Symptom Association Probability Research Articles

Non-Acid GERC: Pathogenesis, Diagnosis and Management

Total Recent investigations have highlighted the pivotal influence of non-acid reflux in the etiology of chronic cough associated with gastroesophageal reflux disease (GERC). Differentiation between acid and non- acid GERC is effectively achieved through esophageal pH monitoring, with non-acid reflux drawing attention for its linkage to non-standard symptoms and the intricacies involved in its management. The combination of multi-channel intraluminal impedance with pH monitoring (MII-PH) and its related metrics, including acid exposure time (AET), symptom association probability (SAP), and symptom index (SI), as well as the quantity, pH, nature of reflux, its spread, and acid clearance time, alongside innovative measures such as mean nocturnal baseline impedance (MNBI) and post- reflux induced peristaltic wave index (PSWPI), is pivotal in precisely delineating reflux patterns and identifying the temporal connection between non-acid reflux occurrences and episodes of coughing. The prevailing reliance on proton pump inhibitors (PPIs) for treatment has encountered constraints in effectively managing non-acid GERC, underscoring the necessity for personalized treatment modalities that confront the unique pathophysiology of non-acid GERC to ameliorate patient outcomes. As research continues to deepen our understanding and enhance treatment methods for this multifaceted condition, the pursuit of effective treatment strategies becomes crucial. Our review aims to delineate the spectrum of therapeutic options, advancements in diagnostics, and an improved grasp of the pathogenesis of non-acid GERD. The focus of this review is to further the advancement of patient care management and to inspire continued research in this intriguing domain of gastroenterology.

Study on Nocturnal Infant Crying Evaluation (NICE) and Reflux Disease (RED).

Nocturnal infant crying is often empirically treated with acid suppressants. The aim of this study was to evaluate the prevalence and characteristics of gastroesophageal reflux (GER) in infants with unexplained persistent crying. We enrolled all infants (0-12 months) referred for suspected GER disease who underwent esophageal impedance-pH monitoring (MII-pH) for unexplained persistent crying not improved by parental reassurance, dietary modification or alginate. Gastrointestinal malformation/surgery, neurological impairment and infections were exclusion criteria. Demographic and anthropometric parameters, GER symptoms and questionnaires (I-GERQ-R) and MII-pH data were recorded and analyzed. Normal MII-pH was defined when acid exposure was <3%, symptom index was <50% and symptom association probability was <95%. Acid exposure >5% and >10% was also considered. Statistical analysis was performed using Chi-Square and univariate and multivariable regression analysis. We included 50 infants (median age 3.5 months) who fulfilled the study criteria: 30 (60%) had normal MII-pH. I-GERQ-R score was abnormal in 33 (66%) infants, and 21/33 (64%) had normal MII-pH (p = 0.47). In the 26 (52%) infants with nocturnal crying, MII-pH was normal in 16 (54%) (p = 0.82). Associated regurgitation (>3 or >10 episodes/die) did not predict abnormal MII-pH (p = 0.74, p = 0.82, respectively). Univariate and multivariable regression analysis did not identify any clinical variable significantly associated with abnormal MII-pH. Infants with persistent unexplained and nocturnal crying should not be empirically treated with acid inhibitors.

Post-reflux swallow-induced peristaltic wave index: a new parameter for the identification of non-acid gastroesophageal reflux-related chronic cough.

The current available diagnostic criteria for gastroesophageal reflux-related chronic cough (GERC) dominated by non-acid reflux is imperfect. The post-reflux swallow-induced peristaltic wave index (PSPWI) is a parameter reflecting esophageal clearance function. This study aims to investigate its diagnostic value for non-acid GERC. This study sought to compare the diagnostic value of PSPWI in different types of GERC, particularly non-acid GERC, and explore the clinical significance of PSPWI in the diagnosis of non-acid GERC through diagnostic experiments. A retrospective analysis was performed based on 223 patients with suspected GERC who underwent multichannel intraluminal impedance-pH monitoring (MII-pH) in the outpatient clinic of our department from August 2016 to June 2021. Their clinical information, laboratory test results, and treatment responses were assessed and the underlying etiologies of chronic cough were categorized. The predictive value of the PSPWI in diagnosing different types of GERC, especially non-acid GERC, was analyzed and compared. A total of 195 patients with chronic cough who met the inclusion criteria underwent MII-pH monitoring. 143 patients had a definitive diagnosis of GERC, including 98 with acid GERC and 45 with non-acid GERC. The diagnostic value of PSPWI alone was moderate for GERC with an area under the working curve (AUC) 0.760, but poor for non-acid GERC with an AUC of 0.569. However, PSPWI < 39.8% combining with acid exposure time (AET) ⩽ 6.2% demonstrated a moderate diagnostic value for non-acid GERC, with an AUC of 0.722. When PSPWI < 39.8% combined with a non-acid reflux ratio >68.75%, the diagnostic value for non-acid GERC was improved (AUCROC = 0.80 versus AUCROC = 0.722, p < 0.05), which was significantly superior to non-acid symptom index (AUCROC = 0.804 versus AUCROC = 0.550, p < 0.05) and non-acid symptom association probability (AUCROC = 0.804 versus AUCROC = 0.571, p < 0.05). PSPWI < 39.8% and AET ⩽ 6.2% have demonstrated good diagnostic value for non-acid GERC. The diagnostic value was further improved when combined with non-acid reflux ratio >68.75%.

