Hypopharyngeal Multichannel Intraluminal Impedance Research Articles

Reflux-related Extraesophageal Symptoms Until Proven Otherwise: A Direct Measurement of Abnormal Proximal Exposure Based on Hypopharyngeal Multichannel Intraluminal Impedance as a Reliable Indicator for Successful Treatment Outcomes

Background/AimsThe Lyon Consensus defined parameters based on upper endoscopy and 24-hour combined multichannel intraluminal impedance-pH (MII-pH), that conclusively establish the presence of gastroesophageal reflux disease (GERD). However, the true role of upper endoscopy and MII-pH to evaluate patients with extraesophageal symptoms (EES) has not been well established. Hypopharyngeal MII (HMII), which directly measures laryngopharyngeal reflux (LPR) events, has been utilized to evaluate patients with EES suggestive of LPR.MethodsThis was a retrospective study involving patients with EES for > 12 weeks despite proton pump inhibitor therapy, and had no endoscopic confirmatory evidence for GERD and negative MII-pH. All patients were subsequently referred for further evaluation of EES with “unknown” etiology and underwent laryngoscopy and HMII. Based on HMII, abnormal proximal exposure (APE) was defined as LPR ≥ 1/day and/or full column reflux (reflux 2 cm distal to the upper esophageal sphincter) > 4/day. Patients with APE were offered antireflux surgery (ARS) and the outcome of ARS was objectively assessed using Reflux Symptom Index.ResultsOf 21 patients with EES which was thought to be GERD-unrelated based on endoscopy and MII-pH, 17 patients (81%) had APE. Eight patients with APE who had undergone ARS had significant symptomatic improvement in the Reflux Symptom Index score (19.6 ± 4.9 pre-ARS to 5.8 ± 1.4 post-ARS, P = 0.008).ConclusionsA conventional diagnostic approach using endoscopy and MII-pH may not be sufficient to evaluate patients with EES suggestive of LPR. HMII is essential to evaluate patients with EES, and APE could be a reliable indicator for successful treatment outcomes.

Simultaneous Evaluation of Laryngopharyngeal Reflux and Swallowing Function Using Hypopharyngeal Multichannel Intraluminal Impedance Measurements in Neurologically Impaired Patients.

Background/AimsThis study aims to evaluate the presence of laryngopharyngeal reflux (LPR) and to investigate the use of hypopharyngeal baseline impedance (BI) for assessing swallowing dysfunction and gastroesophageal reflux disease (GERD) using hypopharyngeal multichannel intraluminal impedance and pH (HMII-pH) monitoring in neurologically impaired patients (NIPs).MethodsThe study population in this retrospective study comprised 20 NIPs (mean age, 36.1 ± 15.0 years; age range, 13-64 years) who underwent multichannel intraluminal impedance and pH (MII-pH), HMII-pH, and laryngoscopy using the Hyodo scoring method from December 2016 to April 2019. The MII-pH and HMM-pH parameters were compared in the NIPs, whereas hypopharyngeal BI values were compared between NIPs with ≥ 5 and < 5 in Hyodo scores. Correlations between the hypopharyngeal BI values and the Hyodo score were analyzed using Spearman’s correlation coefficient. A receiver operator characteristic curve was created to determine the optimum cut-off of hypopharyngeal BI value to discriminate SD.ResultsThree NIPs were diagnosed with pathological LPR and GERD by the HMII-pH monitoring. No significant differences in parameters were observed between MII-pH and HMII-pH monitoring. The correlation analysis demonstrated a significant negative correlation between the hypopharyngeal BI values and Hyodo scores. The optimal cutoff value for hypopharyngeal BI was 1552 Ω.ConclusionsThis study demonstrated the usefulness of HMII-pH monitoring in identifying NIP with pathological LPR. Considering the difficulties in performing examinations in NIPs, HMII-pH monitoring may be a potentially useful technique for the simultaneous evaluation of swallowing dysfunction, LPR, and GERD in NIP.

“Gas” laryngopharyngeal reflux cause unexplained chronic cough

Hypopharyngeal multichannel intraluminal impedance (HMII) that can measure laryngopharyngeal reflux (LPR) events has supported the causal relationship between chronic cough (CC) and LPR containing liquid. However the role of “gas” LPR associated with CC has been poorly understood. We present two cases of patients with CC who had negative LPR containing liquid but had multiple episodes of “gas” LPR on HMII. The majority of “gas” LPR events had a minor pH drop at hypopharynx. Since any etiology of CC was excluded and medical therapy failed, both patients underwent laparoscopic antireflux surgery (LARS). Both of the patients had complete resolution of cough postoperatively. The present cases demonstrated successful outcome of LARS to treat the patients with CC who had documented “gas” LPR on HMII, thus suggesting the causal relationship between CC and “gas” LPR. The number of “gas” LPR events may need to be considered as an important diagnostic parameter.

