Proximal Reflux Research Articles

The Role of the Transdiaphragmatic Pressure Gradient (TGP) in the Pathophysiology of Proximal Reflux

IntroductionAn increased transdiaphragmatic pressure gradient (TGP) is a main element for distal gastroesophageal reflux disease (GERD). The role of TGP for proximal reflux is still unclear. This study aims to evaluate the presence, severity, and importance of proximal reflux in relationship to the TGP, comparing healthy volunteers, obese individuals, and patients with chronic obstructive pulmonary disease (COPD). MethodsWe studied 114 individuals comprising 19 healthy lean volunteers, 47 obese individuals (mean body mass index 45 ± 7 kg/m2), and 48 patients with COPD. All patients underwent high-resolution manometry and dual-channel esophageal pH monitoring. Esophageal motility, thoracic pressure (TP), abdominal pressure (AP), TGP, DeMeester score, and % of proximal acid exposure time (pAET) were recorded. ResultsPathologic distal GERD was found in 0, 44, and 57% of the volunteers, obese, and COPD groups, respectively. pAET was similar among groups, only higher for obese individuals GERD + as compared to obese individuals GERD − and COPD GERD −. pAET did not correlate with any parameter in healthy individuals, but it correlated with AP in the obese, TP in the COPD individuals, and TGP and DeMeester score in both groups. When all individuals were analyzed as a total, pAET correlated with AP, TGP, and DeMeester score. DeMeester score was the only independent variable that correlated with pAET. ConclusionsOur results show that (a) TGP is an important mechanism associated with distal esophageal acid exposure and this fact is linked with proximal acid exposure and (b) obesity and COPD both seem to be primary causes for GERD but not directly for proximal reflux.

Pepsin as a biomarker for self-diagnosing reflux associated symptoms in UK and USA individuals

Background: Reflux is a common clinical complaint within the UK and USA population, often causing troublesome symptoms for example, heartburn, regurgitation and hoarseness. These symptoms are commonly associated with gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR). Procedures for diagnosing reflux are at present invasive, time consuming and in some cases not reliable, leading to many individuals seeking a quick and easy non-invasive diagnostic method for self-diagnosis. It has been shown that pepsin detection within a sputum and/or saliva sample is a sensitive, non-invasive diagnostic method for proximal reflux of gastric contents. Using pepsin as a biomarker for reflux led to the development of Peptest, which is a non-invasive, rapid diagnostic procedure used to identify pepsin within a saliva sample. The aim of this study was to show how pepsin can be used as a biomarker for reflux, using Peptest for the self-diagnosis of reflux related symptoms.

Clinical characteristics and esophageal function tests of refractory gastroesophageal reflux disease

Objective: To analyze the clinical characteristics and pathogenesis of refractory gastroesophageal reflux disease(RGERD). Methods: The patients with acid regurgitation, heartburn and extraesophageal symptoms were enrolled in the study from November 2015 to September 2017 at Peking University Third Hospital. All the subjects filled the informed consent.Questionnaire, SCL-90, SAS and SDS scales were recorded. A 24 hour pH-impedance monitoring and esophageal high resonance manometry were carried out. According to the response to proton pump inhibitor(PPI), the patients were divided into RGERD and non-RGERD(NRGERD)groups. The clinical characteristics were compared between these two groups. Logistic regression was used to analyze the risk factors of RGERD. Results: One hundred and nineteen patients were finally enrolled in the study including 61 RGERD (51.3%) and 58 NRGERD patients (48.7%).The body mass index (BMI) and rates of, typical GER symptoms including acid regurgitation in RGERD patients were significantly lower than those in NRGERD patients (P<0.05).While the atypical GER symptoms such as poststernal discomfort or chest pain were more common in RGERD group (P<0.05).RGERD patients presented less acid reflux events and lower proximal segment reflux ratio than NRGERD patients. No obvious differences were found in the manometry metrics between these two groups. The scores of somatization, depression and hostility in RGERD patients by SCL-90 scales were significantly higher than those in NRGERD patients (P<0.05), and depression score was an independent risk factor for RGERD [OR=3.915 (95%CI 1.464-10.466), P =0.007]. Conclusions: RGERD patients present more atypical symptoms and pathological non-acid reflux.Depression is an independent risk factor for RGERD.

