Role Of Reflux Research Articles

Role of Reflux in the Pathogenesis of Eosinophilic Esophagitis: Comprehensive Appraisal With Off- and On PPI Impedance-pH Monitoring.

Role of reflux and mechanisms of response to proton pump inhibitor (PPI) therapy in eosinophilic esophagitis (EoE) have not yet been fully elucidated. Comprehensive assessment by impedance-pH monitoring could clarify these issues. Prospective multicenter study comparing EoE patients with healthy controls and gastroesophageal reflux disease cases. Patients with EoE were evaluated off- and on PPI; responsiveness was assessed by histology. Impedance-pH appraisal included chemical clearance, assessed with the postreflux swallow-induced peristaltic wave (PSPW) index, and mucosal integrity measured with mean nocturnal baseline impedance (MNBI). Sixty consecutive patients with EoE were compared with 60 age- and sex-matched healthy controls and 60 subjects with gastroesophageal reflux disease. The number of total refluxes was higher, while the PSPW index was lower in patients with EoE than in healthy controls. Off PPI, a lower MNBI gradient between the mid and distal esophagus distinguished 20 patients with PPI-refractory EoE from 40 patients with PPI-responsive EoE and was a predictor of PPI failure. On PPI, a lower PSPW index was the sole reflux parameter distinguishing PPI-refractory from PPI-responsive EoE; all reflux parameters improved in PPI-responsive patients, whereas the PSPW index was not modified in PPI-refractory cases and was independently associated with PPI-responsiveness. MNBI in the distal and mid esophagus improved much more in PPI-responsive than in PPI-refractory EoE. Reflux plays a role in the pathogenesis of EoE, more relevant in PPI-responsive cases. Low impedance gradient between the mid and distal esophagus may be useful to predict PPI refractoriness. PPIs mainly act by improving chemical clearance, i.e., by an antireflux action supporting long-term prescription in PPI-responsive EoE.

Mo1135 – Role of Reflux in the Pathogenesis of Eosinophilic Esophagitis - Comprehensive Appraisal with Off- and On-Ppi Impedance-Ph Monitoring

Mo1135 – Role of Reflux in the Pathogenesis of Eosinophilic Esophagitis - Comprehensive Appraisal with Off- and On-Ppi Impedance-Ph Monitoring

The Role of Reflux in Childhood Otorhinolaryngological Disorders

This article seeks to review the current literature on the role of laryngopharyngeal reflux in the development of various disorders of the ear, nose and throat in infants and children including otitis media, chronic rhinosinusitis and airway disorders. The aim is to guide the otolaryngology clinician in investigation and management of reflux and to identify priorities for future research in this area. Many otolaryngological disorders coexist with reflux more often than might be expected by chance, but evidence of causality is weak. Although many otolaryngologists are convinced that treatment of reflux can make a significant difference to the clinical course of many upper airway disorders, the evidence to support this is lacking. In part, this is due to inadequate tools for describing the symptoms and endoscopic signs of laryngopharyngeal reflux and the lack of a sensitive, specific and reliable objective test. Further research demonstrating simple associations between otolaryngological diseases and reflux is unlikely to be of much value. Instead, researchers should concentrate their efforts on studies to develop and validate better means of recording symptoms and signs of laryngopharyngeal reflux and investigating the clinical utility of salivary pepsin, oropharyngeal pH monitoring and multichannel intraluminal impedance.