Sep70/Pepsin expression in hypopharynx combined with hypopharyngeal multichannel intraluminal impedance increases diagnostic sensitivity of laryngopharyngeal reflux.

Improved methods of diagnosis of laryngopharyngeal reflux (LPR) would enable surgeons to better identify patients who may benefit from antireflux surgery (ARS). The objective of the present study was to assess if hypopharyngeal Pepsin and Sep70 expression combined with hypopharyngeal multichannel intraluminal impedance (HMII) has the potential to increase diagnostic sensitivity of LPR. This study was performed on patients who underwent unsedated transnasal endoscopy with hypopharyngeal biopsy and 24-h HMII to determine abnormal proximal exposure (APE) and DeMeester score (DMS) from 2013 to 2016. Pepsin and Sep70 protein expression was assessed by Western blots of biopsy specimens. The outcomes of ARS were assessed using reflux symptom index (RSI). HMII APE classification, Sep 70, and Pepsin protein levels were compared in normative and symptomatic LPR patients and further analyzed alongside quality of life changes following ARS. Of 30 subjects enrolled, 23 were excluded for abnormal HMII results or endoscopic evidence of esophagitis. Seven subjects and 105 patients were included in the normative and symptomatic groups, respectively. Compared to the normative group, only Pepsin expression was significantly higher in the symptomatic group [APE+/LPR+ (p = 0.000), APE+/LPR- (p = 0.001), and APE- (p = 0.047)]. Further, the ratio of Sep70/Pepsin was significantly lower in the symptomatic group [APE+/LPR+ (p = 0.008), APE+/LPR- (p = 0.000), and APE- (p = 0.050)], and a cutoff ratio for a diagnosis of LPR was established as < 158. Of 105 symptomatic patients, 48 patients underwent ARS. Of these, 17 patients had complete pre- and post-RSI questionnaires. LPR symptoms improved in 15 (88%), of whom 2 were APE- but met criteria for a diagnosis of LPR based on the Sep70/Pepsin cutoff. The identified Sep70/Pepsin ratio may serve as a reliable biomarker for the diagnosis of LPR. As a result, this may help identify additional patients who have a false-negative HMII result due to the 24-h testing window.

Hypopharyngeal multichannel intraluminal impedance leads to the promising outcome of antireflux surgery in Japanese population with laryngopharyngeal reflux symptoms.

Clinical characteristics of laryngopharyngeal reflux (LPR) in Japanese population remain unclear, and its treatment outcome is suboptimal. The objectives of this study were to evaluate Japanese patients with LPR symptoms using hypopharyngeal multichannel intraluminal impedance (HMII) and to assess the outcome of antireflux surgery (ARS). Subjects included patients who had LPR symptoms for > 12 weeks or laryngoscopic findings suggestive of LPR and underwent laryngoscopy and esophageal testing including HMII. Abnormal proximal exposure (APE) was defined as LPR ≥ 1/day and/or full column reflux (FCR) (reflux 2cm distal to the upper esophageal sphincter) ≥ 5/day on HMII. Patients with APE were offered ARS and the outcome of ARS was objectively assessed using Reflux Symptom Index (RSI). From July 2015 to September 2016, 52 patients with LPR symptoms (28 men, 24 women, median BMI 22.3) underwent HMII, and 38 patients (73%) had APE. Of them, 29 (76%) patients were not obese (BMI < 25) and 19 (50%) patients had a negative DeMeester score. Approximately one-third of LPR and FCR events were non-acid in the distal esophagus. A positive symptom-association probability was seen only in 18 patients (35%). Mild esophagitis and hiatal hernia were found in 5 (10%) and 23 (48%) patients, respectively. All 12 patients (100%) who had undergone ARS were able to discontinue PPI and had a significant improvement in the RSI scores postoperatively (22.9 ± 10.0 vs. 6.8 ± 6.8, p <.001). APE was frequently observed in Japanese patients with LPR symptoms. Obesity and esophagitis were uncommon in this population. Since a large number of patients with APE had negative DeMeester score and proximal reflux events were often non-acid, a conventional pH monitoring is insufficient. HMII is crucial to evaluate patients with LPR symptoms as the documentation of APE is a key for successful outcome of ARS.

Hypopharyngeal pepsin and Sep70 as diagnostic markers of laryngopharyngeal reflux: preliminary study.