Esophageal pH-impedance monitoring of reflux patterns in non-erosive reflux disease, reflux hypersensitivity and functional heartburn

To analyze the differences in reflux patterns in 24-hour esophageal pH-impedance monitoring in patients with non-erosive reflux disease (NERD), reflux hypersensitivity (RH) and functional heartburn (FH) and explore the possible mechanism of symptoms in patients with heartburn and negative endoscopic findings. Seventy-nine patients with heartburn as the main symptoms but negative endoscopic findings, including 35 with NERD, 16 with RH and 28 with FH, were enrolled in this study.All the patients underwent 24-h esophageal pH-impedance monitoring and esophagogastroscopy, and the results were compared among the 3 groups. Acid reflux episode was significantly increased and weakly alkaline reflux episode was significantly decreased in NERD group in comparison with RH group and FH group (P < 0.05).The patients in NERD group showed significantly increased total reflux episode, mixed reflux episode, proximal acid reflux episode, proximal weak acid reflux episode, total proximal reflux episode, percentage of proximal acid reflux, percentage of proximal weak acid reflux, and percentage of total proximal reflux as compared with the other two groups (all P < 0.05).Bolus clear time was significantly prolonged in NERD group compared with that in the other two groups (P < 0.05).Analysis of the reflux acidity showed that the percentages of different reflux episodes differed significantly among the 3 groups (P < 0.05);acid reflux was the main reflux in NERD, while weak acid reflux was the main reflux in RH and FH groups, which had also significantly increased weakly alkaline reflux episodes compared with NERD group. Patients with NERD, RH and FH had different reflux patterns.Acid reflux is predominant in the NERD, while weakly alkaline reflux is significantly increased RH and FH.In patients with normal esophageal acid exposure but without symptoms or without recorded symptoms during esophageal pH-impedance monitoring, analysis of the total reflux episode, mixed reflux episode, proximal acid reflux episode and percentage can help in the differential diagnosis between RH and FH.

Factors of Reflux Episodes With Post-reflux Swallow-induced Peristaltic Wave in Gastroesophageal Reflux Disease.

Background/AimsIt is known that post-reflux swallow-induced peristaltic wave (PSPW) index represents the chemical clearance of the esophagus. However, few studies have explored why some reflux episodes could induce PSPW while others in the same patient could not. The purpose of this study is to investigate the characteristics of reflux episodes which could elicit PSPW.MethodsIn this study, 269 reflux episodes were detected, of which 90 with a PSPW and 179 without a PSPW. Comparisons were made between the characteristics of reflux episodes with a PSPW and without a PSPW. The characteristics were including nadir pH, pH drop, proximal extent (cm, sec), ascending velocity (cm/sec), volume clearance time, acid clearance time, percentage acidic (%), 15 to 60-minute acid burden (seconds), and 15- to 60-minute volume burden (seconds). The characteristics between the 2 groups were compared through performing Wilcoxon signed rank test.ResultsReflux episodes followed by a PSPW were significantly associated with a higher proximal extent than those without a PSPW. After the reflux episodes, higher volume clearance time and larger volume burden were more likely to trigger a PSPW. However, there were no significant differences between the 2 groups in nadir pH, pH drop, ascending velocity, acid clearance time, percentage acidic, or acid burden.ConclusionsThe role of acid seems to be less important in a reflux episode inducing a PSPW. Proximal reflux episodes are more likely to induce a PSPW. The depression of volume clearance may also be an important factor in eliciting a PSPW.

Proximal reflux: biochemical mediators, markers, therapeutic targets, and clinical correlations.

