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Background: Supragastric belching (SGB) and aerophagia are behavioral disorders characterized by air induced esophageal distension. SGB is known to be associated with Gastro Esophageal Reflux Disease (GERD). Low Mean Nocturnal Baseline Impedance (MNBI) values support GERD diagnosis. We aimed to assess if chronic esophageal distension by air affects the esophageal mucosa integrity by assessing changes in MNBI. Methods: In a single‐center database study, we searched retrospectively for patients with a diagnosis of pathological SGB (n = 146) or aerophagia (n = 34) based on impedance‐pH reflux monitoring. During the examined period, patients with a conclusive negative diagnosis of SGB and no evidence of aerophagia were used as a control cohort (n = 191). MNBI at 3, 5, and 17 cm over Lower Esophageal Sphincter (LES) was evaluated. GERD was diagnosed if acid exposure time (AET) >6%. All impedance studies of included patients were prospectively reevaluated. Results: GERD was diagnosed in 31.7% patients with SGB, a rate not different in comparison to patients without SGB (30.8%, p = 0.906). MNBI at 3 and 5 cm above the LES was significantly decreased among patients with SGB. SGB was not correlated with MNBI at 3 cm over the LES, (p: 0.086 OR: 1.000 95% CI: 0.999–1.001) when using multivariate analysis. Moreover no difference was spotted as far as MNBI at 3, 5, and 17 cm over the LES is concerned among patients with or without aerophagia. Conclusion: Even if patients with SGB do show lower MNBI values, esophageal distention due to excessive air movement does not directly lead to impairment of esophageal mucosa integrity. [ABSTRACT FROM AUTHOR]

Reflux hypersensitivity (RH) is one of the phenotypes of gastroesophageal reflux disease. The latest Rome IV defines RH as a condition with typical reflux symptoms and positive reflux-symptom association despite normal acid exposure. Subsequently, the Lyon consensus proposed detailed cutoff values for the criteria on the basis of experts’ consensus. Rome IV brought a clear-cut perspective into the pathophysiology of gastroesophageal reflux disease and the importance of esophageal hypersensitivity. This perspective can be supported by the fact that other functional gastrointestinal disorders such as irritable bowel syndrome and functional dyspepsia often overlap with RH. Although several possible pathophysiological mechanisms of esophageal hypersensitivity have been identified, there is still unmet medical needs in terms of treatment for this condition. This review summarizes the current knowledge regarding RH. [ABSTRACT FROM AUTHOR]

The article offers information about the gastroesophageal reflux disease, responding to proton pump inhibitor (PPI) treatment by the patient. It mentions that indications for prolonged wireless pH monitoring, along with information on the specific advantages and disadvantages of two reflux monitoring techniques.

Background/Aims: Supragastric belching (SGB) is a phenomenon during which air is sucked into the esophagus and then rapidly expelled through the mouth. Patients often complain of severely impaired quality of life. Our objective was to establish the prevalence of excessive SGB within a high-volume gastrointestinal physiology unit, and evaluate its association with symptoms, esophageal motility and gastresophageal reflux disease. Methods: We established normal values for SGB by analyzing 24-hour pH-impedance in 40 healthy asymptomatic volunteers. We searched 2950 consecutive patient reports from our upper GI Physiology Unit (from 2010-2013) for SGB. Symptoms were recorded by a standardized questionnaire evaluating for reflux, dysphagia, and dyspepsia symptoms. We reviewed the predom - inant symptoms, 24-hour pH-impedance and high-resolution esophageal manometry results. Results: Excessive SGB was defined as > 13 per 24 hours. We identified 100 patients with excessive SGB. Ninety-five percent of these patients suffered from typical reflux symptoms, 86% reported excessive belching, and 65% reported dysphagia. Forty-one percent of patients with excessive SGB had pathological acid reflux. Compared to the patients with normal acid exposure these patients trended towards a higher number of SGB episodes. Forty-four percent of patients had esophageal hypomotility. Patients with hypomotility had a significantly higher frequency of SGB compared to those with normal motility (118.3 ± 106.1 vs 80.6 ± 75.7, P = 0.020). Conclusions: Increased belching is rarely a symptom in isolation. Pathological acid exposure and hypomotility are associated with more SGB frequency. Whether SGB is a disordered response to other esophageal symptoms or their cause is unclear. [ABSTRACT FROM AUTHOR]

