Failed Swallows on High-Resolution Manometry Independently Correlates With Severity of LPR Symptoms.

BACKGROUND: Abnormal esophageal motility is prevalent in gastroesophageal reflux disease patients; however, its relationship with laryngopharyngeal reflux (LPR) symptom severity remains unclear. Altered esophageal transit may contribute to LPR symptoms. We aimed to examine the relationship between reflux symptom index (RSI), a validated questionnaire for LPR symptoms, and abnormal esophageal motility on high-resolution manometry (HRM). METHODS: A total of 133 consecutive patients (55.9 ± 14.6 years, 69.9% female) with suspected LPR referred for HRM and multichannel intraluminal impedance-pH study (MII-pH) at a tertiary center from March 2015 to October 2017 were included. RSI questionnaire was prospectively collected prior to motility testing. Authors analyzing HRM and MII-pH were blinded to RSI findings. Statistical analyses were performed using Student's t test or Pearson's correlation (univariate) and general linear regression (multivariable). RESULTS: Mean RSI was higher among patients with ineffective esophageal motility than those with normal motility (23.7 vs 18.6, P = 0.01). Significant positive correlation was found between RSI and percent failed swallows (R2 = 0.21, P = 0.03), but not percent weak swallows. On multivariable analysis, percent ineffective (failed or weak) swallows was significantly associated with RSI (ß-coefficient: 0.072, P = 0.05) after controlling for age, gender, BMI, smoking, prior PPI use, and reflux on MII-pH. When analyzed separately, percent failed swallows (ß-coefficient: 0.095, P= 0.02), but not percent weak swallows, independently predicted higher RSI. CONCLUSIONS: Ineffective swallows, particularly failed swallows, are independently associated with higher RSI in patients with suspected LPR, even after controlling for reflux on MII-pH. Esophageal dysmotility may play a role in suspected LPR symptoms independent of reflux. HRM should be routinely considered in evaluating these patients.

Increased Acid Exposure on Pretransplant Impedance-pH Testing Is Associated With Chronic Rejection After Lung Transplantation.

GOAL: The goal of this study was to assess the relationship between pretransplant measures of reflux and longer-term outcomes of chronic allograft rejection in lung transplant recipients. BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is a primary measure of morbidity and mortality following lung transplantation, and a manifestation of chronic lung allograft dysfunction (CLAD). Acid reflux has been associated with early allograft injury through a proposed mechanism of aspiration and activation of the inflammatory cascade, but its association with chronic rejection is unclear. STUDY: This was a retrospective cohort study of lung transplant recipients undergoing impedance-pH testing off proton pump inhibitor from 2007 to 2016. Patients with pretransplant antireflux surgery were excluded. Time-to-event analysis using the Cox proportional hazards model was applied to assess the relationship between pretransplant reflux measures and the development of BOS, defined histologically and clinically. A secondary analysis was completed using CLAD as the outcome variable. RESULTS: Fifty-one subjects (59% men, mean age: 56, mean follow-up: 2.2 y) met inclusion criteria for the study. The BOS endpoint was reached in 13 subjects (28%). In time-to-event analyses, BOS was associated with increased acid exposure, defined as >4.2% of time with pH<4 [hazard ratio (HR): 4.18; 95% confidence interval (CI): 1.31-13.4; P=0.01], and elevated DeMeester score >14.7 (HR: 3.08; 95% CI: 1.02-9.26; P=0.04), with confirmation from Kaplan-Meier analyses. The secondary analysis demonstrated a similar association between increased acid exposure and CLAD (HR: 3.28; 95% CI: 1.09-9.88; P=0.03), which persisted on multivariate models. CONCLUSION: Increased acid exposure on pretransplant reflux testing was associated with the development of BOS and CLAD, both measures of chronic allograft rejection, after lung transplantation, and may provide clinically relevant information to improve lung allograft survival through aggressive reflux management.

Abnormal Bolus Reflux Is Associated With Poor Pulmonary Outcome in Patients With Idiopathic Pulmonary Fibrosis.