The management of laryngopharyngeal reflux (LPR) has been challenging. Hypopharyngeal multichannel intraluminal impedance (HMII) has shown to increase the sensitivity in diagnosing LPR. The objective of this study is to investigate the potential use of pepsin and Sep70 as diagnostic tools for detection of LPR in combination with HMII. Tissue samples of hypopharynx, distal esophagus, and gastric cardia were collected from patients with LPR symptoms regardless of gastroesophageal reflux (GERD) diagnosis and underwent HMII to detect LPR and high esophageal reflux (HER: reflux 2 cm distal to upper esophageal sphincter) events. Patients were classified into two groups based on the presence of abnormal proximal exposure (APE), which was defined as LPR ≥1/day and/or HER ≥5/day: (1) positive-APE and (2) negative-APE. Patients with typical GERD symptoms without LPR symptoms who did not undergo HMII were used as a "control" GERD group. Protein was isolated from tissue samples and Western blot analysis of pepsin and Sep70 was performed. Pepsinogen was used as a control to differentiate pepsin from pepsinogen. Relative quantitation was performed using Image Studio Lite Software with normalization against the internal actin of each blot. From October 2012 to September 2013, 55 patients underwent HMII. Of 55, 20 patients underwent biopsies from hypopharynx (17 positive-APE and 3 negative-APE). Ten patients with typical GERD symptoms were identified from tissue bank as a "control" GERD group. Pepsin was detected in distal esophagus and hypopharynx in all groups without significant difference among groups. However, Sep70 in distal esophagus and hypopharynx was significantly depleted in the positive-APE group compared to the other groups (p = 0.032 and 0.002, respectively). Depletion of Sep70 with the presence of pepsin in the hypopharynx may indicate cellular injury in laryngopharynx due to constant proximal reflux. However, the normative data for these markers have to be validated.

Tu1606 Hypopharyngeal Multichannel Intraluminal Impedance Improves the Outcome of Antireflux Surgery on Patients With Laryngeal Symptoms

Introduction: Patient selection is critical for the successful surgical treatment of gastroesophageal reflux disease (GERD). Previously, we established the normative data of laryngopharyngeal reflux (LPR) and high-esophageal reflux (HER: reflux up to 2cm distal to upper esophageal sphincter) events for 24-hour hypopharyngeal multichannel intraluminal impedance (HMII). Based on the data, we have constructed the criteria to define abnormal proximal exposure (APE) as LPR ≥1/day and/or HER ≥5/day. Previous retrospective analyses have suggested that HMII may increase the sensitivity in selecting patients with LPR symptoms who likely respond antireflux surgery (ARS). The purpose of this study was to objectively evaluate the outcome of ARS on patients selected based on our criteria by using validated questionnaires. Methods: This is a retrospective review of prospectively collected data from patients who underwent HMII. Patients with APE as measured by HMII and subsequently underwent ARS, were identified. The outcome of surgery included improvement in clinical symptoms and quality of life, both of which were assessed based on the personal interview and the validated questionnaires such as GERD-HRQL, Respiratory Symptom Index (RSI) and SF-36 before and after ARS. Results: From September 2012 to October 2013, 171 patients underwent HMII. Of 118 patients with APE, 26 patients underwent ARS (7 men and 19 women; mean age 51.6). Twenty-one patients (81%) had LPR symptoms including cough (n=20), throat burning (n=3), cervical dysphagia (n=3), throat tightness/pressure (n= 2), and hoarseness (n=1). Of 21 with LPR symptoms, 11 (42%) had concomitant typical GERD symptom such as heartburn and regurgitation. The mean DeMeester score was 15.7 (range 1-54.8) and 15 patients (58%) had negative DeMeester score. Clinical symptoms completely resolved in 20 patients (77%) and significantly improved in 5 patients (19%) at 6 weeks after the surgery. Anti-secretory medications were discontinued in 25 patients (96%) at a mean follow-up period of 2.1 months (0.36-5.3). Complete validated questionnaires before and after ARS were available for 11 patients. Of them, there was a significant improvement in GERD-HRQL (Pre-op 20.7; post-op 6.9, p= 0.016) and RSI scores (Pre-op 23.9; post-op 15, p=0.001) post-operatively. However, there was no significant difference in SF-36 scores on either physical component scores (pre-op 33.6; post-op 32.8, p=0.853) or mental component scores (pre-op 44.7; post-op 47.5, p=0.49). Conclusion: APE as measured by HMII, regardless of whether there is positive DeMeester score, may identify patients with laryngeal symptoms, who likely respond ARS, potentially improving the surgical outcome. Data set is currently being expanded and will be presented at the conference.