Airway reflux is implicated in the pathophysiology of a wide range of adult and pediatric upper and lower airway diseases. However, the diagnosis of proximal reflux-associated disease remains challenging due to evolving clinical criteria and institutional and regional variances in diagnostic practices. Evidence suggests that nonacidic contents of reflux may serve as both pathologic mediators of and biomarkers for reflux in the upper airway. Furthermore, they offer potential pharmaceutical and surgical intervention targets and are the focus of novel clinical diagnostic tools currently under investigation.

Intermixed Dimethyl-Sulfoxide–Based Nonadhesive Liquid Embolic Agents Delivered Serially via the Same Microcatheter for Cerebral AVM Treatment

Conventional nonadhesive liquid embolic agents currently are the criterion standard for endovascular embolization of cerebral AVMs. However, inadequate distal penetration into the nidus and unstable proximal plug formation are the major limitations of this approach and of the currently available embolic materials. The aim of this study was to evaluate the hypothetic efficacy of combining liquid embolic agents with different properties and viscosities for use in endovascular embolization of cerebral AVMs. From March 2018 to March 2019, sixteen patients with cerebral AVMs (12 women, 4 men; age range, 33-61 years) underwent endovascular embolization with combined liquid embolic agents delivered serially via a single microcatheter. The procedure consists of initial embolization with PHIL 30%, followed by Menox 18 through the same microcatheter. According to the Spetzler-Martin scale, 11 (68.75%) AVMs were grades I-II, 4 (25%) were grade III, and 1 (6.25%) was grade IV. Angiographic, technical, and clinical outcomes were analyzed independently. Combined PHIL and Menox embolization through the same microcatheter via 21 pedicles was performed in these 16 patients. Once the length of the reflux reached approximately 2 cm, PHIL 30% was switched to Menox 18. Antegrade flow and distal penetration of the serially applied liquid embolic agents were observed in all 16 cases. The ability to completely control the flow of the materials and avoid any dangerous proximal reflux was noted in all performed embolizations. The estimated average size reduction of the treated AVMs was 85%, ranging from 50% to 100%. Complete embolization was achieved in 10/16 or 62.5% of the cases. There was no procedure-related complication during or after the embolization. No mortality or postprocedural clinical worsening was seen. Clinical success and complete obliteration were confirmed with at least 1 follow-up angiography in 10/16 patients. Serial delivery of nonadhesive liquid embolic agents via the same microcatheter was safe and effective in our study and may be a potential technique for routine AVM treatment. However, further investigations are required to validate the safety and the efficacy of the method.

Rumination Syndrome in Children Presenting With Refractory Gastroesophageal Reflux Symptoms.

Up to 40% of children presenting with reflux symptoms do not respond to standard medical interventions. In adults, 20% of patients presenting with Proton Pump Inhibitors refractory Gastro-Esophageal Reflux Disease (GERD) have rumination syndrome. The management of GERD and rumination differ significantly. Our study aimed to identify rumination syndrome amongst children presenting with persistent GERD symptoms based on a distinct pattern on impedance-pH monitoring. The parameters of impedance-pH monitoring were compared between children with rumination syndrome (n = 12), diagnosed on high-resolution manometry impedance (HRM/Z), children with GERD (n = 18), children with an alternative diagnosis (non-GERD, n = 12) and children negative for rumination based on HRM/Z (n = 14). The parameters that distinguish the rumination group were identified and incorporated into a scoring system, which was blindly applied on a separate group of children with refractory GERD (n = 18) to define its sensitivity and specificity. Rumination syndrome presents in 44% of children with refractory GERD. Children with rumination syndrome present with a large number of proximal reflux episodes (>57.5 episodes/24 hours); a high frequency of nonacid reflux events in the postprandial period (>2/hour); and a highly positive symptom-reflux association analysis (SAP ≥ 95%). A score of ≥2 out of the 3 points distinguishes children with rumination syndrome with 75% sensitivity and 80% specificity. Children with rumination syndrome have a distinct pattern of impedance-pH monitoring and can be distinguished amongst children presenting with refractory GERD. Applying a simple scoring system during impedance-pH analysis could lead to early diagnosis of children with rumination syndrome.