BACKGROUND/AIMS: Gastroesophageal reflux (GER) is postulated to play a role in idiopathic pulmonary fibrosis (IPF). However, the value of objective GER measures in predicting IPF disease progression is unclear. We aim to evaluate the association between objective GER measures on multichannel intraluminal impedance and pH (MII-pH) testing and development of poor pulmonary outcomes within 1 year in prelung transplant IPF patients. METHODS: This was a retrospective cohort study of adults with IPF who underwent pre-lung transplant evaluation with MII-pH off proton pump inhibitors (PPI) at a tertiary care center from June 2008 to November 2015. Patients were followed for 1 year from time of MII-pH for poor pulmonary outcomes, defined by hospitalization for respiratory exacerbation or death. Univariate, multivariate and time-to-event analyses were performed to assess associations between baseline GER parameters on MII-pH and poor outcomes. RESULTS: Eighty-four subjects (mean age 61.1 years, 64.3% male) were included. Subjects with increased bolus exposure time (BET) had a higher incidence of 1-year poor pulmonary outcome vs normal BET (45.7% vs 15.2%, P = 0.006). Increased BET remained an independent predictor of poor outcome after controlling for age, gender, body mass index, smoking, lung disease severity, and PPI use (OR, 4.18; P = 0.030). Increased BET was also predictive of decreased time to poor pulmonary outcome (hazard ratio [HR], 4.88; P = 0.007). Subgroup analyses showed that increased BET remained independently associated with time to pulmonary hospitalization (HR, 4.00; P = 0.020), with a trend for 1-year mortality (HR, 2.19; P = 0.380). CONCLUSION: Increased BET on MII-pH is an independent predictor of poor pulmonary outcome over 1 year in IPF patients.

Pre-lung transplant measures of reflux on impedance are superior to pH testing alone in predicting early allograft injury.

AIM: To evaluate pre-lung transplant acid reflux on pH-testing vs corresponding bolus reflux on multichannel intraluminal impedance (MII) to predict early allograft injury. METHODS: This was a retrospective cohort study of lung transplant recipients who underwent pre-transplant combined MII-pH-testing at a tertiary care center from January 2007 to November 2012. Patients with pre-transplant fundoplication were excluded. Time-to-event analysis was performed using a Cox proportional hazards model to assess associations between measures of reflux on MII-pH testing and early allograft injury. Area under the receiver operating characteristic (ROC) curve (c-statistic) of the Cox model was calculated to assess the predictive value of each reflux parameter for early allograft injury. Six pH-testing parameters and their corresponding MII measures were specified a priori. The pH parameters were upright, recumbent, and overall acid reflux exposure; elevated acid reflux exposure; total acid reflux episodes; and acid clearance time. The corresponding MII measures were upright, recumbent, and overall bolus reflux exposure; elevated bolus reflux exposure; total bolus reflux episodes; and bolus clearance time. RESULTS: Thirty-two subjects (47% men, mean age: 55 years old) met the inclusion criteria of the study. Idiopathic pulmonary fibrosis (46.9%) represented the most common pulmonary diagnosis leading to transplantation. Baseline demographics, pre-transplant cardiopulmonary function, number of lungs transplanted (unilateral vs bilateral), and post-transplant proton pump inhibitor use were similar between reflux severity groups. The area under the ROC curve, or c-statistic, of each acid reflux parameter on pre-transplant pH-testing was lower than its bolus reflux counterpart on MII in the prediction of early allograft injury. In addition, the development of early allograft injury was significantly associated with three pre-transplant MII measures of bolus reflux: overall reflux exposure (HR = 1.18, 95%CI: 1.01-1.36, P = 0.03), recumbent reflux exposure (HR = 1.25, 95%CI: 1.04-1.50, P = 0.01) and bolus clearance (HR = 1.09, 95%CI: 1.01-1.17, P = 0.02), but not with any pH-testing parameter measuring acid reflux alone. CONCLUSION: Pre-transplant MII measures of bolus reflux perform better than their pH-testing counterparts in predicting early allograft injury post-lung transplantation.

Pre-transplant impedance measures of reflux are associated with early allograft injury after lung transplantation.