Little is known about the mucosal phenotype of the proximal human esophagus. There is evidence to suggest that the proximal esophagus is more sensitive to chemical and mechanical stimulation compared with the distal. This may have physiological relevance (e.g., in prevention of aspiration of gastroesophageal refluxate), but also pathological relevance (e.g., in reflux perception or dysphagia). Reasons for this increased sensitivity are unclear but may include impairment in mucosal barrier integrity or changes in sensory innervation. We assessed mucosal barrier integrity and afferent nerve distribution in the proximal and distal esophagus of healthy human volunteers. In 10 healthy volunteers baseline proximal and distal esophageal impedance was measured in vivo. Esophageal mucosal biopsies from the distal and proximal esophagus were taken, and baseline transepithelial electrical resistance (TER) was measured in Ussing chambers. Biopsies were examined immunohistochemically for presence and location of calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibers. In a further four healthy volunteers we investigated for colocalization of CGRP and protein gene product (PGP) 9.5 immunoreactivity in nerve fibers. Baseline impedance was higher in the proximal than in the distal esophagus [2,936 Ω (SD578) vs. 2,229 Ω (SD821); P = 0.03], however, baseline TER was not significantly different between them. Mucosal CGRP-immunoreactive nerves were found in the epithelium of both proximal and distal esophagus, but were located more superficially in the proximal mucosa compared with the distal [11.5 (SD7) vs. 21.7 (SD5) cell layers from lumen, P = 0.002] 19% of proximal, and 10% of distal mucosal PGP-immunoreactive fibers colocalized with CGRP. PGP-immunoreactive fibers were also significantly closer to the luminal surface in the proximal compared with the distal esophagus (P < 0.001). We conclude that mucosal barrier integrity is similar in proximal and distal esophagus, but proximal mucosal afferent nerves are in a more superficial location. The enhanced sensitivity to reflux-evoked symptoms of the proximal esophagus most likely has an anatomical basis. [ABSTRACT FROM AUTHOR]

Functional esophageal disorders are a group of disorders that cause esophageal symptoms, although with negative results on investigation with standard esophageal tests. Therefore, structural disorders, motility disorders with a histopathological basis and gastroesophageal reflux disease (GERD) are excluded. They are frequently encountered by clinicians, and so a systematic and evidence-based approach to investigation, diagnosis and treatment are crucial. There are four functional esophageal disorders defined by the ROME III consensus, namely functional heartburn, functional chest pain, functional dysphagia and globus. Since the advent of ROME, the specification of diagnostic criteria for functional esophageal disorders has allowed more comparable studies and clinical trials. Despite this, the evidence base for many therapies in use at present is not as robust as would be desired. In this paper, we discuss the four categories of functional esophageal disorders. We then propose diagnostic algorithms based on current evidence. Finally, we discuss current therapies for each of the four functional esophageal disorders based on current evidence. [ABSTRACT FROM AUTHOR]

This paper reports on the neurophysiology of the esophagus, including on the uneven distribution of innervation in the esophagus, reflected by the increased sensitivity and perception of gastroesophageal reflux disease (GERD) events in the proximal rather than distal esophagus; the role of the enteric nervous system (ENS) in swallowing; the role of the physiological stress-responsive systems, including the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal (HPA) axis in mediating esophageal pain; the advances in understanding pain mechanisms and brain structure provided by technological imaging advances; investigations into the efficacy of the descending-pain control system, including diffuse noxious inhibitory control (DNIC); the role of abnormal nervous signaling in afferent pathways in the pathogenesis of Barrett's esophagus (BE); and the contribution of the esophageal mucosa to reflux symptoms. [ABSTRACT FROM AUTHOR]

