Application of Lyon Consensus criteria for GORD diagnosis: evaluation of conventional and new impedance-pH parameters.

OBJECTIVE: To validate Lyon Consensus criteria for diagnosing gastro-oesophageal reflux disease (GORD) by reflux monitoring. DESIGN: Manual review of impedance-pH tracings from patients with proton pump inhibitor (PPI)-dependent heartburn, evaluated off PPI. Acid exposure time (AET) thresholds defined by the Lyon Consensus and impedance parameters were investigated, namely, total refluxes (TRs), postreflux swallow-induced peristaltic wave (PSPW) index and mean nocturnal baseline impedance (MNBI). RESULTS: The study included 488 patients, 178 (36%) with normal (<4%) AET, 89 (18%) with inconclusive (4%-6%) AET and 221 (45%) with abnormal (>6%) AET, alongside with 70 healthy controls. At receiver operating characteristic analysis, area under curve was 0.89, 0.95 and 0.89 for TRs, PSPW index and MNBI, respectively, and threshold values were 40, 50% and 2000 Ω; the 4% physiological AET threshold defined by the Lyon Consensus showed 100% specificity but 63% sensitivity. The thresholds defined for impedance parameters were validated against AET by means of ordered logistic regression, being in concordance with the 4% AET threshold (OR 2.5 for TRs, 18.9 for PSPW index and 5.7 for MNBI). TRs positivity and concordant PSPW index/MNBI positivity were found in 80%-90% of patients in the abnormal AET group, in 73%-74% of cases in the inconclusive AET group and in 28%-40% of cases in the group with normal AET. CONCLUSIONS: Our results show the overall validity of the Lyon Consensus approach to GORD diagnosis. Adding evaluation of impedance parameters, namely, TRs, PSPW index and MNBI to AET appraisal, substantially improves the diagnostic yield of reflux monitoring.

Reflux symptoms and oesophageal acidification in treated achalasia patients are often not reflux related.

OBJECTIVE: After treatment, achalasia patients often develop reflux symptoms. Aim of this case-control study was to investigate mechanisms underlying reflux symptoms in treated achalasia patients by analysing oesophageal function, acidification patterns and symptom perception. DESIGN: Forty treated achalasia patients (mean age 52.9 years; 27 (68%) men) were included, 20 patients with reflux symptoms (RS+; Gastro-Oesophageal Reflux Disease Questionnaire (GORDQ) ≥8) and 20 without reflux symptoms (RS-: GORDQ <8). Patients underwent measurements of oesophagogastric junction distensibility, high-resolution manometry, timed barium oesophagogram, 24 hours pH-impedance monitoring off acid-suppression and oesophageal perception for acid perfusion and distension. Presence of oesophagitis was assessed endoscopically. RESULTS: Total acid exposure time during 24 hours pH-impedance was not significantly different between patients with (RS+) and without (RS-) reflux symptoms. In RS+ patients, acid fermentation was higher than in RS- patients (RS+: mean 6.6% (95% CI 2.96% to 10.2%) vs RS-: 1.8% (95% CI -0.45% to 4.1%, p=0.03) as well as acid reflux with delayed clearance (RS+: 6% (95% CI 0.94% to 11%) vs RS-: 3.4% (95% CI -0.34% to 7.18%), p=0.051). Reflux symptoms were not related to acid in both groups, reflected by a low Symptom Index. RS+ patients were highly hypersensitive to acid, with a much shorter time to heartburn perception (RS+: 4 (2-6) vs RS-:30 (14-30) min, p<0.001) and a much higher symptom intensity (RS+: 7 (4.8-9) vs RS-: 0.5 (0-4.5) Visual Analogue Scale, p<0.001) during acid perfusion. They also had a lower threshold for mechanical stimulation. CONCLUSION: Reflux symptoms in treated achalasia are rarely caused by gastro-oesophageal reflux and most instances of oesophageal acidification are not reflux related. Instead, achalasia patients with post-treatment reflux symptoms demonstrate oesophageal hypersensitivity to chemical and mechanical stimuli, which may determine symptom generation.

British Society of Gastroenterology guidelines for oesophageal manometry and oesophageal reflux monitoring.

