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.

BACKGROUND & AIMS: Use of proton pump inhibitors (PPIs) could predispose individuals to small intestinal bacterial overgrowth (SIBO) by altering the intraluminal environment and bacterial flora. There is controversy regarding the risk of SIBO among PPI users because of conflicting results from prior studies. A systematic review and meta-analysis were performed to evaluate the association between PPI use and SIBO, using objective clinical outcome measures.

METHODS: Clinical studies comparing SIBO risk among adult users of PPIs vs nonusers were identified in MEDLINE/PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and the National Institutes of Health Clinical Trials databases through July 2012. Two reviewers independently extracted data on study characteristics and outcomes. The primary metameter was the odds ratio (OR) of SIBO among PPI users vs nonusers. Subgroup analyses were performed to examine the influence of study characteristics, such as SIBO diagnostic modality, on study outcome.

RESULTS: Eleven studies (n = 3134) met inclusion criteria. The pooled OR of SIBO in PPI users vs nonusers was 2.282 (95% confidence interval [CI], 1.238-4.205). No significant single large study or temporal effect was seen. Subgroup analysis revealed an association between SIBO and PPI use in studies that used duodenal or jejunal aspirate cultures to diagnose SIBO (OR, 7.587; 95% CI, 1.805-31.894), but no relationship was found between SIBO and PPI use in studies that used the glucose hydrogen breath test (OR, 1.93; 95% CI, 0.69-5.42). Funnel plot analysis identified 4 outlying studies, indicating the possible presence of publication bias.

CONCLUSIONS: PPI use statistically was associated with SIBO risk, but only when the diagnosis was made by a highly accurate test (duodenal or jejunal aspirate culture). Differences in study results could arise from the use of different tests to diagnose SIBO.

BACKGROUND/AIMS: Lubiprostone, a chloride channel type 2 (ClC-2) activator, was thought to treat constipation by enhancing intestinal secretion. It has been associated with increased intestinal transit and delayed gastric emptying. Structurally similar to prostones with up to 54% prostaglandin E2 activity on prostaglandin E receptor 1 (EP1), lubiprostone may also exert EP1-mediated procontractile effect on intestinal smooth muscles. We investigated lubiprostone's effects on intestinal smooth muscle contractions and pyloric sphincter tone.

METHODS: Isolated murine small intestinal (longitudinal and circular) and pyloric tissues were mounted in organ baths with modified Krebs solution for isometric recording. Basal muscle tension and response to electrical field stimulation (EFS; 2 ms pulses/10 V/6 Hz/30 sec train) were measured with lubiprostone (10(-10)-10(-5) M) ± EP1 antagonist. Significance was established using Student t test and P < 0.05.

RESULTS: Lubiprostone had no effect on the basal tension or EFS-induced contractions of longitudinal muscles. With circular muscles, lubiprostone caused a dose-dependent increase in EFS-induced contractions (2.11 ± 0.88 to 4.43 ± 1.38 N/g, P = 0.020) that was inhibited by pretreatment with EP1 antagonist (1.69 ± 0.70 vs. 4.43 ± 1.38 N/g, P = 0.030). Lubiprostone had no effect on circular muscle basal tension, but it induced a dose-dependent increase in pyloric basal tone (1.07 ± 0.01 to 1.97 ± 0.86 fold increase, P < 0.05) that was inhibited by EP1 antagonist.

CONCLUSIONS: In mice, lubiprostone caused a dose-dependent and EP1-mediated increase in contractility of circular but not longitudinal small intestinal smooth muscles, and in basal tone of the pylorus. These findings suggest another mechanism for lubiprostone's observed clinical effects on gastrointestinal motility.