Preoperative Diagnostic Workup before Antireflux Surgery: An Evidence and Experience-Based Consensus of the Esophageal Diagnostic Advisory Panel

Gastroesophageal reflux disease (GERD) is a very prevalent disorder. Medical therapy improves symptoms in some but not all patients. Antireflux surgery is an excellent option for patients with persistent symptoms such as regurgitation, as well as for those with complete symptomatic resolution on acid-suppressive therapy. However, proper patient selection is critical to achieve excellent outcomes. A panel of experts was assembled to review data and personal experience with regard to appropriate preoperative evaluation for antireflux surgery and to construct an evidence and experience-based consensus that has practical application. The presence of reflux symptoms alone is not sufficient to support a diagnosis of GERD before antireflux surgery. Esophageal objective testing is required to physiologically and anatomically evaluate the presence and severity of GERD in all patients being considered for surgical intervention. It is critical to document the presence of abnormal distal esophageal acid exposure, especially when antireflux surgery is considered, and reflux-related symptoms should be severe enough to outweigh the potential side effects of fundoplication. Each testing modality has a specific role in the diagnosis and workup of GERD, and no single test alone can provide the entire clinical picture. Results of testing are combined to document the presence and extent of the disease and assist in planning the operative approach. Currently, upper endoscopy, barium esophagram, pH testing, and manometry are required for preoperative workup for antireflux surgery. Additional studies with long-term follow-up are required to evaluate the diagnostic and therapeutic benefit of new technologies, such as oropharyngeal pH testing, multichannel intraluminal impedance, and hypopharyngeal multichannel intraluminal impedance, in the context of patient selection for antireflux surgery.

Antireflux Surgery in Patients With Chronic Cough and Abnormal Proximal Exposure as Measured by Hypopharyngeal Multichannel Intraluminal Impedance

Chronic cough is a laryngeal symptom that can be caused by gastroesophageal reflux disease; however, treatment outcome has been difficult to predict because of the lack of an objective testing modality that accurately detects reflux-related cough. To define the patterns of reflux and assess the outcome of antireflux surgery (ARS) in patients with chronic cough who were selected using hypopharyngeal multichannel intraluminal impedance (HMII). Review of prospectively collected data. Tertiary care university hospital. Patients with chronic cough, which was defined as persistent cough (≥8 weeks) of unknown cause. Hypopharyngeal multichannel intraluminal impedance with a specialized catheter to detect laryngopharyngeal reflux and high-esophageal reflux (reflux 2 cm distal to the upper esophageal sphincter) and ARS. Abnormal proximal exposure was defined as laryngopharyngeal reflux occurring 1 or more times per day and/or high-esophageal reflux occurring 5 or more times per day. The outcomes of ARS included symptomatic improvement. From October 2009 to June 2011, a total of 314 symptomatic patients underwent HMII. Of this population, 49 patients (15 men, 34 women; median age, 57 years) were identified as having chronic cough. Of the 49 participants, 23 of 44 patients (52%) had objective findings of gastroesophageal reflux disease, such as esophagitis. Abnormal proximal exposure was discovered in 36 of the 49 patients (73%). Of 16 patients with abnormal proximal exposure who subsequently underwent ARS, 13 patients (81%) had resolution of cough and 3 patients (19%) had significant improvement at a median follow-up of 4.6 months (range, 0.5-13 months). A highly selective group of patients with idiopathic chronic cough may have abnormal proximal exposure to gastroesophageal reflux documented by HMII that would have not been detected with conventional pH testing. Thus, HMII is likely to improve the sensitivity of laryngopharyngeal reflux diagnosis and better elucidate those who will respond to antireflux surgery.

Proximal Reflux as a Cause of Adult-Onset Asthma

To determine the patterns and proximity of reflux events in patients with adult-onset asthma (AOA) using hypopharyngeal multichannel intraluminal impedance (HMII) and to assess outcomes of antireflux surgery (ARS) in patients with AOA. DESIGN Retrospective review of prospectively collected data. University hospital. PATIENTS, INTERVENTIONS, AND OUTCOMES: All patients with AOA referred to our testing center underwent HMII, and those with abnormal proximal exposure, defined as laryngopharyngeal reflux at least once a day and/or high esophageal reflux at least 5 times a day, subsequently underwent ARS. From October 1, 2009, through June 30, 2011, a total of 31 patients with AOA (4 men and 27 women; mean age, 53 years) underwent HMII. Of 27 patients with available information, 11 (41%) had objective evidence of reflux disease. Nineteen patients (70%) had concomitant typical reflux symptoms. Despite a frequently negative DeMeester score, abnormal proximal exposure, which occurred in the upright position, was observed in 19 patients (70%). Of 20 patients who subsequently underwent ARS, asthma symptoms improved in 18 (90%), and 6 of them discontinued or reduced pulmonary medications at a mean (range) follow-up of 4.6 (0.6-15.2) months. Pulmonary function test results before and after ARS revealed that of 5 patients, 4 (80%) had improvement of the forced expiratory volume in the first second of expiration and/or the peak expiratory flow rate, which correlated with symptomatic improvement. Adult-onset asthma is associated with abnormal proximal exposure of the aerodigestive tract to refluxate; these patients respond to ARS despite negative pH test results. Patients with AOA should undergo testing with HMII because they would not be detected with conventional pH testing.

