Gastro-oesophageal Reflux Events 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 Gastro-oesophageal Reflux Disease and Laryngopharyngeal Reflux - Use the Bottom up Approach

Most gastro-oesophageal reflux events are triggered by transient lower oesophageal sphincter relaxations (TLOSRs). Acid-related reflux disease with typical heartburn and reflux oesophagitis generally responds well to acid suppression with proton pump inhibitors (PPI), but treating non-acid and mixed gaseous reflux has proven more challenging.

Efficacy of surgical or endoscopic treatment of idiopathic achalasia: a systematic review and network meta-analysis

Treatment of achalasia has changed substantially over the past 20 years. Therapeutic options offered to patients vary, depending on access to both resources and expertise, and include pneumatic dilation (PD), laparoscopic Heller's myotomy (LHM), or per-oral endoscopic myotomy (POEM). Although there are head-to-head trials of these interventions, many of these are small and underpowered, so relative efficacy is unknown. We did a systematic review and network meta-analysis to try to resolve this uncertainty. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and Embase Classic from database inception up to June 11, 2020, for randomised controlled trials (RCTs) assessing the efficacy of POEM, LHM, or PD, compared with each other in adults with idiopathic achalasia. We extracted all data as dichotomous outcomes (treatment success or failure) after completion of therapy. We also extracted country of origin, number of centres, duration of follow-up, and primary outcome measure used to define treatment success or failure. Data were extracted for intention-to-treat analyses, with all dropouts assumed to be treatment failures (ie, symptomatic at final point of follow-up), wherever trial reporting allowed this. We pooled data using a random effects model, and assessed heterogeneity between studies using the I2 statistic. Risk of bias was examined for all studies. The primary outcome was efficacy, in terms of a dichotomous measure of treatment success or failure, after a minimum of 1 year of follow-up. Secondary outcomes were occurrence of perforation, adverse events, serious adverse events (including death), need for reintervention, need for surgery as a result of complications, development of gastro-oesophageal reflux, or erosive oesophagitis. Efficacy was reported as a pooled relative risk (RR) of treatment failure, with a 95% CI, for each comparison tested, and ranked by therapy according to P-score. Of 1044 studies initially assessed, nine were eligible RCTs, which comprised 911 participants in total. None of the nine studies were at low risk of bias. Of the 911 participants 372 (41%) participants were randomly assigned to LHM, 317 (35%) participants to PD, and 222 (24%) participants to POEM. Of the three strategies, POEM was ranked first (RR of failure of treatment 0·33, 95% CI 0·15-0·71; P-score 0·89), then LHM (RR 0·45, 0·26-0·78, P-score 0·61). There was moderate heterogeneity between studies (I2=61·5%). Both POEM and LHM were superior to PD on direct and indirect comparison, but neither was significantly more effective than the other. There were no significant differences in perforation rates, need for re-intervention or surgery, gastro-oesophageal reflux, erosive oesophagitis, or serious adverse events, but PD was less likely to lead to adverse events than POEM. POEM and LHM should be the preferred treatments for idiopathic achalasia. PD performed worst in terms of treatment success, and therefore its role in the management of patients with achalasia is less certain. None.

Frequency of gastroesophageal reflux disease in children with adenoid hypertrophy

ObjectivesRecent studies have suggested that the reflux of gastric contents can cause adenoid hypertrophy (AH). The frequency of gastro-oesophageal reflux disease (GERD) in this AH population is unknown, but according to studies using pH-metry it may be as high as 65%. The aim of this study was to estimate the frequency of GERD among children with AH. MethodsThis was a cross-sectional, multicentre, prospective study of children with AH selected for adenoidectomy. The diagnosis of AH was made by a single laryngologist using a flexible fiberscope. All children had 24-hr multichannel intraluminal pH-impedance (MII/pH) assessment. A GERD diagnosis was made using BioVIEW software analysis after manual review by a single investigator. Results38 consecutive patients (21 males, mean age 6.58 years) were enrolled in the study. GERD was diagnosed in 5 (13.2%) patients. A total of 1462 gastro-oesophageal reflux events (GERs) were detected by MII/pH and the majority (60.9%) were acidic. The only significant differences between the GERD-positive and GERD-negative groups were the total number of GERs, and the number of acid GERs. ConclusionIt is first study using MII/pH to assess the frequency of GERD in children with AH. The data suggest that GERD in children with AH seems to be not as common as it was previously raised. Further studies are needed to confirm these results.