OGBN P20 A Clinician Delivered pH Manometry Service

Abstract Background Gastroesophageal reflux disease (GORD) has an influence on patients’ health related quality of life, affecting 20% of adults in high income countries (1)(2). Despite first line therapy, proton pump inhibitors, approximately 20-30% of patients have persistent symptoms (3). Anti-reflux surgery is by its very nature a lifestyle related procedure, thus there must be a robust and duplicatable method for assessment of the severity of symptoms to facilitate patient selection. We launched a clinician delivered high-resolution pH oesophageal manometry and ambulatory pH impedance service in January 2021 at our Specialist Anti-Reflux Centre. Here we present our preliminary data. Methods This is a retrospective analysis of patients who underwent ambulatory pH manometry within our department between January 2021 and June 2023. Analysis to date was undertaken of patient’s outcomes from their pH manometry. Patients with previous anti-reflux surgery were excluded. We reviewed those who were offered surgery versus those who were not. Each group had further analysis of the DeMeester score, Symptom Index (SI) and Symptom Association Probability (SAP). A two sample T-test was performed, with p&amp;lt;0.05 considered statistically significant. Results Of the 141 patients that underwent ambulatory pH manometry, 62% (n=88) had sufficient data for analysis. 33% (n=29) of these were subsequently offered surgical intervention; 14 underwent fundoplication (48%) and 12 LINX procedures (41%); the remaining patients, 1 referred for POEM, 1 awaited surgical planning and 1 required Gastroenterology review. Those who progressed to surgery had a greater DeMeester score than those who were not offered surgery (45.2 vs 28.5). Patients in the surgical group also had a higher mean SI than those in the non-surgical group (57.0% vs 38.6%, p=0.01), and higher SAP (94.1% vs 80.3%, p=0.03). Conclusions This clinician-led in-house clinic has had significant impact upon our service. It has enabled collation of quantitative data to facilitate the decision-making process in the provision of anti-reflux surgery, thus aiding appropriate patient selection. Going forward, further work is being undertaken into quality of life questionnaires post anti-reflux surgery, both before and after introduction of our new service.

Manual censoring of impedance tracings by the Wingate consensus reduces the number of impedance episodes, impacting on reflux categorization.

The Lyon consensus classifies the evidence of gastroesophageal reflux (GERD) based on endoscopic features and results of pH/impedance monitoring (pH-MII) including the post-reflux swallow-induced peristaltic wave index (PSPWI) and mean nocturnal baseline impedance (MNBI). The Wingate consensus established criteria to reduce inter-reviewer variability when assessing reflux episodes and PSPWI by impedance. This study aims to assess the influence of the Wingate criteria on the different pH-MII parameters obtained by automated analysis. Thirty consecutive pH-MII off PPI were reviewed according to Wingate criteria. Number of impedance episodes and PSPWI were compared before and after censoring from automatic analysis. Reflux categorization according to Lyon consensus between censored and uncensored data was compared. Pearson correlations between impedance parameters and censored episodes were calculated. Censoring the tracings significantly reduced the number of reflux episodes (66 [42-90.25] vs. 44.5 [21.5-61.5], p = 0.0105). Reasons for censoring were as follows: 1/ anterograde episode: 9.5 [6-13], 2/ impedance drop <50%: 1 [0-3], 3/ duration <4 s: 1 [0-2], 4/ <2 distal channels: 2.5 [1-4], and 5/ artifacts: 2 [1-5]. Censored episodes were in majority non-acid (16.5 [13-26.5] vs. 2 [0-4], p < 0.00001). Censoring altered the categorization of impedance episodes (<40 episodes, 6 vs. 13 for resp. uncensored vs. censored tracings, 40-80 episodes: 13 vs. 13, and >80 episodes: 11 vs. 4, p = 0.0264), but not the symptom index, the symptom association probability, or the categorization according to the Lyon consensus. Nevertheless, individual tracings were affected. The percentage of censored episodes was inversely correlated with the number of acidic impedance episodes (r = -0.62, p = 0.0002). Manual interpretation of impedance tracings based on the Wingate consensus reduces the number of impedance episodes, impacting on reflux categorization. Acidic reflux episodes are less likely to be censored, harboring a potential at improving automatic pH-MII analysis.

