Frequency of functional esophageal disorders in patients with refractory reflux symptoms in Lima, Peru

Gastroesophageal reflux disease (GERD) is a clinical condition in which gastric reflux causes symptoms or damage to the esophageal mucosa. It is managed with proton pump inhibitors, however, up to 45% of patients with suspected GERD are refractory to treatment. It is necessary to establish a true GERD diagnosis by means of a digestive endoscopy, which does not show lesions in approximately 70% of patients. In this scenario, it is necessary to perform an esophageal pH-impedance measurement, a procedure that allows to determine whether exposure to gastric acid is pathological. Of this group, patients with pathological acid exposure are diagnosed as true non-erosive reflux disease (NERD). If, in addition to not presenting esophageal lesions, they have a physiological exposure to gastric acid, they suffer from esophageal hypersensitivity or functional heartburn, which are functional disorders. These require a different approach from that of GERD or NERD, as the symptoms are not due to pathological exposure to gastric acid. The aim was to calculate the frequency of esophageal hypersensitivity and functional heartburn in patients with suspected NERD. This was a cross-sectional study. Data was collected by reviewing pH-impedance and manometry reports, 166 patients were selected. The frequency for functional disorders was 86.15%, being 46.9% for functional heartburn and 39.2% for esophageal hypersensitivity. The frequency of functional disorders was higher than that reported in previous studies. In conclusion, age, psychological conditions, dietary, cultural, ethnic or lifestyle factors inherent to our environment might play important roles in the development of functional disorders.

La enfermedad por reflujo gastroesofágico (ERGE) es una condición clínica en la que el reflujo gástrico provoca síntomas o daños en la mucosa esofágica. Se maneja con inhibidores de la bomba de protones; sin embargo, hasta el 45% de los pacientes con sospecha de ERGE son refractarios al tratamiento. Por lo cual, es necesario establecer un verdadero diagnóstico de ERGE mediante una endoscopia digestiva, que no muestra lesiones en aproximadamente el 70% de los pacientes. En este escenario, es necesario realizar una medición de pH-impedancia esofágica, procedimiento que permite determinar si la exposición al ácido gástrico es patológica. De este grupo, los pacientes con exposición patológica al ácido son diagnosticados como verdadera enfermedad por reflujo no erosiva (ERNE). Si además de no presentar lesiones esofágicas, tienen una exposición fisiológica al ácido gástrico, padecen hipersensibilidad esofágica o pirosis funcional, que son trastornos funcionales. Estos requieren un enfoque diferente al ERGE o ERNE, ya que los síntomas no se deben a una exposición patológica al ácido gástrico. El objetivo fue calcular la frecuencia de hipersensibilidad esofágica y pirosis funcional en pacientes con sospecha de ERNE. Este fue un estudio transversal. Los datos se recopilaron mediante la revisión de informes de pH-impedancia y manometría, se seleccionaron 166 pacientes. La frecuencia de trastornos funcionales fue de 86,15%, siendo 46,9% de pirosis funcional y 39,2% de hipersensibilidad esofágica. La frecuencia de trastornos funcionales fue superior a la reportada en estudios previos. En conclusión, la edad, las condiciones psicológicas, los factores dietéticos, culturales, étnicos o de estilo de vida inherentes a nuestro entorno podrían jugar un papel importante en el desarrollo de trastornos funcionales.

Characteristics of reflux and manifestation under probe-based confocal laser endoscopy in patients with endoscopic negative heartburn / 中华消化内镜杂志

Objective:To study reflux characteristics of patients with endoscopic negative heartburn and their manifestation under probe-based confocal laser endoscopy (pCLE) based on the Rome Ⅳ standard.Methods:Thirty-six endoscopic negative outpatients with typical heartburn at the Department of Gastroenterology of the Second Affiliated Hospital of Baotou Medical College from September 2020 to March 2021 were included, and underwent 24-hour multichannel intraluminal impedance-pH monitor and pCLE. According to Rome Ⅳ diagnostic process, patients were divided into non-erosive reflux disease (NERD) group ( n=16), reflux hypersensitivity (RH) group ( n=8) and functional heartburn (FH) group ( n=12). The Gerd-Q scale score, 24-hour pH monitoring results and microstructure changes under pCLE were compared among the three groups. Results:There was no significant difference in the total score, positive symptom score, negative symptom score or positive influence score of Gerd-Q scale among the three groups ( P>0.05). DeMeester score [28.45 (20.08, 34.53)] and acid reflux times (24.88±9.05) in the NERD group were significantly higher than those in the RH group [7.30 (3.90, 11.38), P<0.001; 13.63±5.76, P=0.003] and FH group [6.90 (4.80, 9.73), P<0.001; 7.42±8.32, P<0.001]. But there was no significant difference between the RH group and the FH group ( P>0.05). The diameter of intra-papillary capillary loop (IPCL) (18.68±2.12 μm) and dilation of intercellular space (3.95±0.97 μm) in the NERD group were significantly higher than those in the RH group (13.91±1.99 μm, P<0.001; 2.97±0.55 μm, P=0.006) and FH group (13.83±2.00 μm, P<0.001; 2.31±0.54 μm, P<0.001), but there was no significant difference between the RH group and the FH group ( P>0.05). The number of IPCL in the NERD group, RH group and FH group were 2.0 (1.00, 2.75), 2.0 (1.00, 2.75) and 1.5 (1.00, 2.00), respectively with no significant difference ( P=0.697). Conclusion:Gerd-Q scale is not suitable for differential diagnosis of patients with endoscopic negative heartburn. Compared with functional esophageal diseases (RH and FH), acid reflux and mucosal microstructure changes are of more important pathogenic significance in NERD.

Functional Changes of the Upper Esophageal Sphincter in Gastroesophageal Reflux

Abstract Introduction The upper esophageal sphincter (UES) is a muscular structure located at the transition from the pharynx to the esophagus, with the cricopharyngeal muscle as the most important component. During gastroesophageal reflux, the pressure in the UES elevates, which is apparently a protective mechanism to prevent esophagopharyngeal reflux and airway aspiration. In gastroesophageal reflux disease (GERD), there may be functional changes in the UES. Objective The objective of the present review was to determine UES functional changes in GERD. Data Synthesis In healthy individuals, gastroesophageal reflux causes an increase in the UES pressure. This response of the sphincter is at least partially impaired in patients with GERD. In the disease, the UES has a reduced length and decreased resting pressure. However, other publications found that in chronic gastroesophageal reflux the basal sphincter pressure increase, differences which may be consequent to the measurement method or to disease severity. The UES opening during swallowing has a smaller diameter, and the bolus transit time through the sphincter is longer. Conclusion The UES of patients with GERD does not open as expected and the bolus flow through the sphincter is longer. This behavior may be associated with dysphagia, a frequent complaint in patients with GERD.