Optimization of impedance-measured reflux events in GORD utilizing acid exposure time

BackgroundCombining impedance with pH monitoring improves the detection and characterization of gastro-oesophageal reflux (GOR), yet the two modalities frequently differ in GOR quantification. Ambulatory 24-h pH-impedance monitoring often reveals more significant oesophageal acid exposure than impedance-measured reflux activity in patients with symptomatic gastro-oesophageal reflux disease (GORD). The purpose of this study is to elucidate the discrepancies between these modalities by assessing the predictive accuracy of impedance compared to acid exposure standards.MethodsA single-institution, retrospective review of sequential 24-h pH-impedance results of 72 patients with symptomatic GOR off anti-secretory therapy was conducted. Reflux events measured by impedance were stratified by patient position and compared to oesophageal acid exposure time (AET). Oesophageal AET limits for GORD detection were utilized as gold standards to generate serial receiver operator characteristics (ROC) curves to assess the sensitivity and specificity of current impedance GORD detection limits and identify optimized impedance standards based on area under the curve (AUC) analysis.ResultsMean total AET time was 10.5% (± 9.9%), and 63.8% of patients had elevated AET. By impedance, median GOR frequency was 43 (IQR 21–68), and 22.2% exceeded conventional GOR frequency limits of normal. ROC curve analysis revealed the current impedance standard of > 73 GOR events has a sensitivity of 32.6% and specificity of 96.5% (AUC 0.74) for GORD detection. By AUC analysis, an impedance threshold of > 41 GOR events is optimal for GORD detection (sensitivity 69.6%, specificity 80.7%, AUC 0.83).ConclusionConventional impedance standards for abnormal GOR frequency are weakly sensitive for the detection of GORD, providing a possible explanation to discrepancies in AET and impedance interpretation. Lowering impedance-measured GOR frequency limits to > 41 optimizes sensitivity and specificity while increasing congruence between pH and impedance metrics.

Twenty-four-hour oesophageal pH studies in rural Eastern Cape Province, South Africa.

Recent studies in rural Eastern Cape Province, South Africa, have shown an increased number of non-acid gastro-oesophageal reflux events, an increase in baseline gastric pH compared with other published series, and evidence suggestive of duodenogastric reflux. There are no published data on oesophageal pH in this community or in Africa. To ascertain whether oesophageal pH in this rural community is within normal limits. We carried out 24-hour oesophageal pH/impedance studies on 91 participants. Analysis was carried out using computer software to determine 24-hour percentage times of oesophageal pH above 4, 5, 6, 7 and 8. Oesophageal pH during each episode of non-acid reflux was also recorded. Participants were from Canzibe in rural Eastern Cape. Of the studies, 72 were satisfactory and showed 24-hour percentage times with an oesophageal pH >6 of 69.3/35.12/51.16 (upright/supine/total); percentage times with a pH >7 were 12.66/3.44/8.86 and those with a pH >8 were 0.48/0.21/0.37. These results are within the range of other published series. Of episodes of non-acid reflux, 90.2% were associated with an oesophageal pH of 4 - 7. Baseline oesophageal pH is not significantly affected by the increased numbers of non-acid gastro-oesophageal reflux events reported in this community. If there is a pathogenic effect of non-acid reflux in the Eastern Cape, it does not appear to be mediated through raised oesophageal pH.

The effects of exogenous lipid on THP-1 cells: an in vitro model of airway aspiration?

Chronic inflammatory diseases of the airways are associated with gastro-oesophageal reflux (GOR) and aspiration events. The observation of lipid-laden macrophages (LLMs) within the airway may indicate aspiration secondary to GOR. The proposed mechanism, that lipid droplets from undigested or partially digested food are aspirated leading to accumulation in scavenging macrophages, led us to hypothesise that an activated population of LLMs could interact with other immune cells to induce bronchial inflammation.To test this, we generated an in vitro model using differentiated THP-1 cells, which were treated with a high-fat liquid feed.Here, we show that THP-1 cells can take up lipid from the high-fat feed independent of actin polymerisation or CD36-dependent phagocytosis. These cells did not exhibit M1 or M2 polarisation. Gene array analysis confirmed over 8000 genes were upregulated by at least twofold following high fat exposure, and IL-8 was the most upregulated gene. Pathway analysis revealed upregulation of genes known to be involved in chronic obstructive pulmonary disease (COPD) pathophysiology.We suggest that aspiration and macrophage phagocytosis may be important mechanisms in the aetiology of diseases such as COPD and cystic fibrosis that are characterised by high levels of IL-8 within the airways.