The development of the high-resolution esophageal manometry (HRM) and the Chicago classification have improved the diagnosis and management of esophageal motility disorders. However, some conditions have yet to be addressed by this classification. This review describes findings in HRM which are not included in the current Chicago classification based on the experience in our center. This includes the analysis of the upper esophageal sphincter, proximal esophagus, longitudinal muscle contraction, disorders related to gastroesophageal reflux disease and respiratory symptoms. The utility of provocative tests and the use of HRM in the evaluation of rumination syndrome and post-surgical patients will also be discussed. We believe that characterization of the manometric findings in these areas will eventually lead to incorporation of new criteria into the existing classification. [ABSTRACT FROM AUTHOR]

The pathogenesis of gastrointestinal reflux disease is multifactoral. Integral to the disease process is the refluxate itself. The characteristics and composition of the refluxate are dependent on several physiological variables. The refluxate may contain varying concentrations of acid, pepsin, gas, or contents of duodenal reflux (such as bile acid and pancreatic enzymes). Characteristics such as volume and proximal extent of the refluxate, and the chemical content of this refluxate can strongly influence the risk of symptom perception. Strong acid (pH<4) and duodeno-gastro-oesophageal reflux are also implicated in the development of mucosal damage in the form of oesophagitis, Barrett’s metaplasia and oesophageal adenocarcinoma. The manifestation of disease, however, is not entirely reliant on the refluxate, which must be considered in the context of the genetic, environmental and psychological susceptibility of the individual. [Copyright &y& Elsevier]

Background & Aims: Achalasia is treated with pneumatic dilation or Heller myotomy, but studies suggest poor long-term outcomes. We analyzed long-term outcomes after initial pneumatic dilation and studied factors associated with failure. Methods: A total of 209 patients (111 men; mean age, 51.2 ± 1.4 years) with achalasia who were treated with pneumatic dilation between 1992 and 2002 were followed. Outcomes were correlated with demographics, presenting symptoms, manometric features, and treatment variables by using χ2 and Student t tests. Results: All patients were initially treated with consecutive esophageal dilations up to balloon diameters of 3.0 (26%), 3.5 (41%), or 4.0 cm (33%). After dilations, mean lower esophageal sphincter (LES) pressure had decreased from 31.3 ± 1.3 to 14.0 ± 0.7 mm Hg (P < .0001); dysphagia decreased from 96% to 26%; and 49% had gained an average of 4.6 ± 0.5 kg (weight loss at presentation was 10.6 ± 0.7 kg in 39%). During follow-up, 66% required no additional treatment, whereas 23% underwent repeat dilations after 79 ± 8 months. Patients without recurrence were older (41.2 ± 2.1 vs 56.6 ± 1.6 years; P < .0001) and had lower post-treatment LES pressure (17.8 ± 1.2 vs 12.9 ± 0.6 mm Hg; P < .005). After 70-month follow-up, balloon dilation yielded good or excellent outcomes in 72% of patients. In nonresponders, rescue surgery yielded higher success rates than botulinum toxin therapy (84% vs 44%). Patient satisfaction ranged from good to excellent in 81% of patients. Conclusions: Treating achalasia with initial dilation and then surgery for short-term failures yielded good long-term results in more than 70% and treatment satisfaction in more than 80% of patients. Management of dilation failures is more problematic. [Copyright &y& Elsevier]

The current available methods for diagnosis of GORD are symptom questionnaires, catheter and wireless pH-metry, impedance-pH monitoring and Bilitec@. Osophageal pH monitoring allows both quantitative analysis of acid reflux and assessment of reflux-symptom association. Impedance-pH monitoring detects all types of reflux (acid and non-acid) and allows assessment of proximal extent of reflux, a relevant parameter for understanding symptoms perception and extraoesophageal symptoms. Bilitec provides a quantitative assessment of duodeno-gastro-oesophageal reflux. Oesophageal motor abnormalities have been associated with GORD symptoms as well as chest pain and dysphagia. High-resolution manometry contributed to re-classify oesphageal motor disorders. However, barium swallows are still essential for evaluation of oesophageal anatomy and combined oesophageal manometry-impedance can assess oesophageal motility and bolus transit simultaneously in a non-radiological way. Still in experimental phase, high-frequency ultrasound allows monitoring of the oesophageal wall thickness and exaggerated longitudinal muscle contraction that might be associated to chest pain and dysphagia. This chapter provides a critical evaluation of the clinical application of these techniques. [Copyright &y& Elsevier]