Correlação entre sintomas e refluxo em pacientes com doença do refluxo gastroesofágico / Correlation between symptoms and reflux in patients with gastroesophageal reflux disease

ABSTRACT Background: Esophageal symptoms of gastroesophageal reflux are the same in functional heartburn, non-erosive disease, and erosive disease. Their patient-perceived intensity may be related to gastroesophageal reflux intensity. Objective To evaluate whether the symptoms in GERD patients are related to the intensity of gastroesophageal acid reflux. Methods To test this hypothesis, 68 patients with heartburn (18 with functional heartburn, 28 with non-erosive reflux disease, and 22 with erosive reflux disease) had their symptoms evaluated by the Velanovich score (which mainly focuses on heartburn) and the Eating Assessment Tool (EAT-10) (which focuses on dysphagia). They were submitted to esophageal endoscopy and then, on another day, they answered the Velanovich and EAT-10 questionnaires and underwent manometry and 24-hour pHmetry (measured 5 cm proximal to the upper border of the lower esophageal sphincter). Results The Velanovich score was higher in patients with non-erosive and erosive diseases than in those with functional heartburn. The mean EAT-10 score did not differ between functional heartburn, erosive, and non-erosive gastroesophageal reflux disease. Considering the threshold of ≥5 to define dysphagia, 4 (22%) patients with functional heartburn, 12 (43%) with non-erosive disease, and 9 (41%) with erosive disease had dysphagia (P=0.18). There was: a) a moderate correlation between the Velanovich and DeMeester score and between Velanovich score and the percentage of acid exposure time (AET); b) a weak correlation between EAT-10 and DeMeester score and between EAT-10 and acid exposure time. Conclusion: There is a moderate positive correlation between heartburn and gastroesophageal reflux measurement. Dysphagia has a weak positive correlation with reflux measurement.

RESUMO Contexto Os sintomas esofágicos do refluxo gastroesofágico são os mesmos na pirose funcional, doença do refluxo não erosiva e doença erosiva. A intensidade percebida pelo paciente pode estar relacionada à intensidade do refluxo gastroesofágico. Objetivo Avaliar se os sintomas em pacientes com doença do refluxo gastroesofágico estão relacionados à intensidade do refluxo. Métodos: Sessenta e oito pacientes com pirose (18 com pirose funcional, 28 com doença do refluxo não erosiva e 22 com doença erosiva) tiveram seus sintomas avaliados pelo escore de Velanovich (que avalia principalmente pirose) e o Instrumento de Autoavaliação da Alimentação (EAT-10) (que avalia disfagia). Os pacientes foram submetidos à endoscopia esofágica e, em outro dia, responderam aos questionários Velanovich e EAT-10 e realizaram manometria e pHmetria de 24 horas (medida 5 cm proximal à borda superior do esfíncter esofágico inferior). Resultados O escore de Velanovich foi maior em pacientes com doença não erosiva e doença erosiva do que naqueles com pirose funcional. A pontuação média da EAT-10 não diferiu entre pirose funcional, doença do refluxo gastroesofágico erosiva e não erosiva. Considerando o limiar ≥5 para definir disfagia, 4 (22%) pacientes com pirose funcional, 12 (43%) com doença não erosiva e 9 (41%) com doença erosiva apresentavam disfagia (P=0,18). Houve: a) correlação moderada entre os escores de Velanovich e DeMeester e entre os escores de Velanovich e o percentual de tempo de exposição ao ácido (AET); b) uma correlação fraca entre o EAT-10 e o escore DeMeester e entre o EAT-10 e o tempo de exposição ao ácido. Conclusão Existe uma correlação positiva moderada entre a pirose e a medida do refluxo gastroesofágico. Disfagia tem correlação fraca com a medição do refluxo.

Clinical significance of ineffective esophageal motility in non-erosive acid reflux diseases / 中华消化内镜杂志

Objective:To investigate the role of ineffective esophageal motility (IEM) in non-erosive acid reflux related diseases, and the influence of the fourth edition Chicago classification (CC v4.0) on the diagnosis of IEM.Methods:From January 2018 to January 2020, 63 patients with acid reflux related symptoms who underwent gastroscopy and showed no abnormal changes in esophageal mucosa or structure, and underwent high resolution esophageal manometry (HRM) and 24-hour esophageal pH monitoring in the Department of Gastroenterology of Beijing Friendship Hospital were included in the case-control study. According to the HRM results, the third edition Chicago classification standard (CC v3.0) and CC v4.0 were used to divided patients into IEM group and normal dynamic group. The HRM results, 24-hour esophageal pH monitoring results and final diagnosis of the two groups under the two editions of Chicago classification standard were mainly compared and analyzed.Results:Among the 63 patients, there were 14 cases of non-erosive gastroesophageal reflux disease (NERD), 19 cases of reflux hypersensitivity (RH), and 30 cases of functional heartburn (FH). When using CC v3.0, there were 20 cases in the IEM group, including 9 cases of NERD, 5 cases of RH and 6 cases of FH, and 43 cases in the normal dynamic group, including 5 cases of NERD, 14 cases of RH and 24 cases of FH. When using CC v4.0, there were 16 cases in the IEM group, including 7 cases of NERD, 4 cases of RH and 5 cases of FH, and 47 cases in the normal dynamic group, including 7 cases of NERD, 15 cases of RH and 25 cases of FH. When using CC v3.0, compared with the normal dynamic group, the acid exposure time (AET) of the IEM group was significantly higher [3.45 (1.55, 6.40)% VS 1.20 (0.40, 2.30)%, Z=-2.940, P=0.003], the DeMeester score was also significantly higher [13.8 (5.8, 21.4) VS 5.3 (2.9, 10.0), Z=-2.851, P=0.004], the lower esophageal sphincter pressure (LESP) [10.15 (7.52, 13.65) mmHg (1 mmHg=0.133 kPa) VS 15.40 (11.20, 21.60) mmHg, Z=-3.241, P=0.001], 4-second integrated relaxation pressure (4sIRP) (3.79±0.57 mmHg VS 6.05±0.50 mmHg, t=2.727, P=0.008), and distal contraction integral (DCI) [334.65 (208.25, 438.92) mmHg·s·cm VS 1 258.70 (919.00, 1 750.10) mmHg·s·cm, Z=-6.305, P<0.001] were significantly lower than those of the normal dynamic group. When using CC v4.0, AET and Demeester scores in the IEM group were also significantly higher than those in the normal dynamic group (both P<0.05), and LESP, 4sIRP and DCI were also significantly lower than those in the normal dynamic group (all P<0.05). In addition, upper esophageal sphincter pressure was significantly lower than that in normal dynamic group [34.60 (21.50, 48.05) mmHg VS 49.67 (36.75, 61.10) mmHg, Z=-2.140, P=0.032]. Conclusion:IEM is associated with impaired anti-reflux barrier function and esophageal acid exposure in patients with non-erosive acid reflux related diseases. Compared with CC v3.0, CC v4.0 can reduce the heterogeneity of IEM patients to some extent.