BACKGROUND: Acid reflux has been associated with poorer outcomes after lung transplantation. Standard pre-transplant reflux assessment has not been universally adopted. Non-acid reflux may also induce a pulmonary inflammatory cascade, leading to acute and chronic rejection. Esophageal multichannel intraluminal impedance and pH testing (MII-pH) may be valuable in standard pre-transplant evaluation. We assessed the association between pre-transplant MII-pH measures and early allograft injury in lung transplant patients. METHODS: This was a retrospective cohort study of lung transplant recipients who underwent pre-transplant MII-pH at a tertiary center from 2007 to 2012. Results from pre-transplant MII-pH, cardiopulmonary function testing, and results of biopsy specimen analysis of the transplanted lung were recorded. Time-to-event analyses were performed using Cox proportional hazards and Kaplan-Maier methods to assess the associations between MII-pH measures and development of acute rejection or lymphocytic bronchiolitis. RESULTS: Thirty patients (46.7% men; age, 54.2 years) met the inclusion criteria. Pre-transplant cardiopulmonary function and pulmonary diagnoses were similar between outcome groups. Prolonged bolus clearance (hazard ratio [HR], 4.11; 95% confidence interval [CI], 1.34-12.57; p = 0.01), increased total distal reflux episodes (HR, 4.80; 95% CI, 1.33-17.25; p = 0.02), and increased total proximal reflux episodes (HR, 4.43; 95% CI, 1.14-17.31; p = 0.03) were significantly associated with decreased time to early allograft injury. Kaplan-Meier curves also demonstrated differences in time to rejection by prolonged bolus clearance (p = 0.01) and increased total distal reflux episodes (p = 0.01). Sub-group analysis including only patients with MII-pH performed off proton pump inhibitors (n = 24) showed similar results. CONCLUSIONS: Prolonged bolus clearance, increased total distal reflux episodes, and increased total proximal reflux episodes on pre-transplant MII-pH were associated with decreased time to early allograft injury after lung transplantation. Routine pre-transplant MII-pH may provide clinically relevant data regarding transplant outcomes and peri-transplant care.

Esophageal motility in nonacid reflux compared with acid reflux.

Esophageal motility has been well studied in gastroesophageal reflux disease (GERD) and acid reflux, but not in nonacid reflux. Consecutive patients who had both 24-h multichannel intraluminal impedance-pH (MII-pH) and esophageal motility tests for suspected GERD were studied. Patients were grouped into nonacid refluxers, acid refluxers, and nonrefluxers based on positive symptom correlation and objective findings of acid reflux. Of 96 patients enrolled, 21 patients (22%) were nonacid refluxers, 44 patients (46%) were acid refluxers, and 31 patients (32%) had no objective evidence of reflux. Normal motility was recorded in 86% of nonacid refluxers, 71% of acid refluxers, and 60% of nonrefluxers. Ineffective esophageal motility was seen in 24% of acid refluxers, and 5% of nonacid refluxers (P = 0.11). Symptomatic nonacid reflux events comprised 22% of patients studied for GERD symptoms by MII-pH. Esophageal motility in nonacid reflux is normal 86% of the time.

Endoscopic pH monitoring for patients with suspected or refractory gastroesophageal reflux disease.

BACKGROUND: Wireless pH studies can offer prolonged pH monitoring, which may potentially facilitate the diagnosis and management of patients with gastroesophageal reflux disease (GERD). The aim of the present study was to evaluate the detection rate of abnormal esophageal acid exposure using prolonged pH monitoring in patients with suspected or refractory GERD symptoms. METHODS: Patients undergoing prolonged ambulatory pH studies for the evaluation of GERD-related symptoms were assessed. Patients with a known diagnosis of GERD were tested on medical therapy, while patients with suspected GERD were tested off therapy. The wireless pH capsules were placed during upper endoscopy 6 cm above the squamocolumnar junction. RESULTS: One hundred ninety-one patients underwent a total of 198 pH studies. Fifty ambulatory pH studies (25%) were excluded from the analysis: 27 patients (14%) had insufficient data capture (less than 18 h on at least one day of monitoring), 15 patients had premature capsule release (7%), seven were repeat studies (3.5%) and one had intolerable pain requiring capsule removal (0.5%). There were 115 patients undergoing pH studies who were off medication, and 33 patients were on therapy. For the two groups of patients, results were as follows: 32 (28%) and 22 (67%) patients with normal studies on both days; 58 (50%) and five (15%) patients with abnormal studies on both days; 18 (16%) and three (9%) patients with abnormal studies on day 1 only; and seven (6%) and three (9%) patients with abnormal studies on day 2 only, respectively. CONCLUSIONS: Prolonged 48 h pH monitoring can detect more abnormal esophageal acid exposure but is associated with a significant rate of incomplete studies.