Longitudinal study of gastroesophageal reflux and erosive tooth wear

BackgroundApproximately 60% of patients presenting to dentists with erosive tooth wear have significant gastroesophageal reflux (GERD), despite minor reflux symptoms. No longitudinal studies of reflux-associated erosive tooth wear and of reflux characteristics have been reported to date.The aim of this study was to characterize the longitudinal course of GERD and of associated erosive tooth wear, as well as factors predictive of its progression, in a large group of patients.MethodsSeventy-two patients presenting to dentists with clinically significant erosive tooth wear and increased esophageal acid exposure by 24-h multichannel intraluminal pH-impedance measurement (MII-pH) were re-assessed clinically and by MII-pH after 1 year treatment with esomeprazole 20 mg twice-daily. Predictive factors for erosive tooth wear were assessed by logistic regression.ResultsAt follow-up, no further progression in erosive tooth wear was observed in 53 (74%) of patients. The percentage of time with a pH < 4, the number of acid reflux episodes and the percentage of proximal esophageal reflux off-PPI did not change significantly after one year, but the number of weakly acidic reflux episodes decreased significantly in the large subgroup without progression. None of the baseline demographic, clinical, endoscopic or esophageal acid exposure characteristics were significantly associated with progression of erosive tooth wear at follow-up.ConclusionsIn this longitudinal study in patients with erosive tooth wear and oligosymptomatic GERD receiving esomeprazole for one year, erosive tooth wear did not progress further in the majority of patients. Background acidic esophageal reflux exposure appeared stable over time, whereas weakly acidic exposure decreased significantly in patients without erosion progression. MII-pH measurements on-PPI and with healthy controls will be useful in the further elucidation of the causal role of reflux in erosive tooth wear.Trial registrationClinicalTrials.gov, retrospectively registered: NCT02087345.

Gastroesophageal reflux disease and the presence of pepsin in the tears

The nasolacrimal duct in association with the lacrimal puncta, lacrimal canaliculi and lacrimal sac functions to collect and drain the tear film into the nasal cavity at the inferior nasal meatus where a fold of nasal mucosa, the so-called valve of Hasner, prevents mucous from entering the nose. High-resolution computed tomography demonstrated air inside the sac and nasolacrimal duct in approximately 29.3% of healthy patients suggesting that the system is not completely competent and that air and secretions might reach the precorneal film.Gastroesophageal reflux disease may contribute to dacryostenosis and subsequent primary acquired nasolacrimal duct obstruction. However a cause-effect relationship is unclear and only presumptive unless the presence of pepsin in tears can be demonstrated. Gastroesophageal and extra-esophageal reflux could reach the tear film via the nasolacrimal duct in a retrograde fashion and the middle ear via the Eustachian tube. We postulated that the ascending products of gastroesophageal reflux could cause edema of the nasolacrimal duct mucosa, which might progress to fibrosis and chronic inflammation and, ultimately, complete obstruction of the duct with epiphora.The role of reflux in the initial phase of this pathophysiological mechanisms could be demonstrated indirectly by pepsin. By contrast, the development of dacryostenosis blocking the passage of the nasolacrimal duct and thereby preventing pepsin from reaching the lacrimal film failed to explain the influence of gastroesophageal reflux disease with certainty.

477 Clinical Implications of Impedance Monitoring in Suspected Extraesophageal Reflux: Can the Traditional Physiologic Parameters Predict Impedance Results?

LES resting pressure compared to non-IPF patients (14.1 [4-32.5] vs. 16.7 [4-37.2]; p= 0.0999). Mean contraction amplitude in the distal and proximal esophagus were slightly higher in IPF compared to non-IPF patients (92.4 [40-190] vs. 84 [35-170] and 90.6 [10210] vs. 79.9 [10-210], respectively; p=ns), but the difference was not significant. In contrast, IPF patients had significantly higher (p<0.01) esophageal acid exposure (9.25[4.7-15.4] vs. 3.3[1.4-7.4] vs. 0.7[0-2.4.2]), number of acid (45[23-55] vs. 32[19-44] vs. 18[10-31]), weakly-acidic (34[19-43] vs. 21[11-33]) vs. 18[15-28]) and proximal reflux events (51[26.565.5] vs. 20[9.5-34.5] vs. 9[5-20]) compared to non-IPF patients and HVs. Pulmonary fibrosis HRCT-scores correlated well with reflux episodes in both distal (r2=0.567) and proximal (r2=0.6323) esophagus. Patients with IPF had more bile acids and pepsin (p<0.001) in BAL (62% and 67%) and saliva (61% and 68%) than non-IPF patients (40% and 40% in BAL, 33% and 36% in saliva) and controls (0% and 0% in both BAL and saliva). Conclusion: Increased acid and weakly acidic GER as well as more reflux reaching the proximal esophagus are prevalent in IPF. Patients with IPF have a relevant risk of gastric aspiration (increased bile acids and pepsin in saliva) or definite gastric aspiration (bile acids or pepsin in BAL). Outcome studies with intense anti-reflux therapy are needed to confirm the deleterious role of reflux in IPF progression.