These guidelines on oesophageal manometry and gastro-oesophageal reflux monitoring supersede those produced in 2006. Since 2006 there have been significant technological advances, in particular, the development of high resolution manometry (HRM) and oesophageal impedance monitoring. The guidelines were developed by a guideline development group of patients and representatives of all the relevant professional groups using the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool. A systematic literature search was performed and the GRADE (Grading of Recommendations Assessment, Development and Evaluation) tool was used to evaluate the quality of evidence and decide on the strength of the recommendations made. Key strong recommendations are made regarding the benefit of: (i) HRM over standard manometry in the investigation of dysphagia and, in particular, in characterising achalasia, (ii) adjunctive testing with larger volumes of water or solids during HRM, (iii) oesophageal manometry prior to antireflux surgery, (iv) pH/impedance monitoring in patients with reflux symptoms not responding to high dose proton pump inhibitors and (v) pH monitoring in all patients with reflux symptoms responsive to proton pump inhibitors in whom surgery is planned, but combined pH/impedance monitoring in those not responsive to proton pump inhibitors in whom surgery is planned. This work has been endorsed by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG) under the auspices of the oesophageal section of the BSG.

Pepsin in saliva for the diagnosis of gastro-oesophageal reflux disease.

OBJECTIVE: Current diagnostic methods for gastro-oesophageal reflux disease (GORD) have moderate sensitivity/specificity and can be invasive and expensive. Pepsin detection in saliva has been proposed as an 'office-based' method for GORD diagnosis. The aims of this study were to establish normal values of salivary pepsin in healthy asymptomatic subjects and to determine its value to discriminate patients with reflux-related symptoms (GORD, hypersensitive oesophagus (HO)) from functional heartburn (FH). DESIGN: 100 asymptomatic controls and 111 patients with heartburn underwent MII-pH monitoring and simultaneous salivary pepsin determination on waking, after lunch and dinner. Cut-off value for pepsin positivity was 16 ng/mL. Patients were divided into GORD (increased acid exposure time (AET), n=58); HO (normal AET and + Symptom Association Probability (SAP), n=26) and FH (normal AET and-SAP, n=27). RESULTS: 1/3 of asymptomatic subjects had pepsin in saliva at low concentration (0(0-59)ng/mL). Patients with GORD and HO had higher prevalence and pepsin concentration than controls (HO, 237(52-311)ng/mL and GORD, 121(29-252)ng/mL)(p<0.05). Patients with FH had low prevalence and concentration of pepsin in saliva (0(0-40) ng/mL). A positive test had 78.6% sensitivity and 64.9% specificity for diagnosis of GORD+HO (likelihood ratio: 2.23). However, one positive sample with >210 ng/mL pepsin suggested presence of GORD+HO with 98.2% specificity (likelihood ratio: 25.1). Only 18/84 (21.4%) of GORD+HO patients had 3 negative samples. CONCLUSION: In patients with symptoms suggestive of GORD, salivary pepsin testing may complement questionnaires to assist office-based diagnosis. This may lessen the use of unnecessary antireflux therapy and the need for further invasive and expensive diagnostic methods.

Randomised clinical trial: the use of alginates during preinvestigation proton pump inhibitor wash-out and their impact on compliance and symptom burden.

BACKGROUND/AIMS: Investigation of gastro-oesophageal reflux disease is usually performed off proton pump inhibitors (PPIs). This can exacerbate symptoms, potentially impacting investigation accuracy if patients circumvent the preinvestigation instructions. There are no standard recommendations on how to manage PPI withdrawal. We aimed to assess the impact of structured alginate use on symptom burden. METHODS: Participants were already established on ≥4 weeks of PPI therapy and being referred for manometry and 24-hour pH/impedance testing. Preinvestigation instructions involved stopping PPIs and H2 receptor antagonists for 1 week, but antacids and alginates were allowed until the night before. Participants were randomised to follow these standard instructions (control group), or the same instructions with the provision of Gaviscon Advance to be taken four times daily (treatment group). The primary outcome assessed change in Gastro-Oesophageal Reflux Disease Health-Related Quality of Life Score. KEY RESULTS: Data for 48 patients were available for primary outcome assessment. While patients in the control group had a significant increase in symptoms (median difference 6.5, 95% CI (1 to 7), p=0.04), no change occurred in the treatment arm (median difference -1.5, 95% CI (-2, 3.5), p=0.54). There were no serious adverse events. CONCLUSIONS: Structured alginate use prevents symptom exacerbation during preinvestigation PPI wash-out. These findings are limited to the 1-week wash-out period but can benefit thousands of patients undergoing investigation for gastro-oesophageal reflux each year. Further research is required to assess this effect in other settings, such as sustained PPI deprescription. The trial was funded by Reckitt Benckiser. TRIAL REGISTRATION NUMBER: EudraCT registration 2019-004561-41.

BSPGHAN Motility Working Group position statement: paediatric multichannel intraluminal pH impedance monitoring-indications, methods and interpretation.