This paper reporting on techniques for esophageal evaluation and imaging and drugs for esophageal disease includes commentaries on endoscopy techniques including dye-based high-resolution and dye-less high-definition endoscopy; the shift from CT to MRI guidance in tumor delineation for radiation therapy; the role of functional lumen imaging in measuring esophageal distensibility; electrical stimulation of the lower esophageal sphincter (LES) as an alternative to fundoduplication for treatment of gastroesophageal reflux disease (GERD); the morphological findings of reflux esophagitis and esophageal dysmotility on double-contrast esophagography; the value of videofluoroscopy in assessing protecting mechanisms in patients with chronic reflux or swallowing disorders; targeting visceral hypersensitivity in the treatment of refractory GERD; and the symptoms and treatments of nighttime reflux and nocturnal acid breakthrough (NAB).

Diagnosis of eosinophilic esophagitis (EoE) and determination of response to therapy is based on histological assessment of the esophagus, which requires upper endoscopy. In children, in whom a dietary approach is commonly used, multiple endoscopies are needed, because foods are eliminated and then gradually reintroduced. Ideally, noninvasive methods could supplement or replace upper endoscopy to facilitate management. Fractionated exhaled nitric oxide (FeNO) has been proposed as a useful measure for monitoring disease activity in studies of patients with eosinophil-predominant asthma and in other atopic disorders. Thus, we evaluated whether FeNO levels could be a useful biomarker to assess the response to therapy in EoE patients. This study was designed to determine whether there is a change in FeNO levels during treatment with topical corticosteroids and whether changes correlated with clinical response. This was a prospective, multicenter study that enrolled nonasthmatic patients with established EoE. FeNO levels and symptom scores were measured at baseline, biweekly during 6-week swallowed fluticasone treatment, and 4 weeks posttreatment. Twelve patients completed the trial. We found a statistically significant difference between median pre- and posttreatment FeNO levels [20.3 ppb (16.0 -29.0 ppb) vs 17.6 ppb (11.7 -27.3 ppb), [corrected] p=0.009]. However, neither the pretreatment FeNO level, a change of FeNO level after 2 weeks of treatment, nor the FeNO level at the end of treatment confidently predicted a clinical or histological response. Although our findings suggest nitric oxide possibly has a physiological role in EoE, our observations do not support a role of FeNo determination for management of EoE.

BACKGROUND: Gastroesophageal reflux disease occurs frequently among patients with asthma. Therapy with proton pump inhibitors (PPIs) to improve asthma control remains controversial. We sought to evaluate the efficacy of PPIs in treatment of asthma using objective and subjective outcome measures.

METHODS: A literature search was undertaken using MEDLINE (1950-January 2010), PubMed (1950-January 2010), EMBASE (1980-January 2010), and Cochrane Central Register of Controlled Trials (through January 31, 2010). Randomized, placebo-controlled trials evaluating the efficacy of PPIs for treatment of asthma in adults were selected. The primary outcome of interest was morning peak expiratory flow (PEF) rate. Secondary outcomes included objective (evening PEF rate and forced expiratory volume in 1 second) and subjective (asthma symptoms score and Asthma Quality of Life Questionnaire score) measures. Influence of study characteristics on outcomes was examined by subgroup analyses and meta-regression.

RESULTS: Eleven trials (2524 patients) met inclusion criteria. Overall, patients had a higher mean morning PEF rate after treatment with PPIs compared with placebo (mean difference, 8.68 L/min [95% confidence interval, 2.35-15.02]). No significant single large-study effect, temporal effect, or publication bias was seen. Subgroup analysis revealed a trend toward a larger improvement in morning PEF rate in studies enrolling only patients with gastroesophageal reflux disease (mean difference, 16.90 L/min [95% confidence interval, 0.85-32.95]). Analyses of secondary outcomes (asthma symptoms score, Asthma Quality of Life Questionnaire score, evening PEF rate, and forced expiratory volume in 1 second) showed no significant difference between PPIs and placebo.

CONCLUSIONS: Proton pump inhibitor therapy in adults with asthma results in a small, statistically significant improvement in morning PEF rate. The magnitude of this improvement, however, is unlikely to be of meaningful clinical significance. There is insufficient evidence to recommend empirical use of PPIs for routine treatment of asthma.