Gastroesophageal reflux disease (GERD) is a prevalent comorbidity of chronic respiratory diseases including idiopathic pulmonary fibrosis (IPF), non-IPF interstitial lung disease, asthma, chronic obstructive pulmonary disease (COPD) and refractory chronic cough. Prevalence of symptoms of reflux and/ or refractory respiratory symptoms, along with concerns that refluxed gastric contents into the esophagus may micro-aspirate into the lungs causing injury and potentially accelerate disease progression, have resulted in high usage of empirical anti-reflux treatments. However, empirical treatment of reflux (medical or mechanical) is frequently ineffective without obvious explanation for the lack of respiratory improvement. This review provides novel and updated understanding of the pathophysiological mechanisms that link upper gut dysfunction, reflux (both distal and proximal), lung structure, lung mechanics and breathing patterns, including the potential role of the vagally mediated esophageal-bronchial reflex and the bi-directional nature of these interactions in individual respiratory diseases. We also highlight the need for a consensus between gastrointestinal and respiratory communities and propose a framework for diagnosing and managing GERD in respiratory disease.

BACKGROUND:Although patients with neurologic disorders commonly develop dysphagia, there remains little consensus on the role of initial esophagogastroduodenoscopy (EGD) or temporal guidance on gastrostomy placement. We aimed to characterize the predictors associated with EGD and gastrostomy recommendation at the initial gastroenterology consultation in patients with progressive neurologic disorders. METHODS:This retrospective study spanned from December 31, 2010, to December 31, 2021, and included patients with both dysphagia and neurologic disorders. Multivariate logistic regression determined the predictors for EGD and gastrostomy recommendation after the initial visit. RESULTS:Out of 273 patients, EGD was recommended for 163 (59.7%) at the initial evaluation. A diagnosis of amyotrophic lateral sclerosis (ALS) (odds ratio: 0.20; 95% confidence interval (CI): 0.07-0.52; P=0.001) and being referred by a neurologist (odds ratio: 0.37; 95% CI: 0.17-0.84; P<0.02) were the negative predictors of an initial EGD recommendation. Gastrostomy was recommended for 38 patients (13.9%) at the initial consultation. Dysphagia to both liquids and solids, body mass index, diagnosis of ALS, and clinical frailty scale scores were associated with gastrostomy (P≤0.01). A model of six variables had high predictive accuracy for EGD recommendation (area under the receiver operating characteristic curve: 0.7741). CONCLUSIONS:This study proposes a predictive model for initial EGD recommendation. We suggest that when considered in conjunction with the predictive clinical features of ALS diagnosis and dysphagia to both solids and liquids, the clinical frailty scale and American Society of Anesthesiologists physical status classification system scores may help clinicians anticipate gastrostomy when applied to patients with any neurologic disorder.

Eosinophilic esophagitis (EoE) is an increasingly common cause of food impaction. This study aims to provide a nationwide analysis of food impaction in patients with or without EoE diagnosis, concentrating on patient demographics, interventions, outcomes, and development of predictive machine-learning models. A retrospective assessment was conducted using Nationwide Emergency Department Sample data from January 1, 2018, to December 31, 2019. We compared patients with food impaction with an associated EoE diagnosis to those without EoE and derived machine-learning models to predict EoE using International Classification of Diseases codes at discharge for identification. Of 286,886,714 emergency department visits, 146,084 were for food impaction, with 7093 cases coinciding with an EoE diagnosis (4.9

Background and Aims:Gastroesophageal reflux (GER) is common and thought to contribute to disease progression in patients with respiratory disease. Delayed gastric emptying (DGE) can increase GER in patients with GER disease, but its effect in patients with respiratory disease, and how differing lung structure (eg, scarring, inflammation) and mechanics (eg, decreased thoracic pressure in restrictive disease, increased abdominal pressure in obstructive disease) influences this is unknown. Our aim was to understand these interrelationships and association with pulmonary function in patients with chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and non-IPF interstitial lung disease (non-IPF ILD). Methods:We prospectively recruited 22 COPD (aged 34-75 years), 33 IPF (45-74 years), and 19 non-IPF ILD (37-74 years) patients who underwent gastric emptying studies, high resolution impedance manometry, 24-hr pH-impedance, and pulmonary function testing, as part of routine lung transplantation assessment. Results:Gastric emptying was delayed in a total of 20(27%) patients; 5(23%) with COPD, 8(24%) with IPF and 7(37%) with non-IPF ILD. Notably, all 7 non-IPF ILD patients with DGE had nonspecific interstitial pneumonia (NSIP; ie, 70% of NSIP patients; P < .02 compared with other groups). DGE irrespective of disease type was not associated with increased acid exposure time, total bolus exposure time or number of reflux events. Furthermore, DGE was not associated with higher intra-abdominal pressure, specific esophageal dysmotility, or worse pulmonary function in any of the respiratory diseases. Conclusion:Significantly more NSIP patients have DGE compared with other respiratory diseases. Irrespective of this, DGE had little effect on GER or pulmonary function in any of the respiratory diseases.