Pharyngeal pH alone is not reliable for the detection of pharyngeal reflux events: A study with oesophageal and pharyngeal pH-impedance monitoring.

Pharyngeal pH probes and pH-impedance catheters have been developed for the diagnosis of laryngo-pharyngeal reflux. To determine the reliability of pharyngeal pH alone for the detection of pharyngeal reflux events. 24-h pH-impedance recordings performed in 45 healthy subjects with a bifurcated probe for detection of pharyngeal and oesophageal reflux events were reviewed. Pharyngeal pH drops to below 4 and 5 were analysed for the simultaneous occurrence of pharyngeal reflux, gastro-oesophageal reflux, and swallows, according to impedance patterns. Only 7.0% of pharyngeal pH drops to below 5 identified with impedance corresponded to pharyngeal reflux, while 92.6% were related to swallows and 10.2 and 13.3% were associated with proximal and distal gastro-oesophageal reflux events, respectively. Of pharyngeal pH drops to below 4, 13.2% were related to pharyngeal reflux, 87.5% were related to swallows, and 18.1 and 21.5% were associated with proximal and distal gastro-oesophageal reflux events, respectively. This study demonstrates that pharyngeal pH alone is not reliable for the detection of pharyngeal reflux and that adding distal oesophageal pH analysis is not helpful. The only reliable analysis should take into account impedance patterns demonstrating the presence of pharyngeal reflux event preceded by a distal and proximal reflux event within the oesophagus.

Randomised clinical trial: effects of monotherapy with ADX10059, a mGluR5 inhibitor, on symptoms and reflux events in patients with gastro-oesophageal reflux disease

ADX10059, a metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulator, has been shown to reduce gastro-oesophageal reflux events and oesophageal acid exposure in patients with gastro-oesophageal reflux disease (GERD) and healthy subjects. To evaluate the effects of ADX10059 monotherapy for 2 weeks on symptom control in patients with GERD. This was a double-blind, placebo-controlled, multi-centre trial in GERD patients who were responders to proton pump inhibitors (PPIs). Following PPIs withdrawal, a 2-week baseline washout period was followed by 2-week treatment with either ADX10059 120 mg or placebo b.d. The primary clinical efficacy endpoint was the number of GERD symptom-free days in treatment week 2 compared with the last 7 days of baseline. The effect on reflux events using 24-h impedance-pH monitoring was also determined in a subset of 24 patients. The full analysis set comprised 103 patients ADX10059 (N= 50), Placebo (N=53). In treatment week 2, ADX10059 significantly increased GERD symptom-free days (P=0.045) and heartburn-free days (P=0.037), reduced antacid use (P=0.017), improved total symptom score (P=0.048) including subscale heartburn/regurgitation (P=0.007) and sleep disturbance because of GERD (P= 0.022). ADX10059 significantly reduced total (P=0.034) and acidic reflux events (P=0.003). ADX10059 was well tolerated. Most common adverse events for ADX10059 were mild to moderate dizziness 16% and vertigo 12% (placebo 4% and 2%). Inhibition of mGluR5 with ADX10059 monotherapy reduces reflux events and improves symptoms in GERD patients. This mechanism has promise for the management of GERD.

