BACKGROUND: Defecation dysfunction may contribute to chronic constipation (CC), but the impact of obesity on anorectal physiology in CC remains unclear. We aimed to evaluate the relationship between obesity and anorectal function on physiologic testing in patients presenting with CC.

METHODS: This was a retrospective cohort study of consecutive adults who underwent high resolution anorectal manometry (HRAM) at a tertiary center for CC. Patient demographics, clinical history, surgical/obstetric history, medications, and HRAM results were reviewed. Patients were classified into obese (BMI > 30 kg/m2) vs non-obese (BMI < 30 kg/m2) groups at the time of HRAM. Fisher-exact/student t-test for univariate analyses and general linear regression for multivariable analysis were performed.

RESULTS: 383 adults (mean 50.3 years; 85.8% female) with CC were included. On HRAM, patients with obesity had lower anal sphincter resting tone (37.3 vs 48.5 mmHg, p = 0.005) and maximum squeeze pressure (104.8 mmHg vs 120.0 mmHg, p = 0.043). No significant differences in dyssynergia (61% vs 53%, p = 0.294) and failed balloon expulsion (18% vs 25%, p = 0.381) were found between obese and non-obese groups. On balloon distention testing, the maximum tolerated (163.5 vs 147.6 mL, p = 0.042) and urge sensation (113.9 vs 103.7 mL, p = 0.048) volumes were significantly increased among patients with obesity. After adjusting for potential confounders, obesity remained independently associated with increased maximum tolerated volume (β-coefficient 13.7, p = 0.049).

CONCLUSION: Obesity was independently associated with altered rectal sensitivity among patients with CC. Altered rectal sensation may play an important role in CC among patients with obesity. Anorectal physiology testing should be considered to understand the pathophysiology and guide management.

GOALS: To assess the predictive value of baseline peripheral absolute eosinophil counts (AECs) for proton pump inhibitor (PPI) response in eosinophilic esophagitis (EoE).

BACKGROUND: PPI leads to histologic remission in  50% of EoE patients, although there are few distinguishing clinical features between PPI-responsive (PPI-r-EoE) and nonresponsive (PPI-nr-EoE) diseases. Peripheral eosinophilia is present in  50% of EoE cases and is associated with eosinophil density on esophageal biopsy and worse clinical outcomes. The association between peripheral eosinophilia and PPI-responsiveness in EoE remains unclear.

STUDY: This is a retrospective cohort study of adult EoE patients at a tertiary center between 2012 and 2016. All patients underwent twice daily PPI trials for ≥8 weeks followed by repeat esophageal biopsies and were classified as PPI-r-EoE or PPI-nr-EoE based on histologic response (<15 eosinophils/high power field). Baseline peripheral AEC was obtained within 1 month before index endoscopy. Analyses were performed using Fisher exact/Student t test (univariate) and logistic regression (multivariable).

RESULTS: One hundred eighty-three patients (91 PPI-nr-EoE and 92 PPI-r-EoE) were included. Mean peripheral AEC was higher among PPI-nr-EoE patients (0.41 vs 0.24 K/µL, P = 0.013). Baseline peripheral eosinophilia (>0.5 K/µL) was more prevalent among patients with PPI-nr-EoE (70.4% vs 45.5%, P = 0.023) and a history of food impaction (51.9% vs 23.7%, P = 0.0082). On multivariable analyses, peripheral eosinophilia remained an independent predictor for PPI response (adjacent odds ratio = 2.86, CI: 1.07-7.62, P = 0.036) and food impaction (adjacent odds ratio = 2.80, CI: 1.07-7.35, P = 0.037).

CONCLUSIONS: Baseline peripheral eosinophilia independently predicts PPI nonresponse and food impaction in EoE patients. Peripheral AEC may help therapy selection in EoE and prevent delays in achieving histologic remission.

INTRODUCTION: Anorectal function testing is traditionally relegated to subspecialty centers. Yet, it is an office-based procedure that appears capable of triaging care for the many patients with Rome IV functional constipation that fail empiric over-the-counter therapy in general gastroenterology, as an alternative to empirical prescription drugs. We aimed to evaluate cost-effectiveness of routine anorectal function testing in this specific population.