Role of Esophageal Sensory Receptor Pathways in Development of Esophageal Hypersensitivity / 胃肠病学

Gastroesophageal reflux disease (GERD) is a common digestive disease characterized by heartburn and acid reflux. In recent years, many studies have shown that esophageal hypersensitivity is an important pathophysiological mechanism involved in the occurrence and development of heartburn. Esophageal sensory receptors including transient receptor potential vanilloid 1 (TRPV1), prostaglandin E

Comparison of esophageal motility and reflux characteristics of patients with endoscopic-negative heartburn based on the Lyon Consensus / 西安交通大学学报(医学版)

【Objective】 To explore the characteristics of esophageal motility and reflux of endoscopic-negative heartburn patients based on the Lyon Consensus Diagnostic Criteria and discuss the differential diagnosis value of the mean nocturnal baseline impedance （MNBI） and the postreflux swallow-induced peristaltic wave （PSPW） index for reflux hypersensitivity （RH） and functional heartburn （FH） patients. 【Methods】 We enrolled 132 patients with heartburn as the main symptom who visited the Gastroenterology Department of our hospital from January 2017 to June 2021， including 24 in the non-erosive reflux disease （NERD） group， 24 in the RH group， and 84 in the FH group. All the patients completed gastroscopy， esophageal high-resolution manometry and 24h-pH impedance monitoring. We analyzed and compared the related indexes of esophageal motility and reflux. The receiver operating characteristic （ROC） curve was used to analyze the esophageal proximal MNBI， distal MNBI， and PSPW indexes for the differential diagnosis of RH and FH. 【Results】 The lower esophageal sphincter （LES） average resting pressure， LES residual pressure and intact relaxation pressure （IRP） in NERD were lower than those in RH and FH （P0.05）. When the proximal MNBI， distal MNBI， and PSPW indexes were used alone respectively to diagnose RH， the area under the ROC curve was 0.480， 0.810， 0.682， respectively， with the sensitivities being 87.5%， 100% and 91.7%， and the specificities being 26.2%， 66.7% and 51.2%， respectively. 【Conclusion】 NERD patients have obvious abnormal esophageal dynamics， mainly manifested as LES relaxation， which further aggravates the pathological acid reflux， while patients with RH and FH are mainly exposed to physiological acid or non-acid reflux. In patients with endoscopic negative heartburn， distal MNBI value can improve the clinical diagnosis rate of RH and help distinguish RH from FH.

Impacto da pirose e regurgitação no bem-estar de indivíduos da população geral: um inquérito nacional brasileiro / Impact of heartburn and regurgitation on individuals' well-being in the general population: a brazilian national survey

ABSTRACT BACKGROUND: Heartburn and acid regurgitation are typical symptoms usually associated with gastroesophageal reflux disease (GERD). GERD is one of the gastrointestinal diagnosis with higher prevalence worldwide, significantly impairing patients' quality of life. OBJECTIVE: The objective of this study was to analyze the impact of GERD-related symptoms in the Brazilian urban population. METHODS: National telephone survey with community-dwelling Brazilian individuals. Self-reported prevalence and frequency of symptoms (heartburn / regurgitation) were assessed. Individuals rated the impact of symptoms in their general well-being using a numeric scale from 1 to 10 (1 = no impact; 10 = very intense, preventing the person to eat and perform daily routine activities). Descriptive and bivariate statistical analyses were performed. RESULTS: The final sample was comprised of 1,773 subjects, 935 (52.7%) females, an average of 40 years old. The prevalence of heartburn and regurgitation in the past 6 months was 26.2% (n=466) and 11.0% (n=196), respectively. Women presented higher prevalence (heartburn n=266, 28.5% and regurgitation n=119, 12.7%) than men (n=200, 23.1% and n=78, 8.9%, respectively) (P<0.05). Heartburn in the past week was reported by 175 individuals (9.8%), while regurgitation episodes by 67 (3.8%). Absence of impact of the symptom in the overall well-being was observed for 82 subjects (17.6%) with heartburn and 18 individuals (9.2%) with regurgitation. Very intense impact was reported by 46 subjects (9.8%) with heartburn and 41 (20.9%) with regurgitation. Women's well-being was more affected than men's (mean score 5.45 vs 4.71, P<0.05). CONCLUSION: Heartburn and regurgitation were frequent symptoms, women with higher prevalence. These symptoms led to a substantial impact on individuals' well-being, women being more affected.