A study of proximal esophageal baseline impedance in identifying and predicting laryngopharyngeal reflux.

Laryngopharyngeal reflux (LPR) is caused by the reflux of gastric contents beyond the esophagus into the larynx and pharynx. However, upper esophageal sphincter (UES) motility and proximal esophagus reflux parameters are poorly studied. This study aims to explore the characteristics of UES motility and reflux parameter among LPR patients. Patients with laryngopharyngeal symptoms only (L), patients with laryngopharyngeal symptoms and typical esophageal symptoms (L+E), patients with typical esophageal symptoms only (E), and healthy controls (H) were retrospectively included. Physiological profiles were studied and compared among groups using both high-resolution manometry and pH-impedance monitoring, including UES basal pressure, residual pressure, relaxation duration time, recovery time, the time to nadir pressure, UES length, proximal contractile integral, and proximal mean nocturnal baseline impedance (MNBI). Patients' symptom outcomes were also analyzed. A total of 242 patients were included. Proximal MNBI was significantly lower in patients with both laryngopharyngeal and esophageal symptoms (17cm above low esophageal sphincter [LES]: L vs L+E vs E vs H=3689.7 vs 2500.0 vs 3073.0 vs 3996.0; 15cm above LES: L vs L+E vs E vs H=3155.9 vs 2553.4 vs 3198.9 vs 2985.2; P<0.001). Patients responded to proton pump inhibitor treatment also had lower proximal MNBI than those who did not (17cm above LES: 1834.0 vs 3500.0; 15cm above LES: 1946.5 vs 3432.6; P<0.001). Decreased proximal MNBI can not only identify LPR patients but also predict patients' symptom outcomes.

Gastroesophageal reflux in laryngopharyngeal reflux patients: Clinical features and therapeutic response.

To investigate the clinical features and the therapeutic response of laryngopharyngeal reflux (LPR) patients with or without gastroesophageal reflux disease (GERD). Patients with LPR symptoms were enrolled from three European Hospitals. The diagnosis of LPR and GERD was made through impedance-pH monitoring (MII-pH). A gastrointestinal endoscopy was realized in patients with digestive complaints or ≥60 years old. The 3- to 6-month treatment was based on the association of diet, pantoprazole, alginate, and magaldrate regarding the MII-pH characteristics. Reflux Symptom Score (RSS) and Reflux Sign Assessment (RSA) were used to evaluate the clinical evolution throughout treatment. The gastrointestinal endoscopy findings, clinical features, and therapeutic response were compared between patients with LPR and GERD (LPR/GERD) and patients with LPR. One hundred and eleven LPR patients were included, 54 being LPR/GERD. LPR/GERD patients had a higher number of proximal reflux episodes compared with LPR patients. The prevalence of esophagitis, hernia hiatal, and lower esophageal sphincter insufficiency did not differ between groups. The presence of GERD was strongly associated with acid LPR. Patients without GERD had a higher proportion of nonacid and mixed LPR compared with LPR/GERD patients. The pre- to posttreatment evolutions of RSS and RSA were quite similar in both groups, with the exception of the 3- to 6-month improvement of digestive symptoms, which was better in LPR/GERD group. The therapeutic success rates were 79.6% and 77.2% in GERD/LPR and LPR group, respectively. GERD is predictive of acid LPR. The clinical evolution and the therapeutic response rates were quite similar in both groups. 4 Laryngoscope, 130: E479-E489, 2020.

Does the Reflux Symptom Index Predict Increased Pharyngeal Events on HEMII-pH Testing and Correlate with General Quality of Life?