Effects of Obstructive Sleep Apnea and Gastroesophageal Reflux Disease on Asthma Control in Obesity

Background. Obesity is a risk factor for asthma. Obese asthmatics often have poor asthma control and respond poorly to therapy. It has been suggested that co-morbidities associated with obesity, such as reflux and obstructive sleep apnea, could be important factors contributing to poor asthma control in obese patients. Objectives. The purpose of this study was to determine if (1) reflux and/or (2) symptoms of sleep apnea contribute to poor asthma control in obesity. Methods. We studied asthmatic subjects participating in a trial of reflux treatment. Participants underwent baseline evaluation of asthma symptoms and lung function. Overall 304 participants underwent esophageal pH probe testing; 246 participants were evaluated for obstructive sleep apnea symptoms. Results. Of 402 participants in this trial, 51% were obese. Role of reflux in asthma control. Those with higher body mass index (BMI) reported a higher prevalence of reflux symptoms, but the prevalence of pH probe acid reflux was similar in all groups. Reflux was not associated with measures of asthma control in obese patients. Role of obstructive sleep apnea in asthma control. Symptoms and self-report of obstructive sleep apnea were more common with increasing BMI and associated with worse asthma control as measured by the Juniper Asthma Control questionnaire and Asthma Symptom Utility Index. Conclusions. Our data suggest that obstructive sleep apnea, but not gastroesophageal reflux disease, may contribute significantly to poor asthma control in obese patients.

Role of Reflux in Tracheoesophageal Fistula Problems after Laryngectomy

The purpose of this 2-year prospective nonrandomized study was to investigate the relationship between pathological supraesophageal reflux and the occurrence of speech fistula complications, especially severe fistula enlargement, in patients who underwent total laryngectomy and prosthetic voice restoration. We objectively assessed the presence of reflux disease using 24-hour dual-probe pH monitoring in 60 laryngectomized patients, correlated the incidence of tracheoesophageal fistula complications with the severity of reflux, and assessed the risk of problems by determining the absolute number of reflux events at the level of the speech fistula, the reflux area index score, and the DeMeester score. All patients with fistula enlargement showed highly pathological results in the diagnostic tests for reflux disease. Depending on reflux severity, the relative risk of developing fistula complications was up to 10 times higher for these patients. We found a significant correlation between the occurrence of tracheoesophageal fistula complications and the severity of supraesophageal reflux. Potential chronic irritation of the esophageal and tracheal mucosa can possibly contribute to the development of these problems. If the presence of reflux disease has been confirmed by 24-hour dual-probe pH monitoring, patients with fistula complications should be treated with proton pump inhibitors.

Carditis in patients with gastro-oesophageal reflux disease: results of a controlled study based on both endoscopy and 24-h oesophageal pH monitoring.

There are conflicting reports on the role of gastro-oesophageal reflux disease (GERD) and Helicobacter pylori infection in the aetiology of carditis. The role of reflux and H. pylori infection in causing carditis was assessed in 113 consecutive patients with GERD and in 25 controls. All subjects underwent endoscopy and pH test and carditis was diagnosed on biopsies taken across the squamocolumnar junction. Helicobacter pylori was assessed by histology and rapid urease test. GERD was diagnosed by endoscopic oesophagitis or abnormal pH test. Carditis was detected in 53 of 71 GERD patients and in 15 of 20 controls. Among patients, 18 showed absent, 39 mild and 14 marked cardia inflammation and their H. pylori infection rates were 17, 23 and 57%, respectively (P < 0.025). Most patients with carditis (68%) lacked H. pylori infection. pH-metry was abnormal in 15 of 18 patients with normal cardia, 33 of 39 with mild carditis and 12 of 14 with marked inflammation. Carditis is a frequent finding in GERD and controls. Mild, non-active carditis is frequent in GERD patients. Marked inflammation is associated with both H. pylori and abnormal pH testing. Thus, both GERD and H. pylori infection may play a role in inducing carditis.

Ambulatory intraesophageal bilirubin monitoring in Japanese patients with gastroesophageal reflux.

