IPT value (16.9 ± 4.5), CRH significantly decreased electrical threshold of the esophagus at 30, 45, 60, 75 minutes (14.1 ± 4.2, 13.1 ± 5.0, 12.1 ± 5.7, 14.0 ± 5.8 minutes, P < 0.01, respectively) after CRH injection, suggesting that CRH increased esophageal sensitivity to the electrical stimulus. CRH also significantly increased plasma ACTH levels at 30 minutes (50.3 ± 17.7, P < 0.01), and cortisol levels at 30 minutes (22.0 ± 6.7 minutes, P < 0.01) and 60 minutes (20.3 ± 6.7 minutes, P < 0.01) after CRH injection, when compared to the pre-stimulation ACTH and cortisol values.ConclusionIntravenous CRH administration increased esophageal electrical sensitivity in normal subjects, emphasizing the important role of stress in esophageal sensitivity.