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Reflux hypersensitivity (RH) is one of the phenotypes of gastroesophageal reflux disease. The latest Rome IV defines RH as a condition with typical reflux symptoms and positive reflux-symptom association despite normal acid exposure. Subsequently, the Lyon consensus proposed detailed cutoff values for the criteria on the basis of experts’ consensus. Rome IV brought a clear-cut perspective into the pathophysiology of gastroesophageal reflux disease and the importance of esophageal hypersensitivity. This perspective can be supported by the fact that other functional gastrointestinal disorders such as irritable bowel syndrome and functional dyspepsia often overlap with RH. Although several possible pathophysiological mechanisms of esophageal hypersensitivity have been identified, there is still unmet medical needs in terms of treatment for this condition. This review summarizes the current knowledge regarding RH.

IntroductionHeartburn 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.MethodsThirty-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.ResultsTranscriptomic analysis detected higher mast cell abundance in BO, ERD, and NERD compared to healthy controls (p

La fisiopatología de la enfermedad por reflujo gastroesofágico (ERGE) es compleja y multifactorial, involucrando factores como la motilidad gástrica, la composición del contenido estomacal, la barrera antirreflujo, el aclaramiento esofágico y la salud de la mucosa esofágica. La integridad de la mucosa es esencial para determinar la gravedad del daño y la percepción de los síntomas. La naturaleza del material refluido, su composición y cantidad, influyen en el daño y los síntomas. Mecanismos de defensa, como la peristalsis esofágica y la saliva, influyen en cuánto tiempo el contenido refluido está en contacto con la mucosa esofágica. La intensidad de los síntomas varía entre individuos debido a factores neurológicos, psicológicos y periféricos, como la hipervigilancia. Comprender estos mecanismos es crucial para ofrecer tratamientos personalizados basados en la causa predominante de la ERGE.

La Clasificación de Chicago v4.0 (CCv4.0) es el esquema actualizado para clasificar las alteraciones de la motilidad esofágica utilizando la métrica de la manometría de alta resolución (HRM). Para desarrollar la CCv4.0, 52 expertos internacionales diversos separados en siete subgrupos de trabajo utilizaron una metodología formalmente validada, en un periodo de dos años. Las actualizaciones claves de la CCv4.0 consisten en un protocolo de HRM más riguroso y expansivo que incorpora las posiciones en decúbito supino y sedestación, así como pruebas provocadoras; una definición refinada de la obstrucción del flujo de salida de la unión esofagogástrica (EGJOO), criterios diagnósticos más estrictos para la motilidad esofágica inefectiva, y descripción de la métrica basal de la EGJ. Adicionalmente, la CCv4.0 se propuso definir el diagnóstico de alteración de la motilidad como conclusivo o no conclusivo con base en los síntomas asociados, los hallazgos en las pruebas provocadoras, y los resultados de los exámenes de apoyo como el esofagograma con tableta de bario y/o la prueba con sonda para imagen endoluminal funcional. Estos cambios buscan minimizar la ambigüedad presente en iteraciones previas de la Clasificación de Chicago; además proveen criterios más estandarizados y rigurosos para los patrones de alteración de la peristalsis y obstrucción de la EGJ.