RESUMO CONTEXTO: Pirose e regurgitação ácida são sintomas típicos usualmente relacionados à doença do refluxo gastroesofágico (DRGE). A DRGE é um dos diagnósticos gastrointestinais com maior prevalência mundial, afetando significativamente a qualidade de vida dos pacientes. OBJETIVO: Analisar o impacto de sintomas relacionados à DRGE em uma amostra da população brasileira urbana. MÉTODOS: Inquérito nacional via telefone com indivíduos brasileiros em contexto comunitário. O inquérito foi conduzido entre 6 de agosto e 12 de setembro de 2018. A prevalência autorrelatada e a frequência dos sintomas foram avaliadas. Os respondentes classificaram o impacto dos sintomas no seu bem-estar geral utilizando uma escala numérica de 1 a 10 (1 = ausência de impacto; 10 = impacto muito grave, impedindo a pessoa de comer ou realizar atividades da vida diária). Análises estatísticas descritivas e bivariadas foram conduzidas. RESULTADOS: A amostra final foi constituída por 1.773 indivíduos, 935 (52,7%) mulheres, com idade média de 40 anos. A prevalência de pirose e regurgitação nos últimos 6 meses foi de 26,2% (n=466) e 11,0% (n=196), respectivamente. Sexo feminino (pirose n=266, 28,5% e regurgitação n=119, 12,7%) apresentou prevalência mais alta do que o masculino (n=200, 23,1% e n=78, 8,9%, respectivamente) (P<0,05). Pirose na última semana foi relatada por 175 indivíduos (9,8%), enquanto episódios de regurgitação por 67 (3,8%). Ausência de impacto dos sintomas no bem-estar geral dos indivíduos foi observada para 82 respondentes (17,6%) com pirose e 18 (9,2%) daqueles com regurgitação. Impacto muito grave foi reportado por 46 (9,8%) indivíduos com pirose e 41 (20,9%) com regurgitação. Sexo feminino foi mais afetado pelos sintomas do que o masculino. CONCLUSÃO: Pirose e regurgitação foram bastante frequentes sendo o sexo feminino mais afetado. Tais sintomas levaram a impacto no bem-estar dos indivíduos, com maior prejuízo para mulheres.

Trânsitos oral e faríngeo na pirose funcional / Oral and pharyngeal transit in functional heartburn

ABSTRACT BACKGROUND: Gastroesophageal reflux disease is associated with slower transit of the bolus through the pharynx and upper esophageal sphincter. Functional heartburn has similar symptoms to gastroesophageal reflux disease, however, the symptoms are not caused by reflux. OBJECTIVE: The aim of this investigation was to evaluate oral and pharyngeal transit in patients with functional heartburn, with the hypothesis that, similar to patients with gastroesophageal reflux disease, they have changes in pharyngeal and upper esophageal sphincter transit time. METHODS: Oral and pharyngeal transit was evaluated by videofluoroscopy in eight women with functional heartburn, five with mild dysphagia for solid foods, and 12 female controls. Controls and patients swallowed in duplicate 5 mL and 10 mL of liquid and paste boluses. RESULTS: No difference in the oral or pharyngeal transit time was found between patients and controls. No aspiration of bolus into the airways was detected in any individual. Pharyngeal residues were detected in the same proportion of swallows, in patients (12.5%) and controls (15.0%), after swallows of 10 mL paste bolus. CONCLUSION: Oral, pharyngeal and upper esophageal sphincter transit time are similar in patients with functional heartburn to healthy controls.

RESUMO CONTEXTO: A doença do refluxo gastroesofágico está associada ao trânsito mais lento do bolo deglutido pela faringe e esfíncter superior do esôfago. Pirose funcional tem sintomas similares aos de doença do refluxo gastroesofágico, entretanto eles não são consequência de refluxo. OBJETIVO: Como na pirose funcional os sintomas são semelhantes aos da doença do refluxo gastroesofágico, o objetivo desta investigação foi avaliar a duração do trânsito do bolo deglutido pela boca, faringe e esfíncter superior do esôfago em pacientes com pirose funcional, com a hipótese de que esses pacientes também apresentem alteração no trânsito. MÉTODOS: Pelo método videofluoroscópico foi avaliado o trânsito oral e faríngeo de oito pacientes do sexo feminino com pirose funcional, cinco com disfagia leve para alimentos sólidos, e 12 indivíduos controles do sexo feminino. Controles e pacientes deglutiram em duplicata 5 mL e 10 mL de bolos com a consistências líquida e pastosa. RESULTADOS: Com bolo líquido e pastoso não houve diferença na duração do trânsito oral, faríngeo e pelo esfíncter superior do esôfago entre controles e pacientes. Não houve aspiração do bolo para as vias aéreas em nenhum indivíduo. Os resíduos faríngeos foram observados na mesma proporção das deglutições em pacientes (12,5%) e controles (15%), com a deglutição de 10 mL de bolo pastoso. CONCLUSÃO: A duração do trânsito oral, faríngeo e pelo esfíncter superior do esôfago foi semelhante nos pacientes com pirose funcional e controles.

Esophageal pH-impedance monitoring of reflux patterns in non-erosive reflux disease, reflux hypersensitivity and functional heartburn / 南方医科大学学报

OBJECTIVE@#To analyze the differences in reflux patterns in 24-hour esophageal pH-impedance monitoring in patients with non-erosive reflux disease (NERD), reflux hypersensitivity (RH) and functional heartburn (FH) and explore the possible mechanism of symptoms in patients with heartburn and negative endoscopic findings.@*METHODS@#Seventy-nine patients with heartburn as the main symptoms but negative endoscopic findings, including 35 with NERD, 16 with RH and 28 with FH, were enrolled in this study.All the patients underwent 24-h esophageal pH-impedance monitoring and esophagogastroscopy, and the results were compared among the 3 groups.@*RESULTS@#Acid reflux episode was significantly increased and weakly alkaline reflux episode was significantly decreased in NERD group in comparison with RH group and FH group (@*CONCLUSIONS@#Patients with NERD, RH and FH had different reflux patterns.Acid reflux is predominant in the NERD, while weakly alkaline reflux is significantly increased RH and FH.In patients with normal esophageal acid exposure but without symptoms or without recorded symptoms during esophageal pH-impedance monitoring, analysis of the total reflux episode, mixed reflux episode, proximal acid reflux episode and percentage can help in the differential diagnosis between RH and FH.