Improved diagnosis of reflux hypersensitivity.

Reflux hypersensitivity (RH) is characterized by normal esophageal exposure to acid and positive correlation of symptoms to reflux episodes. Positivity of Symptomatic Index (SI) and/or Symptom Association Probability (SAP) is used diagnostically, though experts support that concordance of both is needed. We evaluated differences among patients with RH and concordance of SI/SAP or not. Patients with typical reflux symptoms without previous GERD diagnosis, submitted simultaneously to Ph-Impedance off PPI and high resolution manometry were included. Self-response to PPI was evaluated. Patients showing SI and/or SAP positivity were considered having RH and further classified to definite RH if both SI/SAP were positive or indefinite if only one positive. Totally 2659 patients (M/F: 35.6%/64.7%, mean age: 45 ± 14) were included. Final diagnosis was; FH: 21.8%, RH: 29.3% (definite: 14.3%/indefinite: 15%), GERD: 36% and inconclusive GERD: 12.9%. Patients with definite RH showed increased total reflux time, total number of reflux episodes and length of hiatus hernia, and also numerically but not statistically significant increased rates of PPI responsiveness versus indefinite RH and decreased mean nocturnal baseline impedance. Moreover, they showed significantly increased rate of PPI response versus patients with functional heartburn (FH). Some PPI responsiveness is frequent among patients with RH as also with FH, and cannot discriminate those entities clinically when diagnosing RH using SI and/or SAP positive criterion. Patients with RH and SI/SAP concordance differ from patients without. Implementation of a strict RH definition (both SI and SAP positive) can better distinguish RH from FH and should be used in the future.

The Utility of Symptom Association Probability (SAP) in Predicting Outcome After Laparoscopic Fundoplication in Patients with Abnormal Esophageal Acid Exposure

IntroductionAbnormal DeMeester score on pH monitoring is a well-established predictor of favorable outcome after antireflux surgery (ARS). Esophageal pH monitoring also facilitates analysis of the temporal association between symptoms and reflux episodes. This association can be expressed with several symptom–reflux association indices with symptom association probability (SAP) being the most reliable. SAP is often used as an adjunct to DeMeester score during preoperative assessment of patients seeking ARS. However, data on the utility of SAP in predicting ARS outcome is limited. The aim of this study was to determine the utility of SAP as an adjunct to DeMeester score in predicting outcomes after fundoplication. MethodsRecords of patients who underwent primary fundoplication from 2015 to 2021 were reviewed. Patients with a preoperative DeMeester score >14.7 on Bravo pH monitoring were included. A SAP >95% was considered SAP-positive. Favorable outcome was defined as freedom from proton pump inhibitors (PPIs) and patient satisfaction at 1 year postoperatively. Outcomes were compared based on the presence and number of SAP-positive symptoms, individual typical and atypical SAP-positive symptoms, and within demographic, clinical, and reflux severity subgroups. ResultsThe final study population consisted of 597 patients (71.4% female) with a median (IQR) age of 59.0 (49–67). At a mean (SD) follow-up of 10.5 (8) months, 82.0% patients achieved favorable outcome (satisfaction and freedom from PPI), freedom from PPI was 91.7%, and satisfaction was 87.4%. SAP was positive in 430 (72.0%) patients, of which 221 (37.0%) had one SAP-positive symptom, 164 (27.5%) had two SAP-positive symptoms, and 45 (7.5%) had all three SAP-positive symptoms. There was no association between having at least one SAP-positive symptom and favorable outcome (p=0.767). There was no difference in favorable outcome between patients with one, two, or all SAP-positive symptoms (0.785). Outcomes were comparable for SAP-positive typical (p=0.873) and atypical symptoms (p=1.000) and all individual symptoms (p>0.05). Outcomes were also comparable within all subgroups (p>0.05). ConclusionSymptom association probability with an abnormal DeMeester score did not enhance the prediction of antireflux surgery outcome. These findings suggest that SAP should not be used in surgical decision-making in patients with objective evidence of reflux. Graphical Abstract [Display omitted]

Prevalence of Non-erosive Esophageal Phenotypes in Children: A European Multicenter Study