METHODS: We performed a cost-effectiveness analysis from the patient perspective and a cost-minimization analysis from the insurer perspective to compare 3 strategies: (i) empiric prescription drugs followed by pelvic floor physical therapy (PFPT) for drug failure, (ii) empiric PFPT followed by prescription drugs for PFPT failure, or (iii) care directed by up-front anorectal function testing. Model inputs were derived from systematic reviews of prospective clinical trials, national cost data sets, and observational cohort studies of the impact of chronic constipation on health outcomes, healthcare costs, and work productivity.

RESULTS: The most cost-effective strategy was upfront anorectal function testing to triage patients to appropriate therapy, in which the subset of patients without anal hypocontractility on anorectal manometry and with a balloon expulsion time of at least 6.5 seconds would be referred to PFPT. In sensitivity analysis, empiric PFPT was more cost effective than empiric prescription drugs except for situations in which the primary goal of treatment was to increase bowel movement frequency. If adopted, gastroenterologists would refer ∼17 patients per year to PFPT, supporting feasibility.

DISCUSSION: Anorectal function testing seems to be an emergent technology to optimize cost-effective outcomes, overcoming testing costs by phenotyping care.

INTRODUCTION: Guidelines advise esophageal motility testing for dysphagia when structural disorders are ruled out, but cost concerns impede adoption. We evaluated cost-effective positioning of esophageal motility testing in the algorithm to evaluate esophageal dysphagia.

METHODS: We developed a decision analytic model comparing 3 strategies: (i) esophageal manometry, (ii) screening impedance planimetry followed by esophageal manometry if needed, or (iii) nonalgorithmic usual care. Diagnostic test accuracy was adapted to expected rates of esophageal motility disorders in general gastroenterology populations. We modeled routine testing for all patients with nonstructural/mechanical dysphagia compared with selective testing with strong suspicion for achalasia. Cost outcomes were defined on national commercial and Medicare datasets stratified on age and sex. Health outcomes were modeled on populations with achalasia. The time horizon was 1 year.

RESULTS: Motility testing was preferred over nonalgorithmic usual care due to cost savings rather than health gains. To commercial insurers, routine esophageal manometry for nonstructural/mechanical dysphagia would be cost-saving below a reimbursed cost of $2,415. Screening impedance planimetry would be cost saving below a reimbursed cost of $1,130. The limit for reimbursed costs would be lower for patients older than 65 years to achieve cost savings mainly due to insurance. Sex did not significantly influence cost-effectiveness. Patients and insurers preferred routine screening impedance planimetry before manometry when the index of suspicion for achalasia was below 6%.

DISCUSSION: Aligning with practice guidelines, routine esophageal motility testing seems cost saving to patients and insurers compared with nonalgorithmic usual care to evaluate nonstructural/mechanical dysphagia. Choice of testing should be guided by index of suspicion.

BACKGROUND: Patients with obesity often report esophageal symptoms, with abnormal reflux and esophageal motility suggested as potential mechanisms. However, prior studies showed varying results, often limited by study design/size and esophageal function/symptom measures utilized. We aimed to examine the relationship between obesity and objective esophageal function testing and patient-reported outcomes, utilizing prospective symptom, manometric and reflux monitoring data with impedance.

METHODS: Adults referred for high-resolution impedance-manometry (HRiM) and multichannel intraluminal impedance-pH monitoring (MII-pH) to evaluate esophageal symptoms were enrolled. Validated symptom and health-related quality of life (HR-QOL) instruments were prospectively collected: GERDQ, reflux symptoms index (RSI), dominant symptom intensity (DSI, multiplied 5-point Likert scales for symptom frequency/severity), global symptom severity (GSS, 100-point visual analog scale), and Short Form-12 (SF-12) for HR-QOL. Esophageal function testing measures were compared across body mass index (BMI) categories and correlated with patient-reported outcomes.

KEY RESULTS: Seven hundred and fifty four patients were included (Normal:281/Overweight:253/Class I obesity:137/Class II/III obesity:83). Reflux burden measures on MII-pH (acid exposure time, total reflux episodes, bolus exposure time), conclusive pathologic reflux (Lyon), and hiatal hernia were increased in higher obesity classes compared to normal BMI. Class II/III obesity was associated with more normal/hypercontractile swallows, less ineffective swallows, and better bolus transit on HRiM. BMI correlated positively with GERDQ/RSI/DSI/GSS, and negatively with physical component score (SF-12). Esophageal symptom severity and HR-QOL correlated strongly with MII-pH findings, but not HRiM measures.

CONCLUSIONS/INFERENCES: Obesity is associated with increased esophageal symptom burden and worse physical HR-QOL, which correlate with higher acid/bolus reflux burden but not altered esophageal motility/transit/contractile reserve.