The role of reflux of duodenal contents in gastroesophageal reflux in Japanese patients, which may be different from that in Western patients, was studied. Intraesophageal pH and the bilirubin concentration were monitored, using the Bilitec 2000, in 43 patients with reflux symptoms and 10 normal volunteers. The percentage of the time that spectrophotometric absorbance was 0.15 or more and pH was less than 4.0 was defined as the holding times (HTs) of bilirubin and acid, respectively. Severity of esophagitis was classified using the Savary-Miller (S-M) classification. Esophagitis was present in 37 patients; 5, 10, 13, and 9 patients had S-M grades 1, 2, 3, and 4, respectively. Both HTs in the volunteers were less than 5%. Bilirubin HT was more than 5% in 3 of the 6 patients without esophagitis, but the acid HT was less than 5% in these 6 patients. Acid HT was less than 5% in 4, 2, 2, and 2 patients with S-M grades 1, 2, 3, and 4, respectively. Bilirubin HT was less than 5% in 1 patient with S-M grade 2 esophagitis. Bilirubin HT in patients with S-M grades 3 and 4 esophagitis (50.9 +/- 5.8%) was higher than that in grades 1 and 2 (14.9 +/- 2.9%) (P < 0.0001), but this was not so for acid HT. In 32 patients, bilirubin HT exceeded acid HT. Bilirubin HT did not correlate with acid HT. Duodenogastroesophageal reflux occurred independently of and exceeded acid reflux. The amount of duodenogastroesophageal reflux correlated with the severity of esophagitis.

Pattern of ambulatory pharyngo-oesophageal motility and pH-metry in healthy volunteers.

Oesophago-pharyngeal reflux is widely accepted as an aetiological factor in many laryngeal and lower respiratory tract diseases. This study aims to establish normal reference ranges for pharyngo-oesophageal pH and pressure. Twenty-five asymptomatic healthy volunteers underwent ambulatory pharyngo-oesophageal pressure and pH-metry. Acid exposure times were very low. Only one subject showed any evidence of oesophago-pharyngeal reflux during recumbency. Two distinct upper oesophageal sphincter pressure patterns were observed during recumbency-one with episodic dry swallows and moderate tonic pressures, the other with almost complete manometric quiescence. Negative results, i.e. the exclusion of abnormal cervical reflux, appear to be more achievable than quantifiable positive results, but this is not absolutely clear from our results. Categorisation of an individual as having abnormal upper pH-metry requires use of a synchronous pharyngeal probe. pH-metry is likely to be of value in establishing the role of reflux in relation to laryngeal or respiratory disease.

The futility of raffinate reflux revisited

AbstractThe role of reflux in equilibrium separation processes has been examined from a mechanistic viewpoint. The raffinate reflux — presaturation of solvent with raffinate in a separate unit (presaturator) — has been demonstrated to be futile in the past, considering the stages to be ideal. We have examined the utility of raffinate‐like reflux in all the equilibrium separation processes. The nature of mass transfer in these processes with and without presaturator and its implications in the design and analysis have been presented.

Gastroesophageal reflux after distal gastrectomy: possible significance of the angle of His

Objective: We investigated whether the angle of His influences gastroesophageal reflux after distal gastrectomy. Methods: Thirty-eight patients having distal gastrectomy and 10 controls underwent upper gastroesophageal fluoroscopy to measure the angle of His, and gastroesophageal reflux was assessed by scintigraphy. The association between scintigraphic reflux and the angle of His was then evaluated. Results: In distal gastrectomy patients with and without reflux symptoms, the angle was 108.82 ± 21.88° and 96.07 ± 13.25°, respectively; it was 74.14 ± 10.85° in the controls. The angle was significantly larger in the patients than in the controls ( p < 0.01). In addition, the angle in the symptomatic gastrectomy group tended to be larger than in the asymptomatic group. The angle was also significantly larger in patients with a scintigraphic reflux index ≥6% than in those with an index <6% ( p < 0.05). Conclusions: These findings suggest that the angle of His plays a role in reflux after distal gastrectomy and that the severity of reflux may be estimated by measuring this angle.

Gastroesophageal reflux.

Preview Although heartburn is the most common symptom of gastroesophageal reflux, many patients with reflux have other, more obscure manifestations. Recognition of all potential signs and symptoms of reflux is important for expeditious management. This article focuses on these atypical presentations and discusses how treatment can be tailored to the specific pathophysiologic mechanism involved.