To determine the ability of the reflux symptom index (RSI) to predict objective impedance and pH-probe testing, and to examine the relationship between disease-specific and general health status in patients diagnosed with laryngopharyngeal reflux (LPR). Adults presenting to a tertiary care academic center with a primary voice complaint completed the RSI and the Patient-Reported Outcomes Measurement Information System 10-item global health instrument (PROMIS). An RSI score ≥13 was considered abnormal. Objective testing for LPR was performed using hypopharyngeal-esophageal multichannel intraluminal impedance catheter with dual pH (HEMII-pH) testing; a positive test was defined as more than one pharyngeal impedance events over 24 hours. Spearman rho analyses were applied, and the sensitivity and specificity of the RSI to detect HEMII-pH findings were determined. One hundred four patients underwent HEMII-pH testing. Mean scores were 16.7 (95%CI 15.1-18.3) for RSI. Sixty-three (60.6%) patients were diagnosed with LPR by HEMII-pH testing. RSI scores were moderately correlated with PROMIS physical (Spearman rho 0.43, P < 0.0001), social (Spearman rho 0.33, P < 0.0001) and mental health (Spearman rho 0.33, P < 0.0001) scores. The RSI has a sensitivity and specificity of 66.7% and 31.7%, respectively, for detecting pharyngeal events on HEMII-pH testing. There is moderate sensitivity and lack of specificity of the RSI for detecting increased pharyngeal reflux events. Reflux-specific and general health status instruments are correlated. Further investigation could assess the diagnostic ability of RSI compared proximal reflux events on HEMII-pH, as well as whether health status instruments can be used to detect clinically meaningful change in the LPR population.

Saphenous reflux patterns in C2 patients: A record of 1196 ultrasound reports.

To describe saphenous reflux patterns in patients classified as CEAP C2 by analysis of 2027 vascular ultrasound examination reports. A total of 2027 venous mapping studies were reviewed and 1196 patients classified as CEAP C2 were selected. Patients were classified according to patterns of reflux for the great saphenous vein and for the small saphenous vein, and rates of great saphenous vein and small saphenous vein reflux were analyzed for both sexes. The overall prevalence of saphenous vein reflux was 45%. Males had significantly higher great saphenous vein reflux prevalence than females (p < 0.001). The most common great saphenous vein reflux pattern in females was segmental reflux and the most common pattern in males was proximal reflux. Saphenous vein reflux is common in C2 patients and is more frequent in males. Standardization of classifications of reflux patterns is very important for correct management of the disease.

Embolization of a Complex Facial Arteriovenous Malformation, Balloon-Assisted Flow Arrest, and Controlled n-BCA Injection with Dextrose Push Technique: 2-Dimensional Operative Video.

N-butyl cyanoacrylate glue (n-BCA, Cerenovus, Irvine, California) is commonly used to treat arteriovenous malformation (AVM). Even though Onyx (ethylene vinyl alcohol, Medtronic, Dublin, Ireland) presents more controlled injection, n-BCA is colorless, thus preferable for treatment of superficial facial malformations. N-BCA injection into AVM can result in premature distal migration or early precipitation and reflux into the feeder vessels. Here we describe a trans-arterial balloon assisted technique embolization of a complex facial AVM with n-BCA. A 22-yr-old female with chronic oral/gum bleeding presented with a complex facial AVM. She underwent selective transarterial n-BCA balloon assisted treatment with dextrose push. Informed written consent was obtained. A Scepter dual lumen balloon (MicroVention, Aliso Viejo, California) and a Prowler microcatheter (Cerenovus) were introduced via a 6-French Envoy guide catheter (Cerenovus) selectively into the AVM feeder. The balloon was positioned 3 cm proximal to the Prowler microcatheter tip and fully inflated to create flow arrest. Diluted 25% concentration of n-BCA in Ethiodol Oil was injected through the Prowler microcatheter. The distal migration of the n-BCA was modulated with simultaneous injection of Dextrose 5% in water via the Scepter balloon. This resulted in a controlled glue injection without early distal glue migration (because of the flow arrest) nor early proximal glue precipitation or reflux (because of the dextrose infusion), obtaining complete cure of the complex facial AVM. Glue embolization with flow arrest and dextrose push allows well controlled injection, and it represents a valid option also for high flow vascular lesions.