BACKGROUND: Combined pH-impedance monitoring has been suggested as the investigation of choice for diagnosing gastro-oesophageal reflux in children. Although it is superior to oesophageal pH monitoring in detecting all types of reflux episodes (acid, weakly acidic and alkaline) with the ability to evaluate symptom association with reflux events, it is still limited by the lack of true paediatric normal value and the high cost involved (equipment and personnel). OBJECTIVE: To produce a position statement on behalf of the Motility Working Group of the British Society of Paediatric Gastroenterology, Hepatology and Nutrition on the indications and practical application of combined oesophageal pH-impedance monitoring in children. METHODS: Up-to-date review of available evidence. RESULTS: This document provides a practical guide to clinician on indications, methods and results interpretation of paediatric multichannel intraluminal impedance pH (MII-pH). CONCLUSIONS: MII-pH is increasingly used by paediatricians as the diagnostic tool for assessing gastro-oesophageal reflux disease and symptom association. There is wide variation in paediatric practice and a need for standardised practice.

Clinical and pH study characteristics in reflux patients with and without ineffective oesophageal motility (IEM).

BACKGROUND: The aetiology and clinical impact of ineffective oesophageal motility (IEM) remain poorly understood, but the condition is thought to worsen supine gastro-oesophageal acid reflux (GERD). AIMS: In this retrospective cohort analysis of symptomatic patients with abnormal oesophageal acid exposure, we sought to determine any clinical or functional characteristics that would distinguish those with normal peristalsis from those with IEM, defined using the Chicago classification. We hypothesised that the impaired oesophageal clearance in IEM would be contributing to more severe degrees of pathological acid exposure, as well as clinical and endoscopic GERD severity. METHODS: Consecutive symptomatic patients with GERD underwent clinical, endoscopic and functional evaluation that included high-resolution impedance manometry (HRIM) and ambulatory pH monitoring performed 'off' acid suppressive therapy. RESULTS: Of the 114 patients with abnormal oesophageal acid exposure, 71 had normal oesophageal motility by HRIM and 43 were diagnosed with IEM (38% prevalence). Age, gender and symptom duration were similar between the two groups. Both groups had similar magnitude and frequency of symptoms, making a distinction clinically impossible. Endoscopically, the two groups had similar rates of erosive disease, hiatal hernia and Barrett's oesophagus. Ambulatory pH, proton pump inhibitor (PPI) dosage and PPI response rates were also similar. Nevertheless, patients with IEM had significantly more impairment of oesophageal clearance (mean 56.9±6.4) than those with normal motility (mean 32.4±5.0) (p<0.003). CONCLUSIONS: Symptomatic patients with IEM exhibit significant impairment of oesophageal clearance but are otherwise clinically indistinguishable from those with normal oesophageal motility and have a similar prevalence of erosive disease and pathological acid exposure.

Factors Affecting the Prevalence of Gastro-oesophageal Reflux in Childhood Corrosive Oesophageal Strictures.

BACKGROUND: Gastro-oesophageal reflux may accompany the corrosive oesophageal damage caused by the ingestion of corrosive substances and affect its treatment. The factors that affect the development of reflux in these cases and their effects on treatment still remain unclear. AIMS: Our aim is to investigate the prevalence of gastro-oesophageal reflux in children with corrosive oesophageal strictures, the risk factors affecting this prevalence and the effects of gastro-oesophageal reflux on treatment. STUDY DESIGN: Case-control study. METHODS: We enrolled 52 patients with oesophageal stricture due to corrosive substance ingestion who were referred to our clinic between 2003 and 2010. Groups, which were determined according to the presence of gastro-oesophageal reflux (GER), were compared with each other in terms of clinical findings, results of examination methods, characteristics of the stricture and success of the treatment. RESULTS: The total number of patients in our study was 52; 30 of them were male and 22 of them were female. The mean age of our study population was 4.2±2.88 years. Thirty-three patients had gastrooesophageal reflux (63.5%). Patients who had strictures caused by the ingestion of alkali substances were 1.6-times more likely to have reflux. There were no differences between patients with or without reflux in terms of number and localisation of strictures. Mean distance of stricture was longer in patients with reflux (3.7±1.8 cm) than in patients without (2.2±1.0 cm) (p<0.005). Only one patient among 17 who had a long stricture (≥4 cm) did not suffer from reflux. Patients with long stricture were 1.9-times more likely to have reflux. Dilatation treatment was successful in 69.6% of patients with reflux and in 78.9% of patients without. The mean treatment period was 8.41±6.1 months in patients with reflux and 8.21±8.4 months in the other group. There was no significant difference between groups in terms of frequency of dilatation and dilator diameters (p>0.05). CONCLUSION: Corrosive oesophageal stricture was usually accompanied by gastro-oesophageal reflux and the length of stricture is an important risk factor. Negative effects of reflux over dilatation treatment have not yet been demonstrated in the short-term. Nevertheless, this frequent rate of reflux may eventually increase the risk of oesophagitis and Barrett's oesophagus; therefore, we suggest that these effects should be prospectively evaluated in a large number of patients and these patients should be followed-up routinely in terms of the long-term effects of reflux.