Esophageal mucosal dilated intercellular spaces (DIS) are frequently observed in patients with nonerosive reflux disease (NERD) and patients with esophagitis. The specificity of DIS is questionable, as it is present in up to 30% of asymptomatic healthy subjects and in patients with other esophageal disorders. DIS occurs in parallel with a drop in potential difference, diminished transepithelial resistance, and increased esophageal mucosal permeability. These alterations arise with exposure to acid and pepsin during gastroesophageal reflux, but the exact pathway of damage to the intercellular junctions remains unclear and seems to be multifactorial. Other noxious contents of the refluxate, such as bile acids, are harmful and DIS can also be induced by acute psychological stress. DIS can be assessed quantitatively with electron microscopy (EM), but it is also recognizable with light microscopy (LM). DIS can disappear after treatment with proton pump inhibitors (PPI); however, this is not the case in all NERD patients. A recent study showed that patients with NERD who are refractory to PPI might still have DIS; and animal experiments showed that persistence of DIS might be due to esophageal mucosal exposure to bile acids and/or psychological stress. In conclusion, DIS is a frequent but nonspecific histological feature of NERD. It can be caused by acid reflux, but bile acids in the refluxate and/or psychological stress can modulate the development or persistence of DIS. Although a causal relationship between DIS and heartburn has been proposed, it still needs to be proven and the underlying mechanisms investigated before considering DIS as a target for treatment of NERD. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Combined esophageal pH-impedance monitoring allows detection of nearly all gastroesophageal reflux episodes, acid as well as nonacid. However, the role of nonacid reflux in the pathogenesis of symptoms is poorly known. The aim of this study was to evaluate the diagnostic yield of this technique in patients with suspected reflux symptoms while on or off PPI therapy. PATIENTS AND METHODS: The recordings of 150 patients recruited at seven academic centers with symptoms possibly related to gastroesophageal reflux were analyzed. Reflux events were detected visually using impedance (Sandhill, CO) and then characterized by pHmetry as acid or nonacid reflux. The temporal relationship between symptoms and reflux episodes was analyzed: a symptom association probability (SAP) ≥95% was considered indicative of a positive association. RESULTS: One hundred fifty patients were included, 102 women (mean age 52 ± 14 yr, range 16–84). Among the 79 patients off PPI, five did not report any symptom during the recording period. A positive SAP was found in 41 of the 74 symptomatic patients (55.4%), including acid reflux in 23 (31.1%), nonacid reflux in three (4.1%), and acid and nonacid in 15 (20.3%). In the group of patients on PPI (N = 71, 46 women, mean age 51 ± 15 yr), 11 were asymptomatic during the study, SAP was positive in 22 of the 60 symptomatic patients (36.7%), including acid reflux in three (5.0%), nonacid reflux in 10 (16.7%), and acid and nonacid in nine (15.0%). The symptoms most frequently associated with nonacid reflux were regurgitation and cough. CONCLUSION: Adding impedance to pH monitoring improves the diagnostic yield and allows better symptom analysis than pHmetry alone, mainly in patients on PPI therapy. The impact of this improved diagnostic value on gastroesophageal reflux disease management remains to be investigated by outcome studies. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Proximal extent of gastroesophageal reflux (PER) is relevant for symptoms in GERD patients. It has been suggested that PER is determined by the volume of the refluxate that, in turn, might depend on the degree of gastric fullness. Abdominal straining, during ambulation, increases the likelihood of gastroesophageal reflux. We assessed the influence of gastric fullness and ambulation on proximal extent of reflux.METHODS: PER was assessed in 37 patients with GERD undergoing ambulatory pH impedance monitoring. In 14 controls and 19 GERD patients, esophageal pH impedance and gastric emptying were also studied simultaneously in stationary conditions. We compared PER during fasting, early postprandial (before half emptying), and late postprandial periods in ambulatory and stationary conditions.RESULTS: More reflux episodes reached the proximal esophagus in the postprandial period compared to fasting (60%± 4vs29%± 3,p<0.05). In stationary conditions, early postprandial reflux reached higher proximal extent than late postprandial reflux (15± 3%vs8± 4%,p<0.05). The proportion of reflux events reaching the proximal esophagus was significantly higher in ambulatory than in stationary conditions (29± 5%vs15± 3%,p<0.05).CONCLUSION: Compared to fasting, reflux episodes occurring after the meals are more likely to reach higher proximal extent, particularly so during the early postprandial period. The highest proportion of postprandial proximal reflux occurred in ambulatory condition. These findings suggest that reducing meal volumes and early postprandial physical activity might contribute to decrease proximal extent of reflux and postprandial GERD symptoms.(Am J Gastroenterol 2005;100:1–6) [ABSTRACT FROM AUTHOR]