Prevalence of non-obstructive dysphagia in patients with heartburn and regurgitation

OBJECTIVE: Heartburn and regurgitation are the most common gastroesophageal reflux symptoms, and dysphagia could be a possible symptom. This investigation aimed to evaluate the prevalence of non-obstructive dysphagia in patients with heartburn and regurgitation. METHODS: A total of 147 patients (age, 20-70 years; women, 72%) complaining of heartburn and regurgitation, without esophageal stricture, previous esophageal surgery, or other diseases, were evaluated. Twenty-seven patients had esophagitis. The Eating Assessment Tool (EAT-10) was employed to screen for dysphagia; EAT-10 is composed of 10 items, and the patients rate each item from 0 to 4 (0, no problems; 4, most severe symptom). Results of the 147 patients were compared with those of 417 healthy volunteers (women, 62%; control group) aged 20-68 years. RESULTS: In the control group, only two (0.5%) had an EAT-10 score ≥5, which was chosen as the threshold to define dysphagia. EAT-10 scores ≥5 were found in 71 (48.3%) patients and in 55% of the patients with esophagitis and 47% of the patients without esophagitis. This finding indicates a relatively higher prevalence of perceived dysphagia in patients with heartburn and regurgitation and in patients with esophagitis. We also found a positive correlation between EAT-10 scores and the severity of gastroesophageal reflux symptoms based on the Velanovich scale. CONCLUSION: In patients with heartburn and regurgitation symptoms, the prevalence of dysphagia was at least 48%, and has a positive correlation with the overall symptoms of gastroesophageal reflux.

Study on esophageal motility and anti-reflux barrier function in patients with heartburn symptom and negative endoscopic findings based on Rome Ⅳ criteria / 中华消化杂志

Objective@#To evaluate esophageal motility and anti-reflux barrier function in patients with different phenotypes of heartburn and negative endoscopic findings based on the Rome Ⅳ criteria.@*Methods@#From March 2011 to November 2018, 136 patients with heartburn and negative endoscopic findings were retrospectively analyzed. The patients underwent high-resolution manometry (HRM), 24-hour pH monitoring and proton pump inhibitor (PPI) test and according to the Rome Ⅳ criteria and new diagnostic procedures, they were divided into non-erosive reflux disease (NERD) group, reflux hypersensitivity (RH) group, functional heartburn (FH) group and unclassified group. During the same period, 20 healthy volunteers were selected as healthy control group. The changes of esophageal motility and HRM were analyzed among different groups. Statistical analysis was performed using one-way analysis of variance, Kruskal-Wallis H test and chi-square test.@*Results@#According to Rome Ⅳ criteria, 35 patients were enrolled into the NERD group, 43 patients were enrolled into the RH group, 48 patients were included in the FH group, and 10 patients were enrolled into unclassified group. There were no significant differences between the NERD group, the RH group, the FH group, the unclassified group and healthy control group in the length of the lower esophageal sphincter (LES), end lower esophageal sphincter resting pressure (LESP), mean LESP, 4-second-integrated relaxation pressure (4 s-IRP), distal latency (DL) , upper esophageal sphincter residual pressure (UES-RP), upper esophageal sphincter relaxation time to nadir, upper esophageal sphincter (UES) recovery time and esophagogastric junction contractile integral (EGJ-CI, all P>0.05). The distal contractile integral (DCI) of NERD group and unclassified group were both lower than that of healthy control group (919.7 mmHg·s·cm (411.7, 1 417.9) mmHg·s·cm (1 mmHg=0.133 kPa), 535.6 mmHg·s·cm (321.4, 1 513.4) mmHg·s·cm vs. 1 322.1 mmHg·s·cm (841.6, 1 918.5) mmHg·s·cm), and the differences were statistically significant (Z=-2.62 and -2.20, P=0.01 and 0.03). The upper esophageal sphincter pressure (UESP) of the unclassified group was lower than that of the healthy control group(57.0 mmHg (31.3, 77.8) mmHg vs. 70.4 mmHg (49.4, 97.8) mmHg), and the difference was statistically significant (Z=-2.64, P=0.02). There was significant difference in esophagogastric junction (EGJ) subtypes between the NERD group, the RH group, the FH group and the unclassified group (χ2=10.85, P=0.02); the proportion of type Ⅲ patients was highest in unclassified group, followed by NERD group, which were both higher than those of RH group and FH group. There was no significant difference in the proportion of esophageal motility subtypes between NERD group, RH group, FH group and unclassified group (P>0.05).@*Conclusions@#Patients with different phenotypes of heartburn and negative endoscopy finding should be classified by efficient diagnostic procedure according to the Rome Ⅳ criteria combined with HRM, 24-hour pH monitoring and PPI test. The unclassified patients need further evaluation, especially for those with effective PPI test and negative pH monitoring. However, the evaluation of anti-reflux barrier function by the HRM parameters in patients with heartburn and negative endoscopic findings has certain limitations.

Role of Esophageal Mean Nocturnal Baseline Impedance and Post-reflux Swallow-induced Peristaltic Wave Index in Discriminating Chinese Patients With Heartburn

BACKGROUND/AIMS: Recently, esophageal mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave (PSPW) index have been proposed, which can increase the diagnostic role of multichannel intraluminal impedance and pH recording (MII/pH) for differentiating patients with heartburn. Therefore, our aim is to investigate the role of esophageal proximal MNBI, distal MNBI, and PSPW index in differentiating Chinese patients with heartburn. METHODS: Patients with heartburn from the Beijing Anzhen Hospital, who underwent upper gastrointestinal endoscopy and 24-hour MII/pH, were enrolled in this study. RESULTS: In all, 24 erosive esophagitis (EE), 46 non-erosive reflux disease (NERD), 52 reflux hypersensitivity (RH), and 78 functional heartburn (FH) patients were recruited. The respective median values for the EE, NERD, RH, and FH groups were as follows: proximal MNBI 1858.0, 2147.5, 2374.3, and 2329.0 Ω (P = 0.053); distal MNBI 1243.4, 1506.5, 2451.2, and 2477.3 Ω (P < 0.001); and PSPWI 15.0%, 25.0%, 25.0%, and 45.0% (P < 0.001). Spearman correlation analysis showed that distal MNBI and PSPW index were significantly negatively correlated with acid and bolus exposure time and acid reflux events. Receiver operating characteristic analyses showed that distal MNBI and PSPW index significantly discriminated FH from EE, NERD, and RH (P < 0.001), with cut-off values of 1890.6 Ω and 27.5% and areas under the curve of 0.721 and 0.779, respectively. CONCLUSION: Esophageal distal MNBI and PSPW index could increase the diagnostic role of MII/pH, especially for differentiating Chinese patients with heartburn.