Metabolism of Carcinogenic Nitrosamines in the Rat and Human Esophagus and Induction of Esophageal Adenocarcinoma in Rats

The mechanism is discussed by which certain nitrosamines induce esophageal papillomas and squamous cancer in rats, and some evidence is presented for the view that nitrosamines also induce the same cancer in humans, especially in China and South Africa. Studies on the metabolism of nitrosamines by cytochrome P450 isozymes in rat and human esophagus, including the activation reactions of formaldehyde and pentaldehyde formation from methyl-n-amylnitrosamine (MNAN), are reviewed. These reactions are catalyzed by microsomes from the rat and human esophagus, probably because these microsomes contain specific cytochrome P450 isozymes. Evidence is reviewed for the occurrence of nitrosamines related to MNAN in fungus-infected corn. The incidence of esophageal adenocarcinoma is rising in Western countries. The precursor lesion, Barrett's esophagus, is associated with colon cancer, suggesting a role for bile salts in the induction of the esophageal tumor. Studies are described in which rats were subjected to esophago-duodenostomy (joining the duodenum to the esophagus) and then treated with nitrosamines that normally induce esophageal squamous cancer. Adenocarcinomas of the lower esophagus were induced as well as Barrett's esophagus (under one set of conditions). Feeding a high-fat diet with this system increased the incidence of esophageal adenocarcinoma. This tumor was not induced when the operation was changed to esophago-gastroplasty (widening the lower esophageal sphincter). These results support a role of reflux of duodenal contents (including bile and pancreatic juice) rather than of gastric contents in the etiology of human esophageal adenocarcinoma.

Hiccups and Achalasia

Excerpt Although esophageal disorders have been considered to cause hiccups (1, 2), the poor response of hiccups to anti-reflux surgery has led some investigators to question the role of reflux in ...

Clinical relevance of gastroduodenal dysfunction in reflux esophagitis.

This review critically evaluates the gastroduodenal factors that may play a clinically relevant role in the pathogenesis of reflux esophagitis. The gastroesophageal pressure gradient is of obvious importance, but the role of gastric contraction/relaxation is poorly understood. The intragastric volume, as well as the factors that influence it, could theoretically play a role in gastroesophageal reflux (GER). For example, suppression of gastric emptying and gastric motility would be expected to increase GER, and treatment with gastrokinetic agents appears to provide symptomatic improvement. However, only a fraction of patients with GER have delayed gastric emptying, and there is no correlation between either subjective epigastric fullness or esophagitis on one hand and gastric emptying on the other hand. Gastric acid and pepsin, and possibly the hypersecretion of acid, play a pivotal role in reflux esophagitis, as demonstrated by the efficacy of the treatment with histamine H2 antagonists and antacids. Other important factors in experimental esophagitis are duodenogastric reflux, the presence of bile acids in the gastric contents, as well as trypsin if the pH is alkaline. It is suggested that these important findings may lead to novel therapeutic approaches of reflux esophagitis.

P-Fimbrien pyelonephritogener Escherichia coli: Ihre Bedeutung für Reflux und renale Narbenbildung — eine Hypothese

An experimental pyelonephritis model was developed in monkeys (Macaca fascicularis) using P-fimbriated Escherichia coli as the infecting organism. The relevant receptor molecules for P-fimbriae were also shown to be present in Macaca fascicularis. Atraumatic administration of P-fimbriated E. coli into the ureter induced a ureteritis followed by acute and chronic pyelonephritis. The decisive role of P-fimbriae as an adhesive virulence factor was proven by the receptor blockade of P-fimbriae-mediated bacterial adhesion by a synthetic receptor analogue (alpha-D-Galp-(1-4)-beta-D-Galp-1-OMe), which was administered into the ureter together with the challenge bacteria. On the basis of these and other findings, the role of reflux and pyelonephritis in relation to renal scarring is discussed in this paper. It is proposed that minor transitional vesicoureteral reflux together with the adhesive property of P-fimbriated E. coli and their ability to induce ureteritis might constitute an alternative mechanism to gross reflux by which bacteria ascend to the kidney. These findings and the fact that intestinal colonization with P-fimbriated E. coli coincides with the disease have opened up new prophylactic and therapeutic possibilities.