Esophageal Hypersensitivity Research Articles

Wake up to gastro-oesophageal reflux disease: The interplay between arousal and night-time reflux.

This review examines the temporal association between nocturnal gastro-oesophageal reflux and sleep-arousal cycles. Most nocturnal gastro-oesophageal reflux events occur during the awake cycle, and arousals precede most nocturnal gastro-oesophageal reflux events, indicating that arousal from sleep predisposes to nocturnal gastro-oesophageal reflux. This sheds light on the complex relationship between nocturnal gastro-oesophageal reflux and sleep, and has implications for managing nocturnal gastro-oesophageal reflux symptoms. The appearance of symptoms and the pathophysiology of nocturnal gastro-oesophageal reflux are influenced by sleep hygiene, sleep disturbances and the misalignment of circadian rhythms. Nocturnal gastro-oesophageal reflux and its related sleep disorders are prevalent and negatively impact the quality of life. There is conflicting evidence on whether nocturnal gastro-oesophageal reflux and sleep disturbances are causally linked, and whether sleep disturbances drive nocturnal gastro-oesophageal reflux. Poor sleep quality increases oesophageal hypersensitivity and overall acid exposure. The nocturnal gastro-oesophageal reflux is linked to the more severe forms of gastro-oesophageal reflux disease, especially with atypical/extra-oesophageal manifestations and complications of mucosal damage such as oesophagitis and stricture, Barret's oesophagus, and oesophageal adenocarcinoma. This review highlights the role of sleep problems in presenting nocturnal gastro-oesophageal reflux, and the potential benefits of treating sleep disturbances in enhancing patient care and quality of life.

Refractory Gastroesophageal Reflux Disease: Diagnosis and Management.

Gastroesophageal reflux disease (GERD) is common, with increasing worldwide disease prevalence and high economic burden. A significant number of patients will remain symptomatic following an empiric proton pump inhibitor (PPI) trial. Persistent symptoms despite PPI therapy are often mislabeled as refractory GERD. For patients with no prior GERD evidence (unproven GERD), testing is performed off antisecretory therapy to identify objective evidence of pathologic reflux using criteria outlined by the Lyon consensus. In proven GERD, differentiation between refractory symptoms (persisting symptoms despite optimized antisecretory therapy) and refractory GERD (abnormal reflux metrics on ambulatory pH impedance monitoring and/or persistent erosive esophagitis on endoscopy while on optimized PPI therapy) can direct subsequent management. While refractory symptoms may arise from esophageal hypersensitivity or functional heartburn, proven refractory GERD requires personalization of the management approach, tapping from an array of non-pharmacologic, pharmacologic, endoscopic, and surgical interventions. Proper diagnosis and management of refractory GERD is critical to mitigate undesirable long-term complications such as strictures, Barrett's esophagus, and esophageal adenocarcinoma. This review outlines the diagnostic workup of patients presenting with refractory GERD symptoms, describes the distinction between unproven and proven GERD, and provides a comprehensive review of the current treatment strategies available for the management of refractory GERD.

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.

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.

Lemborexant Attenuates Regurgitation without Worsening Objective Parameters on Reflux Monitoring in Patients with Gastroesophageal Reflux Disease and Insomnia: A Single-Arm Proof-of-Concept Study

Introduction: Esophageal hypersensitivity is associated with gastroesophageal reflux disease (GERD). Since sleep disturbance causes esophageal hypersensitivity, hypnotics may ameliorate GERD. However, zolpidem prolongs esophageal acid clearance. Lemborexant is a new hypnotic with higher efficacy and fewer adverse events than zolpidem. Therefore, the present study investigated the effects of lemborexant on GERD. Methods: Patients with heartburn and/or regurgitation and insomnia who did not take acid suppressants or hypnotics in the last month were recruited. Symptom assessments using GerdQ and reflux monitoring were performed before and after a 28-day treatment with 5 mg lemborexant at bedtime. The primary outcome was a change in the total GerdQ score, excluding the score for insomnia. Secondary outcomes were changes in each GerdQ score and the following parameters on reflux monitoring: the acid exposure time (AET), number of reflux events (RE), acid clearance time (ACT), and post-reflux swallow-induced peristaltic wave (PSPW) index. Results: Sixteen patients (age 45.0 [33.3–56.0], 11 females [68.8%]) completed the intervention (1 patient did not tolerate the second reflux monitoring). The total GerdQ score, excluding the score for insomnia, did not significantly change (8.0 [6.0–9.0] before vs. 7.0 [6.3–9.0] after p = 0.16). GerdQ showed the significant attenuation of regurgitation (2.0 [2.0–3.0] vs. 1.0 [0–2.8] p = 0.0054) but not heartburn (2.5 [1.0–3.0] vs. 1.0 [0.3–2.0] p = 0.175). No significant differences were observed in AET, RE, ACT, or PSPW index before and after the intervention. Conclusion: Lemborexant attenuated regurgitation without the worsening of objective reflux parameters. A randomized placebo-controlled study is warranted in the future.