Study on esophageal motility and anti-reflux barrier function in patients with heartburn symptom and negative endoscopic findings based on Rome Ⅳ criteria / 中华消化杂志

Objective To evaluate esophageal motility and anti-reflux barrier function in patients with different phenotypes of heartburn and negative endoscopic findings based on the Rome Ⅳ criteria.Methods From March 2011 to November 2018,136 patients with heartburn and negative endoscopic findings were retrospectively analyzed.The patients underwent high-resolution manometry (HRM),24-hour pH monitoring and proton pump inhibitor (PPI) test and according to the Rome Ⅳ criteria and new diagnostic procedures,they were divided into non-erosive reflux disease (NERD) group,reflux hypersensitivity (RH) group,functional heartburn (FH) group and unclassified group.During the same period,20 healthy volunteers were selected as healthy control group.The changes of esophageal motility and HRM were analyzed among different groups.Statistical analysis was performed using one-way analysis of variance,Kruskal-Wallis H test and chi-square test.Results According to Rome Ⅳ criteria,35 patients were enrolled into the NERD group,43 patients were enrolled into the RH group,48 patients were included in the FH group,and 10 patients were enrolled into unclassified group.There were no significant differences between the NERD group,the RH group,the FH group,the unclassified group and healthy control group in the length of the lower esophageal sphincter (LES),end lower esophageal sphincter resting pressure (LESP),mean LESP,4-second-integrated relaxation pressure (4 s-IRP),distal latency (DL),upper esophageal sphincter residual pressure (UES-RP),upper esophageal sphincter relaxation time to nadir,upper esophageal sphincter (UES) recovery time and esophagogastric junction contractile integral (EGJ-CI,all P ＞0.05).The distal contractile integral (DCI) of NERD group and unclassified group were both lower than that of healthy control group (919.7 mmHg · s · cm (411.7,1 417.9) mmHg· s · cm (1 mmHg =0.133 kPa),535.6 mmHg · s · cm (321.4,1 513.4) mmHg · s · cm vs.1 322.1 mmHg · s · cm (841.6,1 918.5) mmHg · s · cm),and the differences were statistically significant (Z =-2.62 and-2.20,P =0.01 and 0.03).The upper esophageal sphincter pressure (UESP) of the unclassified group was lower than that of the healthy control group (57.0 mmHg (31.3,77.8) mmHg vs.70.4 mmHg (49.4,97.8) mmHg),and the difference was statistically significant (Z =-2.64,P =0.02).There was significant difference in esophagogastric junction (EGJ) subtypes between the NERD group,the RH group,the FH group and the unclassified group (x2 =10.85,P =0.02);the proportion of type Ⅲ patients was highest in unclassified group,followed by NERD group,which were both higher than those of RH group and FH group.There was no significant difference in the proportion of esophageal motility subtypes between NERD group,RH group,FH group and unclassified group (P ＞ 0.05).Conclusions Patients with different phenotypes of heartburn and negative endoscopy finding should be classified by efficient diagnostic procedure according to the Rome Ⅳ criteria combined with HRM,24-hour pH monitoring and PPI test.The unclassified patients need further evaluation,especially for those with effective PPI test and negative pH monitoring.However,the evaluation of anti-reflux barrier function by the HRM parameters in patients with heartburn and negative endoscopic findings has certain limitations.

Eficacia diagnóstica de la impedancia basal nocturna media, un nuevo parámetro para el estudio de la enfermedad por reflujo gastroesofágico / Diagnostic efficacy of mean nocturnal basal impedance, a new parameter for the study of gastroesophageal reflux disease

Resumen Introducción y objetivos: el análisis de la impedancia basal nocturna media (IBNM) se ha propuesto para incrementar la precisión diagnóstica de enfermedad por reflujo erosiva (ERGE). Nuestro objetivo fue evaluar el rendimiento diagnóstico de esta prueba en un grupo de pacientes con ERGE conocida. Materiales y métodos: incluimos 123 individuos (58 con ERGE y 65 controles sanos) a quienes se les realizó pH-impedanciometría (pH-IMM) consecutiva entre enero de 2015 y junio de 2017. Todos los pacientes tenían endoscopia tomada en los 6 meses previos. El tiempo de exposición ácida (TEA) anormal (>4,2%) y la presencia de pirosis y/o regurgitación en los 6 meses previos fueron los criterios para el diagnóstico de ERGE. Se encontraron 58 pacientes con ERGE, 24 con enfermedad por reflujo erosiva (ERE) y 34 con enfermedad por reflujo no erosiva (ERNE). Los 65 restantes fueron controles sanos (CS) asintomáticos con EGD y pH-IMM normales. Todos los trazos de pH-IMM se reanalizaron para medir la IBNM por un segundo observador que desconocía los datos previos. El análisis estadístico incluyó pruebas múltiples de Bonferroni para comparar los grupos; regresión lineal para variables continuas; y análisis de curva ROC para buscar valor IBNM con mayor rendimiento. Para los diferentes parámetros de precisión diagnóstica se utilizó el punto de corte de la IBNM. Se usó significancia estadística con valor de p <0,01 e intervalos de confianza de 95% (IC 95%) para todos los cálculos. Resultados: los pacientes con ERE y ERNE presentaron valores de IBNM significativamente más bajos que el grupo control (p <0,01). Se observó una correlación negativa entre los valores de la IBNM y TEA (r = 0,59; p = <0,001), y también entre la IBNM y número de eventos de reflujo (r = 0,37; p = <0,001). En el análisis de curva ROC, el área bajo la curva de la IBNM fue de 0,941 (IC 95%: 0,894-0,987) y el punto de corte con mayor eficiencia 1102 ohms (sensibilidad 98,5%; especificidad 84,5%). Usando este valor (<1,102), la IBNM tuvo una sensibilidad para detectar ERGE de 91% (ERNE 86% y ERE 100%) y una especificidad de 98%. Conclusión: la IBNM tiene alta sensibilidad y especificidad para el diagnóstico de la ERGE. Adicionar esta prueba al análisis convencional de la pH-impedancia y a los métodos actuales de estudio de la ERGE puede mejorar significativamente nuestra capacidad para diagnosticar la enfermedad.