PWE-020 Symptoms and objective measurement of gastro-oesophageal reflux in adults with cystic fibrosis: interim report

Introduction The association between gastro-oesophageal reflux (GOR) and various respiratory disorders including cystic fibrosis (CF) is widely acknowledged. Although the exact nature of this relationship is uncertain, it is thought that reflux aspiration is a contributing factor in lung dysfunction in these patients. Patients with GOR typically report symptoms such as heartburn, regurgitation, and occasionally atypical symptoms such as cough. It has been hinted that GOR in CF patients may be “silent” making detection and treatment often difficult. We piloted a cross-sectional survey to gain a better understanding of the perception of GOR and its impact on lung function. Methods Consenting patients completed two validated questionnaires regarding GOR symptoms which were scored and ranked (Gastro-oesophageal Reflux Symptom Questionnaire and Reflux Symptom Index). Patients were stratified by score and divided into two pilot groups; SGOR (symptomatic-highest scores) and AGOR (asymptomatic-lowest scores). Both groups underwent 24-h multiple intraluminal impedance/pH metry (MII) and high-resolution manometry (HRM) for positioning of MII probe. MII studies were assessed for the number of GOR events, proximal reflux events (PREs), and total proximal bolus exposure (TPBE). Patients remained on all current medication including PPIs. Clinical data were collected and compared retrospectively including most recent lung function results (FEV1). Result 53/110 patients completed questionnaires and 10 from each group were invited to undergo investigation—11 were completed successfully (age 18–55 years; four male, seven female; seven SGOR, four AGOR). There was little difference in the mean number of events between the groups (range 16–75, mean—SGOR 38, AGOR 42; (normal on PPI=48, off PPI=73)). There was no correlation between symptom scores (SS) and number of GOR events but there was a moderate negative correlation between the number of GOR events/FEV1. There was no significant difference in the mean number of PREs between the groups (range 1–31; mean SGOR=11, AGOR=22). TPBE ranged from 0.2–342 s. No correlation was shown between; number of PREs/SS, number of PREs/FEV1 and TPBE/FEV1. Conclusion This small pilot study indicated that CF patients demonstrate impaired awareness of GOR and supports the theory that GOR is associated with poorer lung function. While there was no significant difference in the number of PREs between the groups, levels were higher in the AGOR group. This suggests that CF patients have poor perception of proximal reflux, which could increase the likelihood of aspiration. Based on these findings we aim to continue the survey to gain a more comprehensive assessment of the perception of GOR in adults with CF.

Correlation between gastric pH and gastro‐oesophageal reflux contents: ambulatory pH‐impedance monitoring results

Gastro-oesophageal reflux events should be related to gastric contents. The goal of this study was to determine the relationship between gastric pH and the nature of reflux events. Ambulatory oesophageal pH-impedance and gastric pH monitoring was performed in 41 patients [29 off and 12 on proton pump inhibitor (PPI) therapy] and 12 controls. The mean gastric pH was measured within 2 min around the reflux episodes, 10 cm below the cardia. Acid reflux events occurred more frequently at gastric pH <4 (89%) than non-acid reflux events (63%, P < 0.0001). Acid reflux events extended more frequently 15 cm above the lower oesophageal sphincter (LOS; 34%) than non-acid reflux episodes (24%, P = 0.005). Gastric pH was significantly lower during interprandial reflux events than during postprandial ones in the three groups (P < 0.001). A positive correlation was found between gastric pH and the nadir oesophageal pH during reflux events in the three groups: this correlation was more significant in patients on PPI therapy. We conclude that most acid and non-acid reflux episodes occur at acid gastric pH, as measured 10 cm below the LOS. This measure does not appear a good predictor of the pH of reflux events.

Correlation between preterm apnoeas and acid/non-acid gastro-oesophageal reflux (GOR) or other intra-oesophageal events identified by simultaneous pH-impedance and polysomnography

Introduction. The evidence of a correlation between preterm apnoeas (PA) and gastro-oesophageal reflux (GOR) remain difficult also because of the technical difficult in the demonstration of some events us non-acid GORa and deglutition possibly related to PA. Our aim was to evaluate the correlation between intra-oesophageal events (acid(A)/non-acid(NA) GOR, deglutition) and PA.