RACIONAL: Por padronização aceita internacionalmente, posiciona-se o sensor distal de pHmetria esofágica a 5 cm acima da borda superior do esfíncter inferior do esôfago, localizado por manometria esofágica. Porém, vários autores sugerem técnicas alternativas de posicionamento que prescindem da manometria. Dentre essas, destaca-se a da viragem do pH, tema este controverso pela sua duvidosa confiabilidade. OBJETIVO: Avaliar a adequação do posicionamento do sensor distal de pHmetria pela técnica de viragem do pH, considerando-se a presença, o tipo e o grau de erro de posicionamento que tal técnica proporciona, e também estudar a influência da posição adotada pelo paciente durante a técnica da viragem. MÉTODOS: Foram estudados de modo prospectivo, durante o período de 1 ano, 1.031 pacientes. Durante entrevista clínica, foram registrados os dados demográficos e as queixas clínicas apresentadas. Todos foram submetidos a manometria esofágica para localização do esfíncter inferior do esôfago e a técnica da viragem do pH. A identificação do ponto de viragem foi realizada de dois modos distintos, caracterizando dois grupos de estudo: com o paciente sentado (grupo I - 450 pacientes) e com o paciente em decúbito dorsal horizontal (grupo II - 581 pacientes). Após a identificação do ponto de viragem, o sensor distal de pHmetria era posicionado na posição padronizada, baseada na localização manométrica do esfíncter. Registrava-se onde seria posicionado o sensor de pH se fosse adotada a técnica da viragem. Para avaliação da adequação do posicionamento, considerou-se que o erro é representado pela diferença (em centímetros) entre a localização padronizada (manométrica) e a localização que seria adotada caso fosse empregada a técnica da viragem. Considerou-se que o erro seria grosseiro se fosse maior que 2 cm. Analisou-se também o tipo de erro mais freqüente (se acima ou abaixo da posição padronizada). Foram incluídos todos pacientes que aceitaram participar da pesquisa e excluídos os casos nos quais não se identificou acidificação intragástrica. RESULTADOS: Se fosse adotada a técnica da viragem, haveria erro no posicionamento do sensor em 945 pacientes (91,6%), portanto, o sensor seria posicionado na posição padronizada em apenas 86 (8,4%) casos. Em relação à caracterização do grau de erro, haveria erro considerado grosseiro em 597 (63,2%) pacientes. Em relação ao tipo de erro, o sensor seria posicionado abaixo do local padronizado em 857 (90,7%) casos. Não houve diferença significante entre os dois grupos de estudo em relação a nenhum dos parâmetros analisados, indicando que a posição adotada pelo paciente durante a manobra da viragem não interfere no erro inerente à técnica. CONCLUSÕES: 1. O posicionamento do sensor distal de pHmetria pela técnica da viragem do pH não é confiável. 2. A técnica da viragem proporciona margem de erro expressiva. 3. O tipo de erro mais comum que tal modalidade técnica proporciona é o posicionamento mais distal do sensor, que pode superestimar a ocorrência de refluxo. 4. Não há influência da posição adotada pelo paciente durante a realização da técnica da viragem do pH na eficiência do método.BACKGROUND: By internationally accepted standardization, the esophageal pH-meter distal sensor is positioned 5 cm above the superior border of the lower esophageal sphincter, identified by esophageal manometry. However, several authors suggest alternative positioning techniques that leave out the manometry; among such techniques, the pH step-up is the one to be pointed out. This subject is controversial; some publications state that the step-up technique is not reliable while some others consider it reliable. AIMS: Considering the existent controversy and the small number of prospective works with suitable sample and methodology, we have idealized the present study, that aims the evaluation of the suitability of the pH-meter distal sensor positioning based on the step-up technique, by analyzing the presence, the type and the degree of the error of positioning that such technique provides and the influence of the position adopted by the patient during the procedure. METHODS: One thousand and thirty one patients conducted to the esophageal pH-meter procedure were studied in a prospective way. During the clinical interview, the demographic data and the presented clinical complaints were registered. All the patients were submitted to both esophageal manometry in order to localize the lower esophageal sphincter and the pH step-up technique, that consists of the introduction of the pH-meter sensor in the gastric chamber and in the sensor's gradual traction until the pH steps up to levels over 4. The step-up point was identified by two distinct ways, characterizing two study groups: with the sitting patient (group I - 450 patients) and with the patient in supine position (group II - 581 patients). After the step-up point identification, the pH-meter distal sensor was placed in the standard position (based on the sphincter manometric placement). It was registered where the pH sensor would be positioned if the step-up technique were adopted. To evaluate the positioning suitability, the error was considered to be represented by the difference (in centimeters) between the suitable placement (manometry) and the one that would be adopted in case the step-up technique were adopted. The positioning error was considered rough if it were larger than 2 cm. The most frequent type of error was also analyzed (if above or below the standard position). RESULTS: It was observed that if the step-up technique were adopted, there would be error in the sensor positioning in 945 patients (91.6%). In terms of error degree, there would be a rough error in 597 (63.2%) cases. Concerning the type of error, the sensor would be positioned below the standard place in 857 (90.7%) patients. As to the interference of the position adopted by the patient during the step-up technique, it was observed that there was no significant difference among the groups of study in any of the analyzed parameters. CONCLUSIONS: 1. The positioning of the pH-meter distal sensor by the step-up technique is not reliable; 2. the step-up technique provides expressive error margin; 3. the most common type of error that such technique mode provides is the placement of the sensor below the standard positioning, which may overestimate the reflux occurrence; 4. there is no influence in the position adopted by the patient during the pH step-up technique procedure, in terms of method efficiency.