Abstract Introduction and Objectives: Analysis of nocturnal basal impedance (IBNM) has been proposed as a way to increase accuracy of GERD diagnosis. Our objective was to evaluate the diagnostic performance of this test in a group of patients known to have GERD. Materials and methods: We included 123 individuals: 58 with GERD and 65 healthy controls. They underwent consecutive pH-impedance monitoring between January 2015 and June 2017. All had undergone endoscopy in the 6 months prior to testing. Criteria used for diagnosis of GERD were abnormal acid exposure time (AET > 4.2%), pyrosis and/or regurgitation in the previous 6 months. We found 58 patients with GERD of whom 24 had erosive reflux disease (ERE) and 34 had non-erosive reflux disease (NERD). The remaining 65 were asymptomatic healthy controls with normal endoscopic results and pH impedance monitoring. A second observer who did not know the previous data measurements analyzed all pH impedance monitoring traces for IBMN. Statistical analysis included multiple Bonferroni tests for comparison between groups, linear regression for continuous variables, and receiver operating characteristic (ROC) curve analysis to find high performance IBNM values. The IBNM cutoff point was used for diagnostic precision parameters. Statistical significance was set at p <0.01, and 95% confidence intervals were used for all calculations. Results: IBNM measures were significantly lower for patients with ERE and NERD than for the control group (p <0.01). A negative correlation was observed between IBNM and acid exposure time values ​​(r = 0.59, p = <0.001) and also between IBNM and number of reflux events (r = 0.37, p = <0.001). ROC curve analysis found that the area under the curve for IBNM was 0.941 (95% CI: 0.894-0.987), and the cutoff point with the highest efficiency was 1,102 ohms (sensitivity 98.5%, specificity 84.5%). Using this value (<1.102), the IBNM had a sensitivity for detecting GERD of 91% (NERD 86% and ERE 100%) and a specificity of 98%. Conclusion: IBNM has high sensitivity and specificity for diagnosis of GERD. Addition of this test to conventional pH-impedance analysis and current methods for studying GERD can significantly improve our ability to diagnose this disease.

Prospective Single Arm Study on the Effect of Ilaprazole in Patients with Heartburn but No Reflux Esophagitis

PURPOSE: Patients with gastroesophageal reflux disease without esophagitis show varying responses to proton pump inhibitors (PPIs). The aim of this study was to objectively evaluate the effect of a new PPI, ilaprazole, on patients with heartburn but without reflux esophagitis. MATERIALS AND METHODS: This prospective study was performed on 20 patients with heartburn but without reflux esophagitis. All patients underwent upper endoscopy and 24-hr combined multichannel intraluminal impedance and pH esophageal monitoring (MII-pH). They were then treated with ilaprazole (20 mg) once daily for 4 weeks. The GerdQ questionnaire, histologic findings, and inflammatory biomarkers were used for assessment before and after ilaprazole. RESULTS: Among the 20 patients, 13 (65%) showed GerdQ score ≥8. Based on MII-pH results, patients were classified as true nonerosive reflux disease (n=2), hypersensitive esophagus (n=10), and functional heartburn (n=8). After treatment, patients showed a statistically significant improvement in GerdQ score (p < 0.001). Among histopathologic findings, basal cell hyperplasia, papillary elongation, and infiltration of intraepithelial T lymphocytes improved significantly (p=0.008, p=0.021, and p=0.008; respectively). Expression of TNF-α, IL-8, TRPV1, and MCP-1 decreased marginally after treatment (p=0.049, p=0.046, p=0.045, and p=0.042; respectively). CONCLUSION: Daily ilaprazole (20 mg) is efficacious in improving symptom scores, histopathologic findings, and inflammatory biomarkers in patients with heartburn but no reflux esophagitis.

Prevalence of dyspeptic symptoms and heartburn of adults in Belo Horizonte, Brazil / Prevalência de sintomas dispépticos e de pirose em uma população de adultos em Belo Horizonte, Brasil

ABSTRACT BACKGROUND Medical literature has shown dyspepsia and heartburn-related symptoms occur among 15% to 40% of the population. These symptoms can occur at any age and are more prevalent in women. OBJECTIVE Investigate the prevalence of dyspeptic symptoms and heartburn among individuals over 18. METHODS Individuals over 18 were randomly selected in public venues in Belo Horizonte/MG to participate. A standardized questionnaire that included questions related to social-demographic characteristics, eating habits, digestive symptoms, medical appointments, medications, exams, previous surgeries and comorbidities was applied. A questionnaire about functional dyspepsia diagnosis (Rome III) was also applied. RESULTS A total of 548 individuals were interviewed. Among these, 58.4% were women, 59.3% were white, 55.9% were single and the average age was 36 years. Within this group, 376 individuals (68.6%) declared to have some symptom and/or use medication to relieve dyspepsia symptoms, and for these patients were applied the Rome III questionnaire. Based on the diagnostic criteria for the questionnaire proposed by the Rome III consensus, the symptom of postprandial fullness was reported by 6.7% of the individuals, early satiety (3.5%) and epigastric pain (10.6%). The overlap of these symptoms was very frequent. The prevalence of functional dyspepsia was 10.6% (postprandial discomfort syndrome (8.2%) and epigastric pain syndrome (2.4%). Among all participants, 52.5% reported heartburn, and 11.1% presented this symptom at least once a week. The most used drug was omeprazole. CONCLUSION The prevalence of dyspeptic symptoms and heartburn among a Brazilian adult urban population is similar to those described in other countries.

RESUMO CONTEXTO Tem sido relatado que cerca de 15% a 40% da população geral apresenta alguma queixa dispéptica e/ou pirose. Os sintomas dispépticos podem surgir em qualquer idade e são mais prevalentes no sexo feminino. OBJETIVO Investigar a prevalência de sintomas dispépticos e pirose em indivíduos com idade superior a 18 anos. MÉTODOS Foram selecionados aleatoriamente indivíduos com idade superior a 18 anos, entrevistados em praças públicas de Belo Horizonte/MG, por meio de um questionário que abordou características sócio-demográficas, questões relacionadas aos hábitos alimentares, sintomas digestivos, consultas médicas, medicamentos, exames, antecedentes cirúrgicos, comorbidades e questionário específico para diagnóstico de dispepsia funcional (Roma III). RESULTADOS Foram entrevistados 548 participantes. Destes, 58,4% eram mulheres, 59,3% da raça branca, 56% solteiros e a idade média foi de 36 anos. Neste grupo, 376 indivíduos (68,6%) declararam ter algum sintoma e/ou utilizar algum medicamento para aliviar sintomas dispépticos. Para esses indivíduos, foi utilizado o questionário Roma III para o diagnóstico de dispepsia sendo sintoma de plenitude pós-prandial (6,7%), saciedade precoce (3,5%) e a dor ou queimação no estômago (azia) presente em 10,6%. A sobreposição desses sintomas foi muito frequente. A prevalência de dispepsia funcional foi de 10,6% (síndrome de desconforto pós-prandial (8,2%), síndrome da dor epigástrica (2,4%)). Dentre os participantes, 52,5% relatavam pirose, sendo que desses 11,1% apresentavam este sintoma, no mínimo, uma vez por semana. O medicamento mais utilizado foi o Omeprazol. CONCLUSÃO A prevalência dos sintomas dispépticos e pirose na população urbana adulta brasileira é semelhante a descrita em outros países.

