BACKGROUND: Antireflux surgery (ARS) has been associated with improved lung transplant outcomes. Pre-transplant ARS has been shown in small studies to improve pulmonary function among transplant candidates with gastroesophageal reflux disease (GERD). Although early post-transplant ARS has been shown to be effective in reducing chronic rejection, the optimal timing of ARS in transplant recipients remains unclear. The aim of this study is to evaluate the time to early allograft injury among lung transplant recipients by timing of ARS.

METHODS: This was a retrospective cohort study of lung transplant recipients undergoing ARS before or after transplantation at a tertiary care center since 2007, with at least 1-year follow-up. Early allograft injury was defined clinically and histologically as acute rejection or lymphocytic bronchiolitis, occurring within the first year after transplantation. In accordance with prior studies, the cutoff between early and late post-transplant ARS was set at 6 months. Time-to-event analysis using the Cox proportional hazards model was applied to assess the relationship between timing of surgery and early allograft injury. Subjects not meeting this outcome were censored at 1 year in the time-to-event analysis. Fisher’s exact test for binary variables and Student’s t test for continuous variables were performed to assess for differences among the three groups: ARS pre-transplant, ARS early post-transplant, and ARS late post-transplant.

RESULTS: Forty-eight subjects (60% men, mean age 55) met the inclusion criteria for the study. Patient demographics, pre-transplant cardiopulmonary function, BMI, CMV status, and PPI exposure were similar between groups. Kaplan-Meier analysis demonstrated significantly increased early allograft injury in late post-transplant ARS patients compared with both pre-transplant (log-rank p = 0.007) and early post-transplant (log-rank p = 0.05) patients, as well as a significant trend across groups (log-rank p = 0.005). No significant difference between pre- and early post-transplant groups was noted. Three ARS failures were noted in the pre- and late post-transplant groups. Complications included one death due to aspiration pneumonia in a late post-transplant ARS recipient. No early post-transplant ARS patients experienced ARS failure or complications.

CONCLUSION: Late post-lung transplant ARS resulted in increased risk of early allograft injury compared to pre-transplant and early post-transplant ARS. Both pre- and early post-transplant ARS appear equally safe and effective in improving lung transplant outcomes. These findings support consideration of aggressive reflux testing and application of antireflux measures before or soon after transplantation to minimize the impact of reflux on allograft injury.

The upper esophageal sphincter constitutes an important anatomic and functional landmark in the physiology of pharyngeal swallowing. A variety of clinical circumstances may call for a dedicated evaluation of this mechanism, from the etiologic evaluation of indeterminate symptoms to the generation of complex locoregional therapeutic strategies. Multiple diagnostic tools exist for the assessment of pharyngeal swallowing generally and of upper esophageal sphincter function specifically, some well established and others not yet settled into routine practice. This report reviews five specific modalities for use in making this assessment, outlining the strengths, weaknesses, and logistical considerations of each with respect to its potential use in clinical settings. In many cases, these studies will provide complementary information regarding pharyngeal function, suggesting the relative advantage of a multimodal evaluation.

BACKGROUND: Gastroesophageal reflux disease has been associated with poor outcomes following lung transplantation. However, the association between pretransplant reflux and post-transplant readmission, an indicator of early clinical outcome, has not been previously assessed.

METHODS: This was a retrospective cohort study of lung transplant recipients undergoing pretransplant multichannel intraluminal impedance and pH (MII-pH) study off acid suppression at a tertiary care center since 2007. Subjects with pretransplant fundoplication were excluded. Time to readmission was defined as duration from post-transplant discharge to next hospital admission for any reason. Subgroup analysis was performed to exclude elective readmissions. Time-to-event analysis was performed using Cox proportional hazards model, with appropriate censoring.

KEY RESULTS: Forty-three subjects (60% men, mean age: 57, median follow-up: 1.7 years) met inclusion criteria for the study. Patient demographics and pretransplant cardiopulmonary function were similar between readmission cohorts. Time to all-cause readmission was associated with increased distal acid episodes (HR: 3.15, p = 0.04) and proximal acid episodes (HR: 3.61, p = 0.008) on impedance, increased acid exposure on pH (HR: 2.22, p = 0.04), and elevated Demeester score (HR: 2.26, p = 0.03). When elective readmissions were excluded, early readmission remained significantly associated with increased proximal acid reflux episodes (HR: 2.49, p = 0.04). All findings were confirmed on Kaplan-Meier analysis.