Most of the factors involved in the pathogenesis of gastroesophageal reflux disease (GERD), previously described in European, Australian, and American studies, are present in Chinese patients with GERD, but at a lower scale. The acidity of gastric contents is reduced either spontaneously or by Helicobater pylon infection. A low-fat diet probably contributes to a more favorable gastric distribution of the meals, reduced obesity, and lowers the number of TLESRs. The prevalence of hiatal hernia is low and esophageal motility disorders are moderate. Like in Western countries, the pathophysiology of GERD in China is multifactorial, with variable combination of moderate abnormalities in individual patients, leading to milder forms of GERD. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Impedance monitoring is a new diagnostic method for gastroesophageal reflux disease (GERD) where multiple impedance electrode pairs are placed on a standard pH catheter. It detects reflux of a liquid and/or gas bolus into the esophagus, as well as its distribution, composition, and clearing. The aim of this collaborative study is to define normal values for 24-h ambulatory simultaneous impedance and pH monitoring (24-h Imp-pH), and compare bolus parameters by impedance monitoring to changes in[H+] measured by pH monitoring.METHODS: Sixty normal volunteers without GER symptoms underwent 24-h Imp-pH with impedance measured at six sites (centered at 3, 5, 7, 9, 15, and 17 cm above lower esophageal sphincter) and pH 5 cm above the LES. Reflux detected by impedance was characterized by the pH probe as either acid, weakly acidic, nonacid, or superimposed acid reflux. Proximal reflux was defined as reflux that reached the impedance site 15 cm above the LES.RESULTS: Reflux frequency was common upright (median-27, 25th and 75th quartile-16, 42), but rare recumbent (median-1; 0, 4). A median of 34% (14%, 49%) of upright reflux reached the proximal esophagus. There was a similar number of mixed composition (liquid+ gas; 49%) and liquid-only reflux (51%). Acid reflux was two-fold more common than weakly acidic reflux (p<0.001). Superimposed acid reflux and nonacid reflux were rare. Acid neutralization to pH 4 took twice as long as volume clearance measured by impedance.CONCLUSIONS: Combining impedance and pH monitoring improves the detection and characterization of GER. This study characterizes the frequency, duration, and extent of reflux in health and provides normal values for 24-h Imp-pH for future comparison with GERD patients. [ABSTRACT FROM AUTHOR]

Focuses on factors that trigger transient lower esophageal sphincter relaxations (TLESRs). Neurohormonal mechanisms controlling the triggering of TLESRs; Nonsurgical strategy used to improve the antireflux barrier in patients with reflux disease; Rate of TLESRs in patients with reflux disease and in healthy controls.