Acid and Nonacid Gastro‐oesophageal Reflux in Neurologically Impaired Children

The diagnosis of gastro-oesophageal reflux (GOR) is more difficult in children with neurological impairment because symptoms are often less interpretable and frequently go undetected. The use of combined pH and multiple intraluminal impedance allows for the detection of both acid (pH < 4) and nonacid (pH > 4) GOR episodes, in addition to the height of the refluxate and the total acid and bolus clearance time in this cohort. Sixteen neurologically impaired children (9 were fed nasogastrically, 7 were fed orally) underwent 12-hour combined pH and multiple intraluminal impedance. There were a total of 425 reflux episodes during the study period, of which 239 (56.2%) were nonacid. The median of reflux episodes per hour was 1.8 (range, 0.2-6.3/h). The median height of the refluxate was 1.5 channels (range, 1.1-2.9); and 71.3% of reflux episodes reached the upper oesophagus, of which 52.4% were nonacid reflux events. On average there were more GOR events (both acid and nonacid) in the children who were fed via a nasogastric tube, and the median height of refluxate was also higher in this group. However, the median acid clearance time was longer (both proximal and distal) in the children who were fed orally (28.6 s vs 16.2 s proximally; 67.9 s vs 38.3 s distally). The median acid clearance time (21.7 s proximally; 39.5 s distally) was longer when compared with bolus clearance (14.9 s). More than half of the reflux events in neurologically impaired children are nonacidic and would therefore go undetected by conventional pH metry. There are more reflux events in children fed nasogastrically than oral-fed children.

Ambulatory 24‐h oesophageal impedance–pH recordings: reliability of automatic analysis for gastro‐oesophageal reflux assessment

Oesophageal pH-impedance monitoring allows detection of acid and non-acid gastro-oesophageal reflux (GOR) events. Visual analysis of impedance recording requires expertise. Our aim was to evaluate the efficacy of an automated analysis for GOR assessment. Seventy-three patients with suspected GORD underwent 24-h oesophageal pH-impedance monitoring. Recordings analysis was performed visually (V) and automatically using Autoscan function (AS) of Bioview software. A symptom index (SI) > or =50% was considered for a significant association between symptoms and reflux events. AS analysis detected more reflux events, especially non-acid, liquid, pure gas and proximal events. Detection of oesophageal acid exposure and acid reflux events was similar with both analyses. Agreement between V and AS analysis was good (Kendall's coefficient W > 0.750, P < 0.01) for all parameters. During pH-impedance studies, 65 patients reported symptoms. As compared to visual analysis, the sensitivity and specificity of a positive SI determined by AS were respectively 85.7% and 80% for all reflux events, 100% and 98% for acid reflux and 33% and 87.5% for non-acid reflux. Despite good agreement with visual analysis, automatic analysis overestimates the number of non-acid reflux events. Visual analysis remains the gold standard to detect an association between symptoms and non-acid reflux events.

Detection of bile reflux: in vivo validation of the Bilitec fibreoptic system *

The Bilitec ambulatory bile reflux monitor is advocated for the assessment of bile reflux. However, it has only been validated by bench top (in vitro) studies. This in vivo study used controlled 'iatrogenic' episodes of bile reflux to determine the ability of the Bilitec system to detect bile acids in the oesophageal lumen. At least 10 ml of fluid was aspirated from the stomach of each of 32 patients, and analysed quantitatively for total bile acids (TBA) and total bilirubin (TB). An in vitro assessment of this fluid with the Bilitec probe was performed initially. The Bilitec probe was then sited in the distal oesophagus, and the gastric fluid was introduced into the mid-oesophagus, through a naso-oesophageal tube, as a series of 10-ml volumes of varying dilutions (1:8, 1:4, 1:2, undiluted) to simulate gastro-oesophageal reflux events. Intraoesophageal bilirubin absorbance was compared with TBA and TB for each dilution. Both TBA and TB values correlated strongly with bilirubin absorbance in vitro (r = 0.83, p < 0.0001 and r = 0.82, p < 0.0001 respectively). However, this relationship was weaker in vivo (r = 0.64, p = 0.0001 and r = 0.68, p < 0.0001 respectively). Of the dilutions which contained potentially injurious concentrations of bile acid (>1 mmol/L), 77% were associated with absorbance >0.14 (currently accepted absorbance threshold for oesophageal bile reflux). Although in vitro sensitivity of the Bilitec probe to bile acids was excellent, in vivo sensitivity was less reliable, and 23% of significant 'bile reflux' episodes did not exceed the currently recommended Bilitec absorbance threshold for bile reflux. In contrast, false-positive results were unlikely. These findings suggest that the overall accuracy of the Bilitec system is probably sufficient for clinical use, although this method is not sufficiently reliable to be regarded as the gold standard for the evaluation of duodeno-oesophageal reflux.