Esophageal Reflux Hypersensitivity: A Comprehensive Review.

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.

S1116 Transoral Incisionless Fundoplication Is a Safe and Effective Therapeutic Option for Refractory GERD: A 3-Year Retrospective Experience at a Quaternary Center

Introduction: Refractory GERD is seen in up to 40% of patients who experience persistent symptoms despite optimal therapy with acid-suppressing agents, including proton pump inhibitors (PPI) and H2 blockers (H2B). Such individuals may be candidates for invasive interventions. Transoral incisionless fundoplication (TIF) is a minimally invasive intervention, which can be performed alone or in conjunction with laparoscopic hiatal hernia repair (HHR). Our study aimed to evaluate the technical and clinical success of TIF performed at a quaternary center in the management of refractory GERD. Methods: This is an IRB approved retrospective chart review of patients who underwent TIF alone or TIF with HHR (TIF+HHR) for refractory GERD from 2018 to 2021. Technical success was defined as completed procedures without major complications. Clinical success was measured by reduction in PPI and/or H2B use as well as symptom resolution quantified by the GERD HQRL Questionnaire. Results: A total of 58 patients with a mean age of 55.7 years were included of whom 62.7% were female. 19.0% underwent TIF only, while 81.0% underwent TIF+HHR. Hill grade I, II, III, and IV was respectively present in 9.3%, 32.6%, 44.2%, and 9.3% of patients with a mean hiatal hernia length of 2.36 cm. The technical success rate was 98.3% - there was only one patient in whom the procedure could not be completed as the TIF device was not able to be inserted even after esophageal dilation. At 12 months, 85.7% of patients reported reduction in PPI use of whom 76.2% stopped completely and 9.6% reduced dosing by ≥ 50%. Similar results were seen in those with H2B use with 85.7% of patients stopping completely. Preop mean HQRL score was 29.59 which decreased significantly to 6.56 and 3.27 at 6 and 12 months, respectively. At 12 months, 81.8% reported satisfaction with their condition, whereas 9.1% were neutral and 9.1% were dissatisfied. Complications occurred in 4 patients, including self-resolving oozing and superficial mucosal tears not requiring intervention. Conclusion: Our study confirms that TIF is a viable treatment option in the management of refractory GERD. Similar to prior studies, we experienced high technical success rates with no major complications as well as clinical success with a majority of patients being able to reduce or stop PPI and/or H2B completely. In those who were unable to be titrated off acid suppression, postop evaluation suggested alternative diagnoses such as esophageal hypersensitivity or functional dyspepsia.

Knowledge gaps in the management of refractory reflux-like symptoms: Healthcare provider survey.

Refractory reflux-like symptoms have a substantial impact on patients and healthcare providers. The aim of the survey was to qualitatively assess the needs and attitudes of practicing clinicians around the management of refractory reflux symptoms and refractory gastroesophageal reflux disease (rGERD). An International Working Group for the Classification of Oesophagitis (IWGCO) steering committee invited clinicians to complete an online survey including 17 questions. Of the 113 clinicians who completed the survey, 70% were GIs, 20% were primary care physicians, and 10% were other specialties. Functional heartburn was considered the most common reason for an incomplete response to proton pump inhibitor (PPI) therapy (82%), followed by stress/anxiety (69%). More GIs identified esophageal hypersensitivity as a cause, while more non-GIs identified esophageal dysmotility and non-reflux-related esophageal conditions. As the first step, most clinicians would order investigations (70-88%). Overall, 72% would add supplemental therapy for patients with partial response, but only 58% for those with non-response. Antacid/alginate was the most common choice overall, while non-GIs were more likely to add a prokinetic than were GIs (47.8 vs. 24.1%). Approximately 40% of clinicians would switch PPIs in patients with partial response, but only 29% would do so in non-responders. Preferences for long-term therapy were highly variable. The most common initial investigation was upper endoscopy. Choice of esophageal manometry and pH monitoring was more variable, with no clear preference for whether pH monitoring should be conducted on, or off, PPI therapy. The survey identified a number of challenges for clinicians, especially non-GI physicians, treating patients with refractory reflux-like symptoms or rGERD on a daily basis.