INTRODUCTION:Gastroesophageal reflux is common in respiratory disease, but the interplay between gastrointestinal mechanisms that expose individuals to reflux and potentially aspiration, and lung mechanics and function remain incompletely understood. Our aim was to investigate this in patients with chronic obstructive pulmonary disease (COPD) and non-idiopathic pulmonary fibrosis (IPF) interstitial lung disease (non-IPF ILD), and compare with our published findings in IPF. METHODS:Fifty-seven patients with COPD (aged: 34-75 years) and 64 with non-IPF ILD (22-75 years) who underwent high-resolution impedance manometry and 24-hour pH impedance together with pulmonary function assessment were compared with 35 IPF patients (51-84 years). RESULTS:COPD patients were less likely to exhibit ineffective esophageal motility (IEM) and/or absent contractility ( P = 0.009; P = 0.028), and tended to exhibit esophagogastric junction outflow obstruction (EGJOO) and/or hypercontractility ( P = 0.09, P = 0.14) than IPF and non-IPF ILD patients. Notably, integrated relaxation pressure correlated with esophageal length index (ELI) ( P = 0.048) and inspiratory LESP ( P = 0.003), with latter 2 correlating with each other ( P < 0.001). EGJOO patients tended to have fewer proximal reflux events and reduced pulmonary function, with the latter inversely correlating with ELI ( P < 0.05). Non-IPF ILD patients were less likely to exhibit EGJOO than COPD patients ( P = 0.27), and less likely to exhibit IEM ( P = 0.07) than IPF patients. However, those with IEM or EGJOO exhibited greater proportions of reflux events reaching the proximal esophagus than those with normal motility ( P < 0.03), which in contrast to IPF, seemed not to associate with worse pulmonary function. DISCUSSION:Associations between esophageal motility, and lung mechanics and function, and consequently reflux, are very disease-specific.

Approximately 30% of patients with typical gastroesophageal reflux disease (GERD) symptoms have endoscopic evidence of erosive esophagitis (EE).1 The severity of EE is commonly graded using the Los Angeles (LA) classification system as grade A (minimal) to D (very severe), depending on the extent of endoscopically visible mucosal breaks (Supplementary Figure 1).2 Accurate grading of EE severity is crucial in clinical trials of medical EE treatments, as EE severity strongly influences both initial rates of healing and the likelihood of recurrence during maintenance treatment.3,4 Almost all EE treatment studies have relied exclusively on local investigators' grading of EE severity to determine study eligibility and response to treatment. Those few studies that included central adjudication did not assess the reliability of grading by local investigators.5 Unlike typical studies of EE treatment, the phase III clinical trial of vonoprazan versus lansoprazole for the treatment of EE (NCT04124926) mandated central adjudication of endoscopic grading for study participation.6 The aim of the present investigation was to evaluate the rate of agreement between local investigators and central adjudicators for EE grading during screening for entrance into that clinical trial.

BACKGROUND:For many patients with lung disease the only proven intervention to improve survival and quality of life is lung transplantation (LTx). Esophageal dysmotility and gastroesophageal reflux (GER) are common in patients with respiratory disease, and often associate with worse prognosis following LTx. Which, if any patients, should be excluded from LTx based on esophageal concerns remains unclear. Our aim was to understand the effect of LTx on esophageal motility diagnosis and examine how this and the other physiological and mechanical factors relate to GER and clearance of boluses swallowed.METHODS:We prospectively recruited 62 patients with restrictive (RLD) and obstructive (OLD) lung disease (aged 33-75 years; 42 men) who underwent high resolution impedance manometry and 24-h pH-impedance before and after LTx.KEY RESULTS:RLD patients with normal motility were more likely to remain normal (p = 0.02), or if having abnormal motility to change to normal (p = 0.07) post-LTx than OLD patients. Esophageal length (EL) was greater in OLD than RLD patients' pre-LTx (p < 0.001), reducing only in OLD patients' post-LTx (p = 0.02). Reduced EL post-LTx associated with greater contractile reserve (r = 0.735; p = 0.01) and increased likelihood of motility normalization (p = 0.10). Clearance of reflux improved (p = 0.01) and associated with increased mean nocturnal baseline impedance (p < 0.001) in RLD but not OLD. Peristaltic breaks and thoraco-abdominal pressure gradient impact both esophageal clearance of reflux and boluses swallowed (p < 0.05).CONCLUSIONS AND INFERENCES:RLD patients are more likely to show improvement in esophageal motility than OLD patients post-LTx. However, the effect on GER is more difficult to predict and requires other GI, anatomical and pulmonary factors to be taken into consideration.

