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.

BACKGROUND: The value of esophageal manometry and ambulatory pH monitoring before laparoscopic antireflux surgery (LARS) has been questioned because tailoring the operation to the degree of hypomotility often is not required. This study evaluated a consecutive cohort of patients referred for esophageal function studies in preparation for LARS to determine the rates of findings that would alter surgical decisions.

METHODS: High-resolution manometry (HRM) was performed for each subject using a 21-lumen water-perfused system, and motor function was characterized. Gastroesophageal reflux disease (GERD) was evident from ambulatory pH monitoring if thresholds for acid exposure time and/or positive symptom association probability were passed.

RESULTS: Of 1,081 subjects (age, 48.4 ± 0.4 years; 56.7% female) undergoing preoperative HRM, 723 (66.9%) also had ambulatory pH testing performed. Lower esophageal sphincter (LES) hypotension (38.9%) and nonspecific spastic disorder (NSSD) of the esophageal body (36.1%) were common. Obstructive LES pathophysiology was noted in 2.5% (achalasia in 1%; incomplete LES relaxation in 1.5%), and significant esophageal body hypomotility in 4.5% (aperistalsis in 3.2%; severe hypomotility in 1.3%) of the subjects. Evidence of GERD was absent in 23.9% of the subjects. Spastic disorders were more frequent in the absence of GERD (43.9% vs. 23.1% with GERD; p < 0.0001), whereas hypomotility and normal patterns were more common with GERD.

CONCLUSIONS: Findings considered absolute or relative contraindications for standard 360º fundoplication are detected in 1 of 14 patients receiving preoperative HRM. Additionally, spastic findings associated with persistent postoperative symptoms are detected at esophageal function testing that could be used in preoperative counseling and candidate selection. Physiologic testing remains important in the preoperative evaluation of patients being considered for LARS.