The Clinical value of brain-gut behavioral therapies for functional esophageal disorders and symptoms.

Functional esophageal disorders (functional chest pain, functional heartburn, reflux hypersensitivity, globus, and functional dysphagia) are the disorders of gut-brain interactions (DGBI) and present with esophageal symptoms not associated with a structural, major motility or underlying inflammatory condition. Notably, many patients with the latter conditions may still experience esophageal symptoms beyond what could be attributed to their underlying disorders. Esophageal visceral hypersensitivity and hypervigilance are the two pathways which drive functional esophageal disorders and symptoms. These functional esophageal symptoms may be severe, leaving patients with impaired quality of life and inadequate treatment outcomes. Neuromodulators are the foundation of the pharmacologic approach of many of the functional esophageal disorders and symptoms, modulating both peripheral and central hyperalgesia. There is also emerging evidence for brain-gut behavioral therapies (BGBT) such as gut-directed hypnotherapy and cognitive behavior therapy for the treatment of a variety of DGBIs. In this issue of Neurogastroenterology and Motility,Hurtte et al. add to the literature on the effectiveness of BGBT in treating functional esophageal symptoms, showing multimodal therapy with pharmacologic and non-pharmacologic approaches led to improvement in health-related quality of life. In this review, we outline the mechanistic underpinnings of BGBT and review the existing evidence for BGBT for functional esophageal disorders and symptoms. We also highlight the future research directions and challenges for scaling these therapies.

Tracheobronchial-esophageal reflex initiates esophageal hypersensitivity and aggravates cough hyperreactivity in guinea pigs with esophageal acid infusion

Esophageal-tracheobronchial reflex is considered the main mechanism underlying cough due to gastroesophageal reflux, and is associated with esophageal hypersensitivity. We hypothesized that tracheobronchial-esophageal reflex may also exist, and may be related to esophageal hypersensitivity. To test this hypothesis, conscious and ether-anesthetized guinea pigs were subjected to repetitive capsaicin inhalation to establish models of cough (conscious) and cough-free (anesthetized) airway injury, respectively, followed by esophageal acid infusion. Recurrent capsaicin inhalation induced similar cough hyperreactivity to inhaled capsaicin after esophageal acid infusion in guinea pigs with cough and guinea pigs with cough-free airway injury during recurrent capsaicin inhalation. Cough hyperreactivity, along with overexpression of transient receptor potential vanilloid 1 (TRPV1) receptors in esophageal mucosa and in nerve fibers of tracheal mucosa of guinea pigs were blocked by pretreatment with esophageal infusion of capsazepine, but not atropine. Thus, recurrent airway nociceptive stimuli induce esophageal hyperreactivity via a tracheobronchial-esophageal reflex mediated by vagal C afferents expressing TRPV1, and enhance cough due to reflux.

Finding relief for the self-conscious esophagus: laparoscopic anti-reflux surgery and the esophageal hypersensitivity and anxiety scale.

Measures of mood and effective coping strategies have notable correlations with quality of life and treatment responses. There is evidence that patients with previously diagnosed anxiety disorders have less improvement in patient-reported outcome measures (PROMs) after laparoscopic anti-reflux surgery (LARS) and that objective pathology does not correlate well with symptom severity. We were interested in investigating whether anxiety and hypervigilance, as measured preoperatively with the esophageal hypervigilance anxiety scale (EHAS), is associated with the improvement in GERD-specific PROMs and EHAS scores 6months after LARS. We performed a retrospective cohort study of 102 adult patients (31% men, average age 64) who underwent LARS. In the preoperative evaluation, baseline gastroesophageal reflux disease-health-related quality of life (GERD-HRQL), laryngopharyngeal reflux symptom index (LPR-RSI) and EHAS scores were collected in addition to the standard reflux workup, including endoscopy, manometry, barium swallow, and pH study. For all three surveys, a higher score represents worse symptom severity. At 6months postoperatively, 70 patients completed repeat GERD-HRQL, LPR-RSI, and EHAS surveys. We then analyzed for surgical and patient-related factors associated with improvement in the 6-month postoperative GERD-HRQL and LPR-RSI scores. There was a statistically significant decrease in the GERD-HRQL (25 vs. 2, p < 0.001), LPR-RSI (17 vs. 3, p < 0.001) and EHAS (34 vs. 15, p < 0.001) 6months after LARS. On multivariable linear regression, a higher baseline EHAS score was independently associated with a greater improvement in GERD-HRQL (β 0.35, p < 0.001) and LPR-RSI (β 0.19, p = 0.03) 6-months after LARS. Additionally, the degree of improvement in EHAS, GERD-HRQL, and LPR-RSI was not influenced by the type of LARS performed or by the severity of disease. These findings are consistent with literature suggesting that measures of psychoemotional health correlate better with symptom intensity than objective pathology. We found that patients with a higher EHAS score have greater symptom severity and lower quality of life at baseline. Novel findings to this study are that patients with a higher preoperative EHAS, a measure of psychoemotional health, actually benefitted more from surgery and not less, which has been the traditional view in the literature. Future studies are warranted to establish directionality and explore the role of preoperative cognitive behavioral therapy with LARS for patients with significant symptoms of hypervigilance and anxiety.