Since available data on pediatric non-erosive esophageal phenotypes (NEEPs) are scant, we investigated their prevalence and the phenotype-dependent treatment response in these children. Over a 5-year period, children with negative upper endoscopy, who underwent esophageal pH-impedance (off-therapy) for persisting symptoms not responsive to proton pump inhibitor (PPI)-treatment, were recruited. Based on the results of acid reflux index (RI) and symptom association probability (SAP), patients were categorized into: (1) abnormal RI (non-erosive reflux disease [NERD]), (2) normal RI and abnormal SAP (reflux hypersensitivity [RH]), (3) normal RI and normal SAP (functional heartburn [FH]), and (4) normal RI and not-reliable SAP (normal-RI-not otherwise-specified [normal-RI-NOS]). For each subgroup, treatment response was evaluated. Out of 2333 children who underwent esophageal pH-impedance, 68 cases, including 18 NERD, 14 RH, 26 FH, and 10 normal-RI-NOS were identified as fulfilling the inclusion criteria and were analyzed. Considering symptoms before endoscopy, chest pain was more reported in NERD than in other cases (6/18 vs 5/50, P = 0.031). At long-term follow-up of 23 patients (8 NERD, 8 FH, 2 RH, and 5 normal-RI-NOS): 17 were on PPIs and 2 combined alginate, 1 (FH) was on benzodiazepine + anticholinergic, 1 (normal-RI-NOS) on citalopram, and 3 had no therapy. A complete symptom-resolution was observed in 5/8 NERD, in 2/8 FH, and in 2/5 normal-RI-NOS. FH may be the most common pediatric NEEP. At long-term follow-up, there was a trend toward a more frequent complete symptom resolution with PPI-therapy in NERD patients while other groups did not benefit from extended acid-suppressive-treatment.

Improved diagnostic yield of symptom association probability involving only cough for gastroesophageal reflux-induced chronic cough.

Use of symptom association probability (SAP) is recommended for identifying gastroesophageal reflux-induced chronic cough (GERC). This study aimed to compare the diagnostic yield of SAPs involving only cough (C-SAP) or total symptoms (T-SAP) for GERC identification. Patients with both chronic cough and other reflux-related symptoms underwent multichannel intraluminal impedance-pH monitoring (MII-pH) between January 2017 and May 2021. C-SAP and T-SAP were calculated based on the patient-reported symptoms. GERC was definitively diagnosed by the favorable response to anti-reflux therapy. The diagnostic yield of C-SAP in identifying GERC was evaluated by receiver operating characteristic curve analysis and compared with that of T-SAP. MII-pH was performed in 105 patients with chronic cough, and GERC was confirmed in 65 (61.9%), including 27 (41.5%) cases of acid GERC and 38 (58.5%) cases of non-acid GERC. The positive rates of C-SAP and T-SAP were comparable (34.3% vs. 23.8%, P>0.05), but C-SAP exhibited a higher sensitivity (53.85% vs. 33.85%, χ2=8.117, P=0.004) and similar high specificities (97.5% vs. 92.5%, P>0.05) compared with T-SAP for GERC identification. C-SAP was also more sensitive for recognition of acid GERC (51.85% vs. 33.33%, χ2=7.386, P=0.007) and non-acid GERC (65.79% vs. 39.47%, χ2=14.617, P<0.001). More GERC patients with positive C-SAP needed intensified anti-reflux therapy for cough resolution when compared with those with negative C-SAP (82.9% vs. 46.7%, χ2=9.449, P=0.002). C-SAP was superior to T-SAP for the identification of GERC and may improve the diagnostic yield of GERC.

Clinical trial: a controlled trial of baclofen add-on therapy in PPI-refractory gastro-oesophageal reflux symptoms.

Proton pump inhibitors (PPI) have no effect on non-acid reflux events which can continue to provoke gastro-oesophageal reflux disease (GERD) symptoms. Baclofen, a γ-aminobutyric acid agonist, can decrease non-acid reflux but its symptomatic benefit in refractory GERD symptoms is understudied. To assess the efficacy of baclofen 10mg t.i.d. vs placebo as add-on therapy in PPI-refractory GERD symptoms, in a randomised, double-blind, placebo-controlled study. Patients with persisting typical GERD symptoms on b.i.d. PPI therapy were randomised to 4 weeks of baclofen 10mg or placebo t.i.d. Before and after treatment, patients underwent 24 h impedance-pH monitoring on-PPI. Throughout the study, patients filled out ReQuest diaries. Data were analysed using mixed models. About 60 patients were included (age 47.5 years [range 19-73], 41f/19 m), 31 patients were randomised to baclofen. One patient withdrew consent and five in the baclofen group stopped treatment due to side effects. There was a trend towards a better response for general wellbeing in the baclofen-treated group compared to placebo (p= 0.06). When subdividing patients according to symptom association probability (SAP), only the SAP+ (n= 25) group improved significantly with baclofen (pcorr = 0.02), and worsened with placebo (pcorr = 0.008). The total number of reflux events decreased over time (p= 0.01), mainly due to the baclofen condition (pcorr = 0.1). The number of reflux events with a high proximal extent dropped significantly after baclofen (pcorr = 0.009), but not placebo. Baclofen decreases several reflux parameters in PPI refractory GERD symptoms, but pH-impedance monitoring is necessary before treatment as only SAP+ patients experience clinical benefit after 4 weeks.