INTRODUCTION: Gastroesophageal reflux disease has been associated with worse lung transplant outcomes. We aimed to assess local practices for esophageal function testing (EFT) across transplant centers.

METHODS: This was a survey study of all United Network for Organ Sharing-accredited adult lung transplant centers regarding local EFT practice.

RESULTS: Among 39/63 (60%) responded centers, 38.5% required any EFT (35.9% esophageal manometry, 15.4% pH monitoring, and 28.2% pH impedance), while another 28.2% may consider EFT based on symptoms. Five-year transplant volume was higher among centers requiring EFT (253 vs 159, P = 0.04).

DISCUSSION: Only a minority of lung transplant centers routinely obtained EFT, supporting the need for guidelines for standardized reflux/esophageal assessment.

INTRODUCTION: An association between gastroesophageal reflux disease (GERD) and common psychiatric conditions, most notably anxiety and depression, has been reported. However, the magnitude of this association is poorly understood. Therefore, we aimed to systematically assess this issue.

METHODS: We comprehensively searched multiple bibliographic databases (Embase, PubMed, Scopus, and Web of Science) from inception to May 15, 2023. We retrieved observational studies that reported the prevalence of anxiety and/or depressive symptoms diagnosed by validated questionnaires in ≥100 adults (aged 18 years or older) with GERD. We also included cohort studies that explored the risk of incident GERD in subjects with anxiety/depression vice versa scenario. Finally, we included Mendelian randomization studies that assessed the cause-and-effect relationship between anxiety/depression and GERD. The extracted data were combined using a random-effects model.

RESULTS: In total, 36 eligible studies were included. The pooled prevalences of anxiety and depressive symptoms were 34.4% (95% confidence interval [CI] 24.7-44.2; I2 = 99.4%) and 24.2% (95% CI 19.9-28.5; I2 = 98.8%) in subjects with GERD based on 30 studies, respectively. Both anxiety and depressive symptoms were more common in subjects with GERD compared with those in healthy controls (odds ratio = 4.46 [95% CI 1.94-10.25] and odds ratio = 2.56 [95% CI 1.11-5.87], respectively). According to 3 cohort studies, subjects with GERD were at an increased risk of developing anxiety/depression and vice versa. Finally, 3 Mendelian randomization studies showed that genetic liability to these mood disorders is linked to an increased risk of developing GERD and vice versa.

DISCUSSION: Up to 1 in 3 subjects with GERD experience anxiety and depression. There is likely a bidirectional causal relationship between anxiety/depression and GERD.

BACKGROUND AND AIM: Gastroesophageal reflux has been associated with idiopathic pulmonary fibrosis (IPF), although the directionality of the relationship has been debated. Data on the value of objective reflux measures in predicting IPF disease progression and mortality remain limited. We aimed to evaluate the association between multichannel intraluminal impedance and pH testing (MII-pH) and 3-year pulmonary outcomes in IPF patients.

METHODS: This was a retrospective cohort study of adults with IPF who underwent pre-lung transplant MII-pH off acid suppression at a tertiary center. Patients were followed for 3 years after MII-pH for poor pulmonary outcomes (hospitalization for respiratory exacerbation or death). A secondary analysis was performed using mortality as outcome of interest. Time-to-event analyses using Kaplan-Meier and Cox regression were performed to evaluate associations between MII-pH and poor outcomes.

RESULTS: One hundred twenty-four subjects (mean age = 61.7 ± 8 years, 62% male) were included. Increased bolus exposure time (BET) on MII-pH was associated with decreased time to poor pulmonary outcomes and death (log-ranked P-value = 0.017 and 0.031, respectively). On multivariable Cox regression analyses controlling for potential confounders including age, sex, smoking history, body mass index, proton pump inhibitor use, baseline pulmonary function, and anti-fibrotic therapy, increased BET was an independent predictor for poor pulmonary outcomes [hazard ratio 3.18 (95% confidence interval: 1.25-8.09), P = 0.015] and mortality [hazard ratio 11.3 (95% confidence interval: 1.37-63.9), P = 0.025] over 3 years.

CONCLUSIONS: Increased BET on MII-pH is an independent predictor of poor pulmonary outcomes and mortality over 3 years in IPF patients. These findings also support a role for gastroesophageal reflux in IPF disease progression and the potential impact of routine reflux testing and treatment.