In patients with gastroesophageal reflux disease (GERD), transient lower esophageal sphincter relaxations (TLESRs) are more frequently accompanied by acid reflux than in normals. The role of esophageal tone during gastroesophageal reflux events is unknown. We studied the tonic motor activity in the body of the esophagus during TLESRs with and without acid reflux in 11 patients with erosive esophagitis and compared the results with those previously obtained in healthy subjects. Esophageal peristaltic contractions were recorded 13, 8, and 3 cm above a sleeve that measured LES pressure. An intraluminal balloon was inflated 8 cm above the sleeve to induce an esophageal tonic contraction [artificial high pressure zone (HPZ)]. The percentage of TLESRs with acid reflux was significantly higher in patients with esophagitis than in healthy controls (58.3% vs 37.3%, P < 0.05). TLESRs per se were not associated with an inhibition or increase in esophageal body contractility, which, however, changed substantially immediately after reflux. In patients with esophagitis the esophageal body tonic contractility was inhibited in 59.5% of TLESRs vs 36% in controls (P < 0.05). Esophageal contractions during TLESRs traveled down the esophagus in 77% of the instances in patients vs 96.5% in controls (P < 0.05). In conclusion, gastroesophageal reflux during TLESRs was more frequently associated with inhibition of esophageal body tonic contractility in patients with esophagitis than in normals. The different response of the esophageal body to reflux observed in GERD patients may partially contribute to the higher prevalence of reflux during TLESRs in these patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Meals increase the rate of transient lower esophageal sphincter (LBS) relaxations, in pail by gastric distension. The 5HT1 agonist sumatriptan reduces fasting fundic tone, prolongs the meal-induced fundic relaxation, and delays gastric emptying. We therefore hypothesized that sumatriptan might have a significant effect on the rate of postprandial transient LES relaxations and gastroesophageal reflux. We aimed to study the effect of sumatriptan on postprandial transient LES relaxations and reflux in healthy subjects. METHODS: Esophageal manometry and pH monitoring were performed in 13 healthy volunteers for 30 min before and 90 min after a semiliquid meal (790 kcal). Sumatriptan 6 mg subcutaneous (s.c.) or s.c. placebo were administered on separate days 30 min after the meal. RESULTS: Sumatriptan significantly increased postprandial LES pressure from 11.0 ± 1.2 mm Hg to 17.6 ± 1.2 mm Hg (p < 0.05). However, reflux events were not diminished. In the contrary, reflux was more frequent after sumatriptan than after placebo (3 [1.5-4.5]/30 min vs 2 [0-3]/30 min. p < 0.05). Transient LES relaxations were more frequent after sumatriptan. particularly in the second 30-min period after drug administration (3 [2.5-5]/30 min vs 2 [1.5-2]/30 min, p < 0.05). CONCLUSIONS: Sumatriptan prevents the natural decay in rate of transient LES relaxations that occurs after a meal and favors the occurrence of gastroesophageal reflux despite increasing LES pressure. The sustained postprandial high rate of transient LES relaxations after sumatriptan may be a consequence of a prolonged fundus relaxation and retention of meal in the proximal stomach. [ABSTRACT FROM AUTHOR]

The authors expresses their views concerning on the factors of non-erosive reflux disease (NERD) in the pathophysiology and its potential treatment for reflux disease. One of the author mentions the significance of trans-epithelial electrical resistance (TEER) in oesophageal mucosal barrier function. The other author also highlights the importance of impaired muscosal itntegrity.

A correction to the article "Assessment and Protection of Esophageal Mucosal Integrity in Patients With Heartburn Without Esophagitis" that was published in a previous issue of 2013 is presented.