Abstract  Current management algorithms propose pH monitoring under proton pump inhibitors (PPIs) in suspected gastroesophageal reflux disease (GERD) with insufficient treatment response, but recent observations challenge this approach because of its low yield. Aim To perform an audit of the outcomes of pH monitoring under PPI therapy in our unit, and to study the yield of additional nonacid reflux monitoring. Methods All pH monitoring studies under antireflux therapy since 1997, with or without simultaneous Bilitec® monitoring, were analyzed. Results From 1997 to 2003, 347 patients (157 men, mean age 49.4 ± 0.8 years) underwent pH studies on PPI therapy (28% half-, 67% full-, and 5% double-dose PPI) for persisting typical (53%) or atypical (75%) symptoms. In 184 patients, simultaneous Bilitec® monitoring was performed. Esophageal pH monitoring on PPI was pathological in 105 (30%) patients. Pathological pH monitoring on PPI was associated with typical reflux symptoms (64 versus 52%, P = 0.03), and a higher prevalence of persisting esophagitis (54 versus 36%, P  P ® increased the rate of abnormal results over pH monitoring alone, from 38% to 69% on half-dose, from 27% to 69% on full-dose, and from 0% to 38% on double-dose PPI. Conclusions The rate of abnormal pH monitoring in symptomatic GERD patients while on PPI therapy is relatively low, especially in those on double-dose PPI. Combined pH and Bilitec® monitoring significantly increased the rate of ongoing pathological reflux compared to pH alone in refractory to PPI therapy GERD patients. [ABSTRACT FROM AUTHOR]

Abstract   Background Non-erosive reflux disease (NERD) and erosive esophagitis (EE) are the most common phenotypic presentations of gastroesophageal reflux disease (GERD). Aim To assess acid and non-acid reflux patterns in patients with EE and NERD using combined esophageal pH-impedance monitoring. Methods A total of 26 GERD patients off acid-suppressive medication and ten healthy volunteers (HV) underwent upper endoscopy and 24-h pH-impedance monitoring. Analysis of the pH-impedance signals included total reflux time, number of reflux episodes according to gas–liquid composition, and pH (acid, non-acid). Results EE was identified in 13 patients and NERD in 13 patients. Pathologic acid reflux was found in 92.3 and 69.2% of patients with EE and NERD, respectively (P = 0.15). When compared to HV, EE patients and NERD patients showed a higher incidence of acid (P = 0.002 and P P = 0.03 and P = 0.001, EE vs. HV and NERD vs. HV, respectively). Mean reflux times, as assessed by both pH-metry and impedance monitoring, and incidence of acid and non-acid reflux episodes were similar in EE and NERD patients. In the supine position, however, EE patients showed a higher incidence of acid (P = 0.048) and liquid reflux episodes (P = 0.07). Conclusion Whereas EE patients have more acid reflux episodes in the supine position than NERD patients, patients with EE and NERD have similar non-acid reflux patterns. This observation lends support to the notion that non-acid reflux is less damaging to the esophageal mucosa than acid reflux. [ABSTRACT FROM AUTHOR]