Symptom Association for Gastroesophageal Reflux Disease by pH Monitoring After Peroral Endoscopic Myotomy.

There are limited data correlating symptoms with reflux episodes during pH studies after peroral endoscopic myotomy. Consecutive patients who underwent POEM followed up ≥6 months later by 48-hour ambulatory wireless pH testing off antisecretory therapy were identified. Reflux symptom association was defined as symptom association probability &gt;95%. The most frequent symptoms of heartburn (47.2%), cough (45.1%), and chest pain (39.6%) were associated with a positive reflux symptom association (symptom association probability &gt;95%) in 20.9%, 17.1%, and 19.4%, respectively. There is poor correlation between reported symptoms and esophageal acid exposure during pH testing after POEM.

Symptom Scores and pH-Impedance: Secondary Analysis of a Randomized Controlled Trial in Infants Treated for Gastroesophageal Reflux.

BACKGROUND AND AIMS:To evaluate and compare gastro-esophageal reflux (GER) symptom scores with pH-impedance and test the effects of acid-suppressive medications with or without feeding modifications on pH-impedance in high-risk infants.METHODS:Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R) and 24-hour pH-impedance data were analyzed from 94 infants evaluated in a tertiary care setting for GER disease. Longitudinal data from 40 infants that received randomized GER therapy (proton pump inhibitor [PPI] with or without feeding modifications) for 4 weeks followed by 1-week washout were analyzed. Relationships between I-GERQ-R and pH-impedance metrics (acid reflux index, acid and bolus GER events, distal baseline impedance, and symptoms) were examined and effects of treatments compared.RESULTS:(A) Correlations between I-GERQ-R and pH-impedance metrics were weak. (B) I-GERQ-R sensitivity, specificity, and positive predictive values were suboptimal when correlated with pH-impedance metrics. I-GERQ-R negative predictive value (NPV) was high for acid symptom–association probability (NPV = 84%) and distal baseline impedence (NPV = 86%) thresholds. (C) PPI with feeding modifications (vs PPI alone) did not alter pH-impedance metrics or symptom scores (P > .05); however, bolus clearance metrics worsened for both treatment groups (P < .05).CONCLUSIONS:In high-risk infants (1) I-GERQ-R may be a helpful clinical screening tool to exclude acid-GER disease diagnosis and minimize unnecessary acid-suppressive treatment, but further testing is needed for diagnosis. (2) Acid-suppressive therapy with feeding modifications has no effect on symptom scores or pH-impedance metrics. Clearance of refluxate worsened despite PPI therapy, which may signal development of pharyngoesophageal dysmotility and persistence of symptoms. (3) Placebo-controlled trials are needed in high-risk infants with objective pH-impedance criteria to determine efficacy, safety, and underlying mechanisms. Clinicaltrials.gov ID: NCT02486263.

Is belching increasing after bariatric bypass surgery in the long term period?

Gastric bypass surgery effectively treats obesity; however, its association with belching, which occurs in other bariatric surgeries, remains unclear. Hence, we aimed to evaluate belching occurrence after gastric bypass surgery. We enrolled 12 healthy volunteers and 17 patients (12 and 5 underwent Roux-en-Y gastric bypass and mini-gastric bypass surgeries 24 (18-54) months prior, respectively). Gastrointestinal symptoms were assessed. Gastroscopy was performed, followed by the 24-hour pH-impedance analysis. Age and sex were not statistically different between the two groups (P > 0.05). Patients had a significantly higher mean DeMeester score than the healthy controls (9.11 ± 19.40 vs. 6.04 ± 5.60, P = 0.048), but the pathologic acid reflux (DeMeester score > 14) rate was similar in both groups (11.8% vs. 8.3%). Regarding the impedance, symptom-association probability was positive in 11.8% of patients. The patients also had higher alkaline reflux rates (6% vs. 0%); additionally, 50% of them experienced belching based on the questionnaire, and 25% had esophagitis based on gastroscopy. Furthermore, patients had a significantly higher number of gas reflux (123.24 ± 80 vs. 37.2 ± 21.5, P = 0.001) and supragastric/ gastric belches (182 ± 64/228 ± 66.69 vs. 25.08 ± 15.20/12.17 ± 17.65, P = 0.001). Supragastric belching was more frequent than gastric belching in the controls, whereas gastric belching was more frequent in the patients. Belching increases after gastric bypass surgery in a long-term period. Gastric belching was more frequent than supragastric belching in these patients.