The nadir esophageal pH of reflux observed during pH monitoring in the postprandial period is often more acidic than the concomitant intragastric pH. This paradox prompted the discovery of the 'acid pocket', an area of unbuffered gastric acid that accumulates in the proximal stomach after meals and serves as the reservoir for acid reflux in healthy individuals and gastroesophageal reflux disease (GERD) patients. However, there are differentiating features between these populations in the size and position of the acid pocket, with GERD patients predisposed to upward migration of the proximal margin onto the esophageal mucosa, particularly when supine. This upward migration of acid, sometimes referred to as an 'acid film', likely contributes to mucosal pathology in the region of the squamocolumnar junction. Furthermore, movement of the acid pocket itself to a supradiaphragmatic location with hiatus hernia increases the propensity for acid reflux by all conventional mechanisms. Consequently, the acid pocket is an attractive target for GERD therapy. It may be targeted in a global way with proton pump inhibitors that attenuate acid pocket development, or with alginate/antacid combinations that colocalize with the acid pocket and displace it distally, thereby demonstrating the potential for selective targeting of the acid pocket in GERD. [ABSTRACT FROM AUTHOR]

Abstract: Gastroesophageal reflux (GER) is one of the three most common causes of chronic unexplained cough. Diagnosing GER-related cough is challenging since many patients do not have esophagitis or an increased esophageal acid exposure during 24h esophageal pH-metry. A significant time association between acid reflux and cough can be demonstrated in a subgroup of patients, even if the total esophageal acid exposure is normal. Establishing an exact time relationship between reflux and cough requires objective measurements of both cough and reflux episodes. A variety of techniques for cough assessment are available, including sound recordings and continuous measurement of gastroesophageal pressures. The Symptom Association Probability (SAP) has been suggested as the most reliable algorithm to establish the non-chance association between GER and cough. Although the relationship between acid reflux and cough is generally accepted, the response rate of patients with chronic unexplained cough to proton pump inhibitor treatment (PPI) is poorer compared to that in patients with typical GERD symptoms. Combined impedance-pH recordings, a new technique for the measurement of all types of reflux, have recently shown that not only acid but also weakly acidic GER may be associated with cough. Moreover, measurements in patients “on” PPI therapy demonstrated that weakly acidic reflux may persist during PPI treatment and may be associated with cough. Aspiration of gastric contents into the lungs and a vagally mediated reflex arc, originating from the distal esophagus, have been proposed as pathophysiological mechanisms in GER-related cough. More recently, reflux induced bronchial hypersensitivity has been proposed as a third underlying mechanism. Treatment of GER-related cough remains challenging. So far, long term PPI treatments produce unsatisfactory results. In patients not responding to PPI, weakly acidic GER might still be the cause of cough. In these patients other therapeutic strategies i.e. abolishing all types of GER might need to be considered. Antireflux surgery has been performed successfully in a group of patients with GER-related cough. However, controlled, prospective outcome studies are necessary to confirm the role of antireflux treatments in the management of GER-related cough. [Copyright &y& Elsevier]

Background: Both gastroesophageal reflux and airway colonization with Pseudomonas aeruginosa (P aeruginosa) are common in lung transplantation (LTx) recipients. There is mounting evidence that, due to their interaction with the epithelium, both may be involved in chronic allograft dysfunction/bronchiolitis obliterans syndrome (BOS) after LTx. We investigated whether gastric aspiration and airway colonization with P aeruginosa after LTx are associated. Methods: In this retrospective, cross-sectional, case–control study, 24 stable double (SS) LTx recipients were included. Markers of gastroesophageal reflux (pepsin, bile acids) and airway inflammation (neutrophilia and interleukin-8 (IL-8)) were evaluated in bronchoalveolar lavage (BAL) samples of post-operatively colonized (n = 12) and non-colonized matched-control LTx recipients (n = 12). Results: BAL bile acid levels, but not pepsin levels, as well as neutrophilia and IL-8 protein levels were significantly elevated in colonized compared with non-colonized patients. Furthermore, bile acid levels, but not pepsin levels, correlated positively with BAL neutrophilia and IL-8 protein levels. Conclusions: Bile acid aspiration and airway colonization by P aeruginosa after LTx seem to be associated. This relationship between reflux and airway colonization and their role in the development of chronic allograft dysfunction/BOS after LTx should be further elucidated; nevertheless, induction of IL-8–mediated neutrophilic airway inflammation may be a putative mechanism. [Copyright &y& Elsevier]