GER characteristics after fundoplication in children with aerodigestive disorders

PurposeThe purpose of this study was to determine GER characteristics after Nissen fundoplication in children with aerodigestive disorders using pH-impedance technology. MethodsIn this cross-sectional study, the institutional database of Cincinnati Children's Hospital Medical Center was reviewed to identify patients ages below 21 years who had a Nissen fundoplication and underwent esophageal pH-impedance (pH-MII) monitoring over a nine-year period. All reflux-related metrics were modeled as a Poisson random variable as a function of time since fundoplication. ResultsA total of 242 patients were included in the study. The range for time since surgery was 1–192 months. Median total reflux events were 8.5 episodes per 24 h, median acidic reflux events were 0, and median proximal reflux event was 2. There was no significant trend towards increasing reflux episodes over time. ConclusionsChildren had a low number of reflux events after a fundoplication, as measured by pH-impedance, and there was no statistically significant increase observed in the number of reflux events over time. Despite most patients having a functional fundoplication with minimal reflux events throughout the entire age range, up to 58% of our cohort was still on a proton pump inhibitor.

Patients with acid, high-fat and low-protein diet have higher laryngopharyngeal reflux episodes at the impedance-pH monitoring.

To assess the impact of diet on the occurrence of proximal reflux episodes at the multichannel intraluminal impedance-pH monitoring (MII-pH) in patients with laryngopharyngeal reflux (LPR). Patients with LPR symptoms and findings were recruited from three European hospitals. The LPR diagnostic was confirmed through MII-pH and patients were benefited from gastrointestinal (GI) endoscopy. Regarding the types of reflux at the MII-pH (acid, nonacid, mixed), patients received a 3month-therapy based on the association of alkaline, low-fat and high-protein diet, proton pump inhibitors, alginate or magaldrate. Reflux symptom score (RSS) and reflux sign assessment (RSA) were used to evaluate laryngeal and extra-laryngeal symptoms and findings from pretreatment to posttreatment. The Global Refluxogenic Score (GRES) was used to assess the refluxogenic potential of the diet of the patients at baseline and posttreatment. The relationship between GRES severity; the MII-pH findings; GI endoscopy; and the therapeutic response was explored through multiple linear regression. Eighty-five LPR patients were included. The mean GRES significantly improved from pretreatment (50.7 ± 23.8) to posttreatment (27.3 ± 23.2; P = 0.001). Similarly, RSS and RSA significantly improved from baseline to posttreatment. The baseline GRES was significantly associated with the occurrence of proximal reflux episodes at the MII-pH (P = 0.001). Trends were found regarding the association between GRES and the occurrence of esophagitis (P = 0.06) and between hiatal hernia and DeMeester score (P = 0.06). There was a significant and strong association between the concomitant respect of diet and medication and the improvement of RSS (P = 0.001). The consumption of high-fat, low-protein, high-sugar, acid foods, and beverages is associated with a higher number of proximal reflux episodes at the MII-pH, according to the global refluxogenic score of LPR patients.

Reflux characteristics in patients with gastroesophageal reflux-related chronic cough complicated by laryngopharyngeal reflux.

This study aimed to investigate the reflux characteristics in patients with gastroesophageal reflux-related chronic cough (GERC) complicated by laryngopharyngeal reflux (LPR). Patients with chronic cough were recruited. Reflux symptom index (RSI) scoring, cough symptom scoring, assessment of capsaicin cough sensitivity, and multichannel intraluminal impedance and pH monitoring (MII-pH) were performed. RSI score in GERC patients was significantly higher than that in patients with atopic cough (AC), cough variant asthma, eosinophilic bronchitis (EB), and upper airway cough syndrome (UACS) (P<0.05). The RSI score in non-acid GERC patients was significantly higher than that in acid GERC patients (P=0.003). The cut-off value of the RSI score was defined as 19 during diagnosis of non-acid GERC. In the RSI ≥19 group, there was more proximal reflux and more significant gas and non-acid reflux, and the efficacy of a combined use of baclofen or gabapentin was better than that of the RSI <19 group (P<0.05). The efficacy of proton pump inhibitor (PPI) at a routine dosage together with prokinetic agents in the RSI <19 group was better than that in the RSI ≥19 group (P=0.009). LPR overlaps with GERC in part. GERC patients with higher RSI scores may present more proximal reflux, non-acid reflux, and gas reflux, and get better efficacy with neuromodulators (gabapentin or baclofen) used as an add-on therapy.