788 VARIABLE GEOGRAPHICAL DIFFERENCES OF AMBULATORY ESOPHAGEAL REFLUX MONITORING IN MEXICO

Abstract Ambulatory esophageal reflux monitoring (AEpH) is useful in evaluating persistent or refractory esophageal symptoms despite adequate pharmacologic and/or surgical therapy. There is limited information whether there are geographical or regional differences in the diagnostic outcome of this test. Aim Characterize the diagnostic outcome of AEpH in a diverse population of Mexico. Analyze whether there is regional geographical diagnostic variability. Methods Data was collected from four major referral centers representing diverse geographical areas of Mexico: Mexico City-Central (two centers, years 2016-2020), Veracruz-South (years 2015-2020) and Monterrey-North (years 2013-2020). Consecutive patients undergoing AEpH with persistent GERD symptoms despite PPI therapy and negative upper endoscopy (no erosive disease &amp;gt;C or D LA classification) were entered into a data base and analyzed. Patients were classified as: NERD (acid exposure time (AET &amp;gt; 6.0%); hypersensitive esophagus (normal AET and positive symptom index (SI) or positive symptom association probability [SAP]); functional heartburn (NL AET, neg SI/SAP). Statistics: ANOVA, Chi-square and descriptive methods were used to compare variables among groups. Results 969 cases met inclusion criteria: 311 (32.1%) Central, 430 (44.3%) South, and 228 (23.5%) North. The results are summarized in the table. There were more women 618(63.8%) than men 351(36.2%); p &amp;lt; 0.001 with a mean age 47.7 ± 14.3. Patients were older in Central-Mexico 49.3 ± 13.6 years vs South 47.5 ± 15 and North 46.1 ± 13.6; p = 0.033. Functional heartburn was the most common diagnosis overall and more prevalent in Central-Mexico 171(55%) vs North 97(42.5%) and South 160(37.2%); p &amp;lt; 0.001. NERD was more predominant in the South 171(39.8%) vs North 72(31.6%) and Central-Mexico 98(31.5%); p = 0.029. Hypersensitive esophagus was more frequent in the North 59(25.9%) vs South 99(23%), and Central 42(13.5%); p &amp;lt; 0.001. Conclusion This is the first large data base study to evaluate the outcome of ambulatory esophageal reflux pH testing in Mexico. Our findings indicate a geographical variability of GERD phenotypes and suggest that further investigations are warranted to determine the causes of this distribution.

Can acid exposure time replace the DeMeester score in the diagnosis of gastroesophageal reflux-induced cough?

Background:The objective of this study was to compare the predictive accuracy of the acid exposure time (AET) with the DeMeester score (DMS) for gastroesophageal reflux–induced cough (GERC).Methods:A total of 277 patients who underwent multichannel intraluminal impedance pH monitoring (MII-pH) were enrolled, and their clinical information and laboratory results were retrospectively analyzed. The diagnostic value of AET for GERC was compared with that of the DMS, symptom association probability (SAP), and symptom index (SI).Results:A total of 236 patients met the inclusion criteria, 150 patients (63.65%) were definitely diagnosed with GERC, including 111(74%) acid GERC and 39 (26%) nonacid GERC. The optimal cutoff value of AET for diagnosing GERC was AET > 4.8%, and its diagnostic value was equal to that of DMS > 14.7 (AUC = 0.827 versus 0.818, p = 0.519) and was superior to that of SAP (AUC = 0.827 versus 0.689, p = 0.000) and SI (AUC = 0.827 versus 0.688, p = 0.000). When using both DMS > 14.7 and AET > 4.8% or either of the two for the diagnosis of GERC, the diagnosis rate was not improved over using DMS > 14.7 alone. The diagnostic value of AET and DMS for acid GERC were both high and equivalent (AUC = 0.925 versus 0.922, p = 0.95). The optimal cutoff value of AET for diagnosing acid GERC was AET > 6.2%.Conclusion:AET and DMS are both equal in discriminating GERC. A GERC diagnosis should be considered when AET > 4.8%, whereas an acid GERC diagnosis should be considered when AET > 6.2%.