Современные аспекты диагностики и лечения рефрактерной гастроэзофагеальной рефлюксной болезни

Objective of the Review: To analyze current data on the diagnosis and treatment of refractory gastroesophageal reflux disease (GERD). Key points. Refractory GERD is diagnosed when there is insufficient response to proton pump inhibitors (PPIs) twice daily for 8 weeks with the presence of pathological gastroesophageal reflux. Possible mechanisms underlying PPI-refractory symptoms characteristic of GERD include persistence of pathological reflux, esophageal hypersensitivity to reflux, association of symptoms with other diseases, and functional nature of symptoms. To diagnose refractory GERD, a thorough analysis of symptoms, esophagogastroscopy with morphological examination, pH-impedancemetry and esophageal manometry are performed. Treatment includes dietary and lifestyle modifications to reduce body weight in obese patients, optimization of PPI prescribing, use of other drugs, and, if indicated, surgery. Conclusion. Diagnosing the reasons for the decrease in the effectiveness of PPIs in patients with GERD is a complex process that requires the use of modern endoscopic methods with the performance of a morphological study of the esophagus, pH-impedance testing and highresolution manometry to determine the nature of reflux, the relationship of reflux with symptoms of GERD and the differential diagnosis of various GERD syndromes. The choice of therapy for patients with refractory GERD is determined by the results of the examination and the final diagnosis. Keywords: refractory gastroesophageal reflux disease, proton pump inhibitors, diagnosis, treatment.

Chronic pancreatitis in comorbidity with gastroesophageal reflux disease (features of the course of gastroesophageal reflux disease)

In this article, the authors emphasize the relevance of studying the features of the course of gastroesophageal reflux disease (GERD) both in children and adults, and in old age (including chronic pancreatitis). Attention is drawn to the different important mechanisms of GERD development in children and adults. As it is impossible to collect anamnesis in children before they start speaking, it is necessary to ask the parents about the so-called “red flags” (frequent fountain-like vomiting, the child is badly gaining weight, repeated pneumonia, diarrhea, refusal to drink or eat). One of the important features is a child’s crying during 1–2 hours.
 It is difficult to make a differential diagnosis in adults between GERD phenotypes, especially in comorbidity with chronic pancreatitis, which makes appropriate adjustments to the clinical picture (which the authors focus on). Differential diagnosis of non-erosive GERD, such GERD phenotypes as reflux esophageal hypersensitivity, functional heartburn, low and high grade reflux esophagitis, Barrett’s esophagus, regurgitation-dominant GERD, extraesophageal phenotype and reflux chest pain syndrome is carried out.
 The authors agree with those provisions that indicate that GERD is a family of different syndromes that differ in the mechanisms of development, clinical picture and make up certain phenotypes of the disease, which require a differentiated approach to treatment tactics and strategies, secondary prevention (including chronic pancreatitis).