364 Shorter Esophageal Length Is Associated With Increased Proximal Reflux and Symptom Severity in Patients Presenting With Laryngopharyngeal Reflux (LPR) Symptoms

INTRODUCTION: Laryngopharyngeal reflux (LPR) is a heterogeneous condition with various underlying pathologies. The effect of esophageal anatomy on LPR is unclear. Shorter distance between lower esophageal sphincter (LES) and upper esophageal sphincter (UES) may allow refluxate to more easily reach the pharynx. We aimed to examine the effect of esophageal length on reflux parameters and symptoms. METHODS: 115 consecutive patients (64% female, mean age 53.9 yrs) with suspected LPR referred for high-resolution manometry (HRM) and combined hypopharyngeal-esophageal multichannel intraluminal impedance-pH testing (HEMII-pH) at a tertiary center in 3/2018-5/2019 were enrolled. Validated symptom surveys were prospectively collected at time of testing, including Reflux Symptom Index (RSI) and 12-item short-form health survey (SF-12) for health-related quality of life (HRQOL). Esophageal length was measured from the distal margin of UES to the proximal margin of LES on HRM. Univariate analyses were performed with Pearson correlation or Student’s t-test. Generalized linear regression was used for multivariate analysis. RESULTS: Mean esophageal length on HRM was 20.4 cm (SD = 2.2). Esophageal length was significantly shorter among patients with a hiatal hernia ≥2 cm (19.2 cm vs 20.6 cm, P = 0.01), but did not correlate with any primary motility disorder per Chicago classification v3.0. Shorter esophageal length was significantly associated with higher acid exposure time and proximal reflux events on impedance, with a trend toward more total reflux events (Table 1). Esophageal length was also shorter among patients with pharyngeal reflux events on HEMII-pH compared to those without (20.0 cm vs 20.9 cm, P = 0.04). Even after controlling for hiatal hernia size, esophageal length remained independently predictive of reflux severity and pharyngeal reflux events. There was a correlation between shorter esophageal length and more severe symptoms on the heartburn/chest pain/indigestion subscore of RSI, but not total RSI or throat symptom subscores (Table 2). Shorter esophageal length was associated with lower physical health scores on SF-12 for HRQOL (Figure 1). CONCLUSION: Shorter esophageal length is independently associated with increased reflux severity, proximal reflux, and pharyngeal reflux, even after controlling for hiatal hernia size. It also correlates with more severe typical reflux symptoms and physical HRQOL. Decreased esophageal length may play a role in the pathophysiology of reflux in patients with LPR symptoms.

Gastroesophageal reflux disease and chronic cough: A possible mechanism elucidated by ambulatory pH-impedance-pressure monitoring.