The Application of the Rome IV Criteria to Functional Esophagogastroduodenal Disorders in Asia

The Rome criteria were amended as Rome IV. For functional esophageal disorders, the exclusion criteria have been more specifically revised based on further understanding of other esophageal disorders, including eosinophilic esophagitis and spastic and hypercontractile motor disorders. Another revised point is the more restrictive definition of gastroesophageal reflux disease, indicating that sensitivity to a physiological reflux burden may be placed more firmly within the functional group. For functional dyspepsia (FD), only minor changes were introduced, mainly to improve specificity. Among the major symptoms of FD, not only postprandial fullness, but also epigastric pain, epigastric burning, and early satiation should be “bothersome.” Investigation on the effect of meal ingestion on symptom generation has indicated that not only postprandial fullness and early satiety, but also epigastric pain, epigastric burning sensation and nausea (not vomiting) may increase after meals. Helicobacter pylori infection is considered a possible cause of dyspepsia if successful eradication leads to sustained resolution of symptoms for more than 6 months, and such status can be termed as “H. pylori–associated dyspepsia.” Prompt esophagogastroduodenoscopy and H. pylori testing and treatment would be more beneficial, especially in Asia, which has a high prevalence of gastric cancer. Acotiamide, tandospirone, and rikkunshito are the newly listed as treatment options for FD. For further therapeutic development, clinical studies based on the strict Rome IV criteria should be performed.

Esophageal Acidification During Nocturnal Acid-breakthrough with Ilaprazole Versus Omeprazole in Gastroesophageal Reflux Disease

BACKGROUND/AIMS: Though nocturnal acid-breakthrough (NAB) is common in gastroesophageal reflux disease (GERD) patients, its clinical importance results from esophageal acidification, which has been shown to be uncommon. Ilaprazole, a long-acting proton pump inhibitor, may cause NAB infrequently. Accordingly, we studied prospectively, (1) frequency and degree of esophageal acidification during NAB, and (2) frequency and severity of NAB while on ilaprazole versus omeprazole. METHODS: Fifty-eight consecutive patients with GERD on once daily ilaprazole, 10 mg (n = 28) or omeprazole, 20 mg (n = 30) for > one month underwent 24-hour impedance-pH monitoring prospectively. NAB was defined as intra-gastric pH one hour during night, and esophageal acidification as pH < 4 for any duration. Nocturnal symptoms (heartburn, regurgitation, and chest pain) were also recorded. RESULTS: Of the 58 patients (age 35.5 [inter-quartile range 26.5–46.0] years, 38 [65.5%], 42 (72.4%) had NAB. Though patients with NAB had lower nocturnal intra-gastric pH than without (2.8 [1.9–4.1] vs 5.7 [4.6–6.8], P < 0.001), frequency and duration of nocturnal esophageal acidification (17/42 vs 4/16, P = 0.360 and 0.0 [0.0–1.0] vs 0.0 [0.0–0.3] minutes, P = 0.260, respectively) and symptoms were comparable (13/42 vs 6/16, P = 0.750). Though ilaprazole was associated with less NABs (1 [range 1–2, n = 19] vs 1 [range 1–3, n = 23], P = 0.010) than omeprazole, the frequency, duration, and mean intra-gastric pH during NAB were comparable (19/28 vs 23/30, P = 0.560; 117 [0–315] vs 159 [69–287] minutes, P = 0.500; 1.02 [0.7–1.4] vs 1.04 [0.44–1.3], P = 0.620, respectively). CONCLUSIONS: Though NAB was common while patients were on a proton pump inhibitor, esophageal acidification was uncommon. Frequency and severity of NAB were comparable among patients on ilaprazole and omeprazole, except for the lesser number of NABs with ilaprazole.

The Relationship of the Post-reflux Swallow-induced Peristaltic Wave Index and Esophageal Baseline Impedance with Gastroesophageal Reflux Disease Symptoms

BACKGROUND/AIMS: The post-reflux swallow-induced peristaltic wave (PSPW) index and esophageal baseline impedance (BI) are novel impedance parameters used to evaluate esophageal chemical clearance and mucosal integrity. However, their relationship with reflux symptoms is not known. We aim to evaluate the correlations of PSPW index and esophageal BI with gastroesophageal reflux disease (GERD) symptoms. METHODS: We performed a retrospective review of multichannel intraluminal impedance and pH (MII-pH) tracings in patients with suspected GERD. Reflux symptoms were also analyzed from checklists using ordinal scales. The PSPW index and esophageal BIs in 6 spots (z1–z6) were measured. Bivariate (Spearman) correlation was used to analyze the relationship between the PSPW index or esophageal BI, and the degree of GERD symptoms measured. RESULTS: The MII-pH records of 143 patients were analyzed. The PSPW index was significantly lower in patients who had heartburn and negatively correlated with the degree of heartburn (r = −0.186, P < 0.05). On the contrary, the PSPW index was not significantly correlated with the degree of dysphagia (r = −0.013, P = 0.874). Distal esophageal BI was not significantly correlated with heartburn, but negatively correlated with the degree of dysphagia (z3: r = −0.328, z4: r = −0.361, z5: r = −0.316, z6: r = −0.273; P < 0.05). CONCLUSIONS: These findings suggest that delayed chemical clearance of the esophagus may induce heartburn, but that it is not related to dysphagia. However, a lack of esophageal mucosal integrity may be related to dysphagia.