Limited Clinical Utility of Lipid-Laden Macrophage Index of Induced Sputum in Predicting Gastroesophageal Reflux-Related Cough.

Gastroesophageal reflux disease (GERD) is a common cause of chronic cough (CC). However, the diagnosis of GERD associated with CC based on 24-hour esophageal pH-monitoring or favorable response to empirical anti-reflux trials is invasive and time-consuming. Lipid-laden macrophages (LLMs) are supposed to be a biomarker for micro-aspiration of gastric content in the respiratory tract. This study was conducted to collect LLMs by the sputum induction technique and observe the relationship among the amount of LLMs, cough severity, parameters of 24-hour esophageal pH-monitoring and therapeutic response. The 24-hour esophageal pH-monitoring and sputum induction were performed on 57 patients with suspected GERD associated with CC. Thirty-four patients were followed up after empirical anti-reflux trials of 8 weeks to record the therapeutic response. Lipid-laden macrophage index (LLMI), a semiquantitative counting of LLMs, showed no significant correlation with the values of 24-hour esophageal pH monitoring at the proximal or remote electrode. No difference in LLMI or DeMeester score, as well as cough symptom association probability, were found between the responders and the non-responders. Reflux symptoms were more common in the responders (50%) compared to the non-responders (6%) (P < 0.05). Our study suggests that LLMI shows limited utility in clinically diagnosing GERD associated with CC as an underlying etiology or in predicting response to anti-reflux therapy. Anti-reflux therapy is more effective for CC patients with reflux symptoms than for those without.

S0437 Impact of Incorporating Mean Nocturnal Basal Impedance as a Supplemental Metric to Acid Exposure Time in Patients With Esophageal Symptoms

INTRODUCTION: While acid exposure time (AET) predicts response to anti-reflux treatment and is the most validated parameter of pH monitoring, it is limited by daily variations and does not directly evaluate tissue damage. However, Distal mean nocturnal basal impedance (dMNBI) does measure gastroesophageal reflux (GER) related damage (increased mucosal permeability). dMNBI is validated to assess response to anti-reflux treatment and has become a valuable supplemental metric to AET. We report the impact of combining AET with dMNBI for classifications of gastroesophageal reflux disorder (GERD) including pathologic GER, esophageal hypersensitivity (EH), and functional symptoms (FS). METHODS: Patients who underwent pH-impedance monitoring off of proton pump inhibitor (PPI) therapy for refractory GERD at our center from Oct 2013 to March 2020 were included. Those with achalasia, esophagogastric junction outflow obstruction, scleroderma, and those evaluated for cough were excluded. dMNBI was calculated as the average impedance of three uninterrupted 10-minute intervals collected at night 3 cm proximal to the GE junction. dMNBI < 2.29 or AET >6% were considered abnormal. EH was defined as AET< 6% and/or dMNBI< 2.29kOhm with a symptom association probability (SAP) > 95%. FS was defined as AET< 6% and/or dMNBI< 2.29 kOhm and SAP < 95%. RESULTS: A total of 267 patients underwent pH-impedance monitoring off of PPI therapy. 206 patients were included in the analysis. 5 patients completed less than 12 hours of the study and 46 met exclusion criteria. The mean age was 50 (±15) years, 150 (73%) were females, 162 (79%) were Caucasian, 93 (46%) were current or former smokers, and mean BMI was 31 (±7). The AET was abnormal in 53 (26%), intermediate in 19 (9%), and normal in the remainder. With AET alone, 26% were classified as pathological GER, 23% were EH, 32% were FS, and 19% were undetermined (Figure 1). Combined AET and dMNBI based classification resulted in pathological GER in 46%, EH in 13%, FH 23%, and undetermined in 17% (Figure 2). This difference in classification was statistically significant (P < 0.0001). CONCLUSION: Using dMNBI in conjunction with AET identifies a significant proportion of patients with GERD and decreases patients classified with FS. This has an important clinical impact as GERD patients receive different treatment than patients with functional symptoms. Enhancing AET with dMNBI facilitates more accurate diagnoses and aids in the future management of patients with esophageal conditions.Figure 1.: Outcome classification by acid exposure time (AET) alone.Figure 2.: Outcome classification by combined acid exposure time (AET) and distal mean nocturnal basal impedance (dMNBI).

Gastroesophageal reflux disease in pediatric esophageal atresia: Assessment of clinical symptoms and pH-impedance data.