Upregulation of acid sensing ion channels is associated with esophageal hypersensitivity in GERD

Proton pump inhibitors (PPIs) are the mainstay of therapy for gastroesophageal reflux disease (GERD) but up to 60% of patients have inadequate response to therapy. Acid sensing ion channels (ASICs) play important roles in nociception. This study aimed to investigate whether the increased expression of ASICs results in neuronal hyperexcitability in GERD. Esophageal biopsies were taken from GERD patients and healthy subjects to compare expression of ASIC1 and 3. Next, gene and protein expression of ASIC1 and 3 from esophageal mucosa and dorsal root ganglia (DRG) neurons were measured by qPCR, Western‐blot and immunofluorescence in rodent models of reflux esophagitis (RE), non‐erosive reflux disease (NERD), and sham operated groups. Excitability of DRG neurons in the GERD and sham groups were also tested by whole‐cell patch‐clamp recordings. We demonstrated that ASIC1 and 3 expression were significantly increased in patients with RE compared with healthy controls. This correlated positively with symptom severity of heartburn and regurgitation (p < .001). Next, ASIC1 and 3 gene and protein expression in rodent models of RE and NERD were similarly increased in esophageal mucosa as well as T3–T5 DRG neurons compared with sham operation. DRG neurons from RE animals showed hyperexcitability compared with sham group. However, intrathecal injection of ASIC specific inhibitors, PcTx1 and APTEx‐2, as well as silencing ASIC1 and 3 genes with specific siRNAs prevented visceral hypersensitivity. Overall, upregulation of ASIC1 and 3 may lead to visceral hypersensitivity in RE and NERD and may be a potential therapeutic target for PPI non‐responsive patients.

S2113 Eosinophilic Esophagitis in a Patient With Oral Allergy Syndrome: Is There an Overlap?

Introduction: Food allergies can trigger systemic manifestations outside of the GI tract, most notably anaphylaxis. Eosinophilic esophagitis (EoE) is a chronic, immune-mediated eosinophilic infiltration of the esophagus with a higher prevalence in patients with food allergy than the general population (1 in 20 vs 1 in 2500). Oral allergy syndrome (OAS) is a clinical diagnosis describing symptoms including swelling and itching of the oral mucosa and may serve as a surrogate to identify patients with EoE. Case Description/Methods: A 49-year-old female with a history of OAS, esophageal hypersensitivity and non-erosive acid reflux presented with nausea and abdominal discomfort. Endoscopic esophageal biopsies revealed eosinophilic infiltrate confirming EoE. Omeprazole therapy provided incomplete symptom control with persistent episodic retrosternal burning and globus sensation, which responded to carafate. Repeat endoscopy three years later, showed persistent esophageal mucosal changes consistent with EoE and erythematous mucosa in the gastric body and antrum. She continued to abstain from seafood but was reluctant to initiate elimination diets and will likely require localized steroid treatment. Discussion: Allergic disease of the GI tract can occur in an IgE-dependent (OAS), IgE-independent or mixed fashion (EoE). The culprit antigen in OAS is birch pollen Betv1, sharing up to 70% homology with amino acids in certain fruits. Food and airborne allergens play a pivotal role in EOE. OAS and EoE both have a strong association with atopic conditions. However, common food allergens tested in EoE are dairy and wheat which differ from OAS. In a study of 186 patients with EoE, approximately 50% of patients were found to have concomitant OAS. Sensitization to at least 1 pollen and 1 aeroallergen was noted in 82.4% and 90.4% respectively. The authors proposed the inciting factor in EoE may be sensitization to pollen allergens resulting in subsequent cross-reactivity with food proteins. A novel syndrome coined Food-Induced immediate Response of the Esophagus (FIRE) representing retrosternal pain with ingestion of certain foods has been associated with EoE with known overlap with OAS. The treatment for OAS is avoidance and heat-treatment whereas elimination diets and steroids form the mainstay of management for EoE. In summary, with increasing diagnosis of allergic GI tract disease, OAS may serve as a screening tool for EoE. Concomitant OAS may contribute to a more aggressive course of EoE as was seen in our patient.Figure 1.: esophageal web/stricture from initial EGD.

S398 Functional Heartburn and Esophageal Hypersensitivity Frequency in Patients With Refractory Gastroesophageal Reflux Symptoms: Using the Roma IV Consensus and a Series of Diagnostic Procedures in Lima, Peru

S398 Functional Heartburn and Esophageal Hypersensitivity Frequency in Patients With Refractory Gastroesophageal Reflux Symptoms: Using the Roma IV Consensus and a Series of Diagnostic Procedures in Lima, Peru

Post-per-oral endoscopic myotomy heartburn: It's not always reflux: Expert review.