BACKGROUND:Patients with erosive oesophagitis, and those with persistent symptomatic non-erosive gastro-oesophageal reflux disease, require long-term maintenance treatment with acid-suppressing agents. AIM:To evaluate the safety of vonoprazan, a potassium-competitive acid blocker, in an integrated analysis of data from clinical trials in adults. METHODS:We included 14 clinical trials of vonoprazan conducted in multiple countries. Mean duration of exposure in person-years to vonoprazan (n = 5318) was 2068, to comparators lansoprazole (n = 1925) or esomeprazole (n = 86) was 751, and to placebo (n = 779) was 59. We report adverse events, serum gastrin, and liver enzyme levels as the main outcomes. Post-marketing safety data from December 26, 2014 (date of commercialisation in Japan) to December 25, 2023, are also provided. RESULTS:Nasopharyngitis was the only adverse event reported by at least 5.0% of patients (6.94% vonoprazan, 5.07% proton pump inhibitor (PPI), 4.49% placebo). Incidence rates per 100 person-years for serious adverse events were 10.39 for vonoprazan, 10.65 for PPIs, and 1.69 for placebo. One patient each on vonoprazan and lansoprazole was diagnosed with gastric cancer. Mean serum gastrin levels were higher on vonoprazan than lansoprazole but normalised by 4 weeks after discontinuation. Elevated liver enzyme levels were infrequent and of low magnitude with no differences between vonoprazan and PPIs. There were four deaths; none was considered related to study drug. CONCLUSIONS:Vonoprazan was well tolerated. Its safety profile from both clinical trial and post-marketing data were consistent and comparable to that of its PPI comparators with respect to treatment-emergent adverse events.

Introduction: Esophageal dysmotility and gastroesophageal reflux (GER) are common in respiratory disease and following lung transplant (LTx), and predict worse pulmonary function and disease progression. Timing and significance of testing for esophageal disease in these patients remain unclear. The aim of this study was to examine the changes in esophageal motor function (Chicago Classification v4.0) following LTx and association with GER in patients with restrictive (RLD) or obstructive (OLD) lung disease. Methods: High resolution impedance esophageal manometry (HRIM) and 24hr impedance-pH (MII-pH) was performed in 57 respiratory patients (40 restrictive, 17 obstructive) before and after LTx (mean age 60 yrs (range 33-75 yrs), 39 males) between November 2016 and October 2022. Results: RLD: Before LTx, 15(38%) exhibited abnormal motility; the majority ineffective esophageal motility (IEM)(8,53%) or esophagogastric junction outflow obstruction (EGJOO)(6,40%). 1 had distal esophageal spasm and the rest were (25,63%) normal. Following LTx, 21(53%) retained the same diagnosis as pre-LTx. Patients with normal motility pre-LTx were more likely to retain the same diagnosis post-LTx (17/25, 68%) than those with abnormal motility (4/15,27%)(P=0.021), particularly EGJOO(1/6, 17%)(P=0.059). 9 of 15 (60%) with abnormal motility pre-LTx changed to normal post-LTx. OLD: Before LTx, 8(47%) exhibited abnormal motility, with the majority EGJOO (4,50%). The rest had IEM (2,25%), absent motility (1,12.5%) or hypercontractility (1,12.5%). 9 (53%) exhibited normal motility. Following LTx 10 (59%) retained the same diagnoses, but those with normal motility (5/9,56%) were no more likely to retain the same diagnoses as those with abnormal motility (5/8,63%). 1 of 8 (12.5%) with abnormal motility changed to normal post-LTx, which is lower than seen in RLD(P=0.07). pH findings revealed that although acid exposure time (AET) was similar pre-LTx (RLD 2.4(0.7-7.0) v OLD 2.0(0.5-3.4); P=0.53), there was a decrease in AET in RLD (1.7(0.3-3.5);P=0.05) but no change in OLD (3.7(0.6-10.1);P=0.31) post-LTx. Conclusion: 1. Testing prior to LTx guides therapy pre-and peri-LTx but does not predict post-LTx physiology. 2. Post-LTx testing is frequently different from pre-LTx testing and may guide long-term therapy. 3. Motility in RLD is more likely to remain normal or change to normal post-LTx than in OLD, and appears to predict improved AET.