Gastroesophageal reflux disease and patterns of reflux in patients with idiopathic pulmonary fibrosis using hypopharyngeal multichannel intraluminal impedance

Idiopathic pulmonary fibrosis (IPF) is a diffuse fibrotic lung disease of unknown etiology. The association between IPF and gastroesophageal reflux disease (GERD) has been suggested. The objective of this study was to determine the prevalence of GERD and assess the proximity of reflux events in patients with histologically proven IPF using hypopharyngeal multichannel intraluminal impedance (HMII). This is a retrospective review of prospectively collected data from patients with histologically confirmed IPF (via lung biopsy) who underwent objective esophageal physiology testing including high-resolution manometry and HMII. Defective lower esophageal sphincter (LES) was defined as either LES pressure of <5.0 mmHg, total length of LES of <2.4 cm, or intra-abdominal length of LES of <0.9 cm. Abnormal esophageal motility was considered present when failed swallows ≥30% and/or mean wave amplitude <30 mmHg was present. HMII used a specialized impedance catheter to directly measure laryngopharyngeal reflux (LPR) and full column reflux (reflux 2 cm distal to the upper esophageal sphincter). Based on the previous study of healthy subjects, abnormal proximal exposure was considered present when LPR ≥1/day and/or full column reflux ≥5/day were present. From October 2009 to June 2011, 46 patients were identified as having pulmonary fibrosis and sufficient HMII data. Of 46, 10 patients were excluded because of concomitant connective tissue diseases, and 8 patients were excluded because they had undergone lung transplantation, which may impact the patterns of reflux. The remaining 28 patients with histologically confirmed IPF (male 16, female 12) were included in this study. Mean age and BMI were 60.4 years (range, 41-78) and 28.4 (range, 21.1-38.1), respectively. All patients except one were symptomatic; 23 (82%) patients had concomitant typical GERD symptoms such as heartburn, whereas 4 (14%) patients had isolated pulmonary symptoms such as cough. Esophageal mucosal injury such as esophagitis and Barrett's esophagus was found in 17 (71%) patients, whereas hiatal hernia was found in 19 (73%) patients. Abnormal proximal exposure, which occurred almost exclusively in the upright position, was present in 54% (15/28) of patients. There was no significant difference in clinical symptoms, objective findings of GERD, and pulmonary functions such as forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and diffusing capacity of the lung for carbon monoxide (DLCO) between patients with and without abnormal proximal exposure. Although the total number of reflux events was significantly higher in patients with abnormal proximal exposure, a large number of patients had a negative DeMeester score regardless of whether abnormal proximal exposure was present (patients with, 80%; those without, 85%). Patients with abnormal proximal exposure more likely had a defective LES compared with those without (93% vs. 75%). Fourteen patients (56%) had abnormal esophageal motility including aperistaltic esophagus (n = 9). This first study of HMII in patients with IPF demonstrated that GERD is highly prevalent (>70%), and abnormal proximal reflux events such as LPR and full column reflux are common despite a frequently negative DeMeester score. HMII may be beneficial in the work-up of GERD in patients with IPF.

Mo1485 Short-Term Outcome of Antireflux Surgery on Patients With Chronic Cough and Abnormal Proximal Exposure as Measured by Hypopharyngeal Multichannel Intraluminal Impedance

Mo1485 Short-Term Outcome of Antireflux Surgery on Patients With Chronic Cough and Abnormal Proximal Exposure as Measured by Hypopharyngeal Multichannel Intraluminal Impedance

Su1529 Is Idiopathic Pulmonary Fibrosis Really Idiopathic?: Patterns of Reflux Analyzed by Bi-Positional High-Resolution Manometry and Hypopharyngeal Multichannel Intraluminal Impedance

Su1529 Is Idiopathic Pulmonary Fibrosis Really Idiopathic?: Patterns of Reflux Analyzed by Bi-Positional High-Resolution Manometry and Hypopharyngeal Multichannel Intraluminal Impedance