Prevalence of gastro-oesophageal reflux disease with upper gastrointestinal symptoms without heartburn and regurgitation.

BACKGROUND: Symptomatically 'silent' gastro-oesophageal reflux disease (GORD) may be underdiagnosed. OBJECTIVE: To determine the prevalence of untreated GORD without heartburn and/or regurgitation in primary care. METHODS: Patients were included if they had frequent upper gastrointestinal symptoms and had not taken a proton pump inhibitor in the previous 2 months (Diamond study: NCT00291746). GORD was diagnosed based on the presence of reflux oesophagitis, pathological oesophageal acid exposure, and/or a positive symptom-acid association probability. Patients completed the Reflux Disease Questionnaire (RDQ) and were interviewed by physicians using a prespecified symptom checklist. RESULTS: GORD was diagnosed in 197 of 336 patients investigated. Heartburn and/or regurgitation were reported in 84.3% of patients with GORD during the physician interviews and in 93.4% of patients with GORD when using the RDQ. Of patients with heartburn and/or regurgitation not identified at physician interview, 58.1% (18/31) reported them at a 'troublesome' frequency and severity on the RDQ. Nine patients with GORD did not report heartburn or regurgitation either at interview or on the RDQ. CONCLUSIONS: Structured patient-completed questionnaires may help to identify patients with GORD not identified during physician interview. In a small proportion of consulting patients, heartburn and regurgitation may not be present in those with GORD.

The influence of the speed of food intake on multichannel impedance in patients with gastro-oesophageal reflux disease.

BACKGROUND: There is a general belief that gastro-oesophageal reflux increases after meals and especially following a rapid intake. OBJECTIVE: To evaluate the impact of rapid vs. slow food intake on gastro-oesophageal reflux disease (GORD) patients. MATERIALS AND METHODS: Forty-six GORD patients with heartburn and / or acid regurgitation once a week or more often common were included in this study. Participants were asked to eat the same standard meal within either 5 or 30 minutes under observation in a random order on 2 consecutive days. A total of 28 hours of recording were obtained by intraoesophageal impedance pH and number of liquid and mixed reflux episodes within 3 hours of the slow- and fast-eating postprandial periods were calculated. RESULTS: While all patients defined GORD symptoms, 10 (21.7%) had pathological 24-h intraoesophageal impedance measurement, 15 (32.6%) had pathological DeMeester and 21.7% had erosive oesophagitis. No difference has been shown according to the eating speed when all reflux episodes were taken together (754 vs. 733). Speed of food intake also did not have an impact on patients with normal vs. pathological 24-h intraoesophageal impedance or erosive vs. non-erosive. During the first postprandial hour, approximately half of the reflux events were non-acid, compared to 34.2% during the second hour and 26.8% during the third hour (p < 0.001). The number of acid reflux episodes was significantly higher than non-acid reflux especially during the second and third hours and in total for 3 hours. CONCLUSIONS: This first study addressing the effect of eating speed on reflux episodes in GORD patients did not support the general belief that reflux increases following fast eating. Acid and non-acid reflux were similar at the first postprandial hour, then acid reflux episodes were predominantly higher, which implicate the importance of acid pockets.

Management of the patient with incomplete response to PPI therapy.

Proton pump inhibitors (PPIs) remove most of the acid from the gastroesophageal refluxate. However, PPIs do not eliminate reflux and the response of specific GERD symptoms to PPI therapy depends on the degree to which acid drives those symptoms. PPIs are progressively less effective for heartburn, regurgitation, chest pain and extra-oesophageal symptoms. Hence, with an incomplete PPI response, obtaining an accurate history, detailing which symptoms are 'refractory' and exactly what evidence exists linking these symptoms to GERD is paramount. Reflux can continue to cause symptoms despite PPI therapy because of persistent acid reflux or weakly acidic reflux. Given these possibilities, diagnostic testing (pH or pH-impedance monitoring) becomes essential. Antireflux surgery is an alternative in patients if a clear relationship is established between persistent symptoms, particularly regurgitation, and reflux. Treating visceral hypersensitivity may also benefit the subset of GERD patients whose symptoms are driven by this mechanism.