CONCLUSIONS & INFERENCES: Elevated proximal acid reflux on pretransplant MII-pH testing was associated with early readmission following lung transplantation, even after excluding elective readmissions. Exposure to severe acid reflux has measurable effects on early postoperative outcomes such as readmission, and aggressive early antireflux therapy should be considered.

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.

BACKGROUND: Gastroesophageal reflux (GER) has been associated with idiopathic pulmonary fibrosis (IPF), although the mechanism remains unclear. Gastroesophageal reflux/microaspiration may lead to lung fibrosis, while increased pulmonary workload may also worsen GER. Comparing the GER profile of IPF patients to chronic obstructive pulmonary disease (COPD) patients with similar lung function may help delineate the role of GER in IPF pathogenesis.

METHODS: This was a retrospective cohort study of IPF and COPD patients undergoing pre-lung transplant multichannel intraluminal impedance and pH study (MII-pH) off acid suppression at a tertiary center in 2008-2014. Patients with prior fundoplication were excluded. Baseline demographics, pulmonary function test, and MII-pH results were recorded. Univariate analyses were performed using Fisher's exact (binary variables) and Student's t (continuous variables) tests. Logistic regression was performed to adjust for potential confounders.

KEY RESULTS: A total of 90 subjects (54 IPF, 36 COPD) met inclusion criteria. Compared to COPD, IPF patients had increased total reflux episodes (65.9 vs 46.1, p = 0.02), proximal reflux episodes (30.3 vs 20.3, p = 0.04), and prevalence of abnormal total reflux episodes (38.9% vs 16.7%, p = 0.02). On multivariate analyses, abnormal total reflux episodes (OR: 4.9, p = 0.05) and bolus reflux exposure time (OR: 4, p = 0.04) remained significantly associated with IPF.

CONCLUSIONS & INFERENCES: Abnormal reflux was significantly more prevalent among IPF patients after controlling for lung disease severity. Gastroesophageal reflux/microaspiration likely plays a role in fibrosis in IPF. A significant portion of IPF patients had increased non-acid reflux. Therapies aiming to prevent reflux of gastric contents may be more beneficial than antisecretory medications alone in these patients.

Eosinophilic esophagitis (EoE) is an increasingly diagnosed, immune-mediated disease characterized by inflammation of the esophagus in both children and adult, causing significant morbidity. Adults typically present with dysphagia and a history of food impaction. Diagnosis should be considered in patients with histological evidence of eosinophilia (≥15 eosinophils per high-power field) on esophageal biopsy. More recently, it has been observed that a significant percentage of patients with esophageal eosinophilia respond both clinically and histologically to PPI therapy. This disorder has been named PPI-responsive esophageal eosinophilia (PPI-REE). Recent studies suggest that patients with PPI-REE have similar clinical and endoscopic features of patients with EoE. Specifically, both PPI-REE and EoE patients have a strong disposition to allergy compared to patients without eosinophilia. As such, PPI-REE may represent a subset or variant of EoE. Effective treatment of EoE requires a multidisciplinary approach with gastroenterologists, pathologists, allergists, and nutritionists. Treatments include elimination and elemental diets, topical glucocorticoids (fluticasone and budesonide), and endoscopic dilation.

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.

Gastroesophageal reflux disease (GERD) is highly associated with a range of respiratory symptoms, arising from a variety of etiologies. The following commentaries on respiratory manifestations of GERD address evidence for a role of a vagally mediated bronchoconstriction reflex in the development of asthma; the direct effects of airway obstruction on lower esophageal sphincter (LES) pressure and reflux episodes; the mechanisms by which reflux may play roles in chronic cough and airway stenosis; the limited efficacy of laparoscopic antireflux surgery (LARS) in improving GERD-related respiratory symptoms; the search for a marker for microaspiration and reflux-induced airway disease; and the potential of proton pump inhibitor (PPI) treatment for patients presenting with asthma and GERD.

In patients with laryngopharygeal reflux (LPR), gastric contents exhibit retrograde flow into the upper aero-digestive tract, causing extraesophageal symptoms including chronic cough, hoarseness, indigestion, difficulty swallowing, globus pharyngis, and asthma. The following on laryngopharyngeal reflux includes commentaries on the use of patient-completed questionaires and anti-human pepsin antibodies and other non-invasive tests in diagnosis; the role of pepsin and acid in the etiologies of laryngeal cancers; and the application of proton pump inhibitor (PPI) therapy for the treatment of LPR.