BackgroundThe pathophysiological mechanism(s) of gastroesophageal reflux disease (GERD)‐related chronic cough (CC) is unclear. We aimed to determine the mechanism of reflux‐induced cough by synchronous monitoring of reflux episodes, esophageal motility, and cough.MethodsPatients with GERD were prospectively enrolled and classified into GERD with CC (GERD‐CC) and without CC (GERD) groups. Twenty‐four‐hour ambulatory pH‐impedance‐pressure monitoring was performed; the reflux patterns, esophageal motility during prolonged exposure to acid and characteristics of reflux episodes that induced coughing paroxysms were analyzed.Key ResultsThirty‐one patients with GERD‐CC and 47 with GERD were enrolled; all of whose monitoring results fulfilled the criteria for diagnosis of GERD. Patients with GERD‐CC had higher reflux symptom scores, longer exposure to acid, higher DeMeester scores, and more frequent reflux episodes, proximal extent reflux detected by impedance, and higher percentage of strongly acidic reflux than patients in the GERD group (all P < .05). Of 63 reflux‐cough episodes identified in the GERD‐CC group, 74.6% of distal reflux and 67.0% of proximal reflux episodes were acidic. More patients had low pan‐esophageal pressure in primary peristalsis (48.5% vs 11.8%, P = .000) and synchronous contraction in secondary peristalsis during prolonged exposure to acid in the GERD‐CC than in the GERD group (63.9% vs 9.1%, P = .000).Conclusions & InferencesProximal acidic reflux and distal reflux‐reflex are jointly associated with reflux‐induced cough in patients with GERD. Low pan‐esophageal pressure in primary peristalsis and synchronous contraction in secondary peristalsis may play important roles in GERD‐associated chronic cough.

Influence of the pH Value of Refluxate and Proximal Extent on Heartburn Perception in Patients with Proton Pump Inhibitor-Refractory Non-Erosive Reflux Disease

Background and Objectives: Weakly acidic reflux has been reported as the major cause of symptom occurrence in patients with proton pump inhibitor (PPI)-refractory non-erosive reflux disease (NERD). This study is aimed at clarifying whether the pH value of weakly acidic reflux affects the induction of symptoms. Methods: We retrospectively evaluated the records of combined multichannel intraluminal impedance and pH monitoring in 57 patients with PPI-refractory NERD. Weakly acidic refluxes were divided into 3 categories based on the pH value of the refluxate: pH 4–5, 5–6, and 6–7. Results: A total of 29 patients were positive in the symptom index. The symptom provocation rate in reflux of pH 4–5 (19%) was much higher than in that of pH 5–6 (11%) and pH 6–7 (12%). In the reflux at pH 4–5, the symptom provocation rate in the proximal reflux was higher than that in the distal reflux (p < 0.05), whereas the reflux at pH 5–6 and pH 6–7 was not significantly different in the symptom provocation rate between the proximal and distal refluxes. Conclusion: Reflux at pH <5 reaching the proximal esophagus was the main factor in the induced symptoms of patients with PPI-refractory NERD.

Correlation of salivary and nasal lavage pepsin with MII-pH testing.

Laryngopharyngeal reflux (LPR) is a common upper airway disease. Salivary pepsin is a proposed marker for LPR; however, the optimal time for collection of specimens for pepsin detection and pepsin's presence in the oral and nasal secretions relative to concurrent multichannel intraluminal impedance-pH (MII-pH) monitoring are unknown. Prospective case-control study with an experimental design. Patients undergoing MII-pH testing for evaluation of LPR and asymptomatic control subjects were selected. Nasal lavage and saliva samples were collected in the clinic prior to MII-pH probe placement. Additional saliva samples were obtained an hour after each meal and upon waking the following morning. Nasal lavage and salivary pepsin were measured by ELISA. Twenty-six patients undergoing MII-pH testing and 13 reflux-free control patients were enrolled. Salivary pepsin was detected in 11 of 26 patients with suspected LPR and 0 of 13 controls. Pepsin was most frequently detected in the specimen provided upon waking at an average concentration of 186.9 ng/mL. A significant correlation was observed between salivary pepsin in waking samples to MII-pH measurements, including reflux bolus duration, and proximal and distal recumbent reflux episodes (P < 0.05). A significant correlation was also observed between salivary pepsin upon waking or sinus lavage and reflux symptom index (P < 0.05). Pepsin in salivary and nasal lavage samples demonstrated an association with MII-pH-documented LPR. Pepsin detection was most frequent in morning samples, supporting use of morning salivary pepsin levels as a potential noninvasive technique for LPR diagnosis. 2 Laryngoscope, 130:961-966, 2020.