BACKGROUNDEsophageal atresia (EA) is the most common congenital anomaly of the gastrointestinal tract. Gastroesophageal reflux disease (GERD) is a frequent and lifelong problem in these patients. GERD can be asymptomatic and the incidence of esophageal gastric and intestinal metaplasia (Barrett’s esophagus) is increased in adults with EA compared with the general population. Timely and accurate diagnosis of GERD is important to reduce long-term problems and this may be achieved by pH-impedance testing.AIMTo assess symptoms and pH-impedance data in children after EA, in order to identify their specific features of GERD.METHODSThis study was conducted from November 2017 to February 2020 and involved 37 children who had undergone EA via open surgical repair (51.35% boys, 48.65% girls; age range: 1-14 years, median: 4.99 years). GERD diagnosis was made based on multichannel intraluminal impedance/pH study and two groups were established: EA without GERD, n = 17; EA with GERD, n = 20. A control group was established with 66 children with proven GERD (68.18% boys, 31.82% girls; median age: 7.21 years), composed of a nonerosive reflux disease (referred to as NERD) group (n = 41) and a reflux esophagitis group (n = 25). Upper gastrointestinal endoscopy with a mucosal esophageal biopsy was performed on all patients.RESULTSThe most frequently observed symptom in EA patients with GERD and without GERD was cough (70% and 76.5% respectively). The number of patients with positive symptom association probability in the EA groups was significantly larger in the EA without GERD group (P = 0.03). In the control reflux esophagitis group, prevalence of gastrointestinal symptoms was significantly higher than in the NERD group (P = 0.017). For both EA groups, there was strong correlation with index of proximal events (IPE) and total proximal events (EA with GERD: 0.96, P < 0.001; EA without GERD: 0.97, P < 0.001) but level of IPE was significantly lower than in GERD patients without any surgical treatment (P < 0.001). Data on distal mean nocturnal baseline impedance were significantly different between the EA with GERD group (P < 0.001) and the two control groups but not between EA without GERD and the two control groups.CONCLUSIONMean nocturnal baseline impedance may have diagnostic value for GERD in EA children after open surgical repair. IPE might be an additional parameter of pH-impedance monitoring.

The Role of Symptom Association Analysis in Gastroesophageal Reflux Testing.

Gastroesophageal reflux disease is characterized by the reflux of gastric contents into the esophagus with an estimated worldwide prevalence of 8%-33%. The current paradigm in gastroesophageal reflux disease diagnosis relies on recognition of symptoms and/or the presence of mucosal disease at the time of esophagogastroduodenoscopy. Recognition of symptoms, however, can arise with challenges, particularly when patients complain of less typical symptoms. Since first reported in 1969 by Spencer et al., the application of prolonged intraesophageal pH monitoring to identify pathologic reflux has evolved considerably. Utility of pH monitoring aims to investigate the degree of acid burden and frequency of reflux episode, and the relationship between symptoms and acid reflux events. This relationship is represented by either the Symptom Index, Symptom Sensitivity Index, Symptom Association Probability, or Ghillebert Probability Estimate. This article reviews symptom-association analysis during esophageal reflux testing, covering the literature on current methods of reflux testing, interpretation of symptom association, and practical issues that can arise during symptom analysis.

Laryngeal signs and pH-multichannel intraluminal impedance in infants and children: The missing ring: LPR and MII-pH in children

Objectiveto investigate the reliability of laryngeal reflux finding score (RFS) and symptom index (RSI) in assessing gastroesophageal reflux (GER) in children and infants. Methodspatients with laryngeal or respiratory symptoms, who underwent laryngoscopy and esophageal pH-impedance (MII-pH) were recruited. RSI and RFS were correlated to MII-pH results. A RSI>13, RFS>7, acid exposure index>7%, total reflux episodes>100/24 h in infants or>70/24 h in children, or a positive symptom index or association probability, were considered pathological. Analysis considering age (</>12 months) was performed. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of the laryngeal scores were calculated. Results197 children (median 53 months, 61 infants) were enrolled. MII-pH was pathological in 5/10 patients with RFS>7, and in 17/31 with RSI>13. RFS>7 had 3.9% sensitivity, 93% specificity, a PPV of 50 and a NPV of 34 in predicting GER disease. RFS was inversely associated to weakly acidic and proximal GER. RSI>13 had 13% sensitivity, 83% specificity, and a PPV and NPV similar to RFS. RSI was significantly associated with the number of acid reflux episodes, and, in infants, with bolus exposure index. ConclusionsRSI and RFS aren't accurate in predicting GER in infants and children. Acid reflux relates to laryngeal symptoms, but neither acid, nor proximal and weakly acidic GER relate to laryngeal alterations.