Patients with achalasia frequently develop gastroesophageal reflux (GER)-related symptoms and complications after per-oral endoscopic myotomy (POEM). Reflux symptoms are thought to be due to GER and the current treatment of post-POEM GER focuses on acid suppression with proton pump inhibitors (PPI). However, reflux symptoms in achalasia patients post-POEM can be due to true reflux, nonreflux esophageal acidification due to stasis or acid fermentation, or esophageal hypersensitivity to chemical or mechanical stimuli. True acidic reflux is not always the cause of reflux symptoms. Twenty-four-hour pH monitoring with impedance is essential to differentiate causes of esophageal acidification. PPI is useful only in true acidic reflux. Detection of acid fermentation requires manual review of a 24-h pH study, as automated review often overestimates acid exposure time due to its inability to differentiate true reflux from fermentation. Stasis of ingested acidic food warrants evaluation of esophageal emptying by timed barium esophagogram. In cases of inadequate emptying, esophagogastric junction (EGJ) distensibility can be evaluated by a functional lumen imaging probe. Impaired distensibility with inadequate esophageal emptying suggests treatment failure and may require retreatment. In treatment-refractory patients, esophageal hypersensitivity should be considered and treated with neuromodulators. Thus, the diagnostic approach to post-POEM reflux symptoms should evolve to identify various patterns of esophageal acidification, esophageal emptying patterns, EGJ distensibility, and hypersensitivity. Consequently, the treatment of GER post-POEM should not be limited to treating esophageal acidification by reflux, but should encompass other causes of acidification and esophageal hypersensitivity.

Pepsin and pH of Gastric Juice in Patients With Gastrointestinal Reflux Disease and Subgroups.

The aim of this study was to investigate the pepsin values and pH results of gastric juice among the subtypes of gastroesophageal reflux disease (GERD) and functional heartburn. The major destructive agents of GERD on the esophageal epithelium are gastric acid and pepsin. No precise information about pepsin concentration in gastric juice exists. Ninety patients with GERD, 39 erosive reflux disease (ERD) Los Angeles (LA) grade A/B, 13 ERD LA grade C/D, 19 nonerosive reflux disease (NERD), 8 esophageal hypersensitivity, 11 functional heartburn, and 24 healthy controls were included in the study. During endoscopy gastric juices from the patients were aspirated and their pH readings immediately recorded. Gastric juice samples were analyzed using Peptest, a lateral flow device containing 2 unique human monoclonal antibodies to detect any pepsin present in the gastric juice sample. The highest mean gastric pepsin concentration (0.865 mg/mL) and the lowest median gastric pH (1.4) was observed in the LA grade C/D group compared with the lowest mean gastric pepsin concentration (0.576 mg/mL) and the highest median gastric pH (2.5) seen in the NERD group. Comparing pH, the NERD patient group was significantly higher (P=0.0018 to P=0.0233) when compared with all other GERD patient groups. The basal gastric pepsin level in the healthy control group was comparable to literature values. There was good correlation and a significant linear relationship between the gastric pepsin level and gastric pH within the patient groups. The severity of the GERD disease is related to the lowest pH and the highest pepsin concentration in gastric juice.

Cough from the perspective of a gastroenterologist

Cough from the perspective of a gastroenterologist Abstract. Chronic cough can have numerous origins. The work-up of these conditions should always include a multidisciplinary approach to exclude other causes first (cardial, pulmonary, structural changes of pharynx and larynx, allergies, malignancy) before thinking of an upper GI pathology. Cough as an extra-esophageal manifestation of gastroesophageal reflux disease (GERD) is the most common gastroenterological condition. From a gastroenterologist's perspective eosinophilic esophagitis (EoE) and esophageal motility disorders are potential differential diagnosis. If other worrisome symptoms (weight loss, anemia, dysphagia) are present at the same time an endoscopic evaluation with esophago-gastro-duodenoscopy (EGD) should be performed first to exclude a malignancy. Hereby one should perform biopsies of the esophagus to exclude an eosinophilic esophagitis (EoE). If the macroscopic and histopathology results of the EGD are unremarkable a probatory trial of acid-suppressive therapy with proton pump inhibitors (PPIs) is the first-line therapeutic option. For non-responders to PPI-therapy functional diagnostics are the next step. With the help of ambulatory pH-impedance monitoring one can diagnose a non- erosive reflux disease and an esophageal hypersensitivity. An esophageal manometry can deliver relevant information about the physiological anti-reflux barrier and diagnose motility disorders of the esophagus. Surgical therapy (antireflux surgery) can be an option for selected patients with proven reflux associated cough refractory to medical therapy. The aim of this review is to give an overview over a possible diagnostic-therapeutic algorithm from a gastroenterologist's point of view to approach the symptom cough.