Yadlapati R, Kaizer AM, Sikavi DR, et al. Distinct Clinical Physiologic Phenotypes of Patients With Laryngeal Symptoms Referred for Reflux Evaluation. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2022;20(4):776-786.e1. doi:10.1016/j.cgh.2021.05.025

BACKGROUND & AIMS: Heterogeneous presentations and disease mechanisms among patients with laryngeal symptoms account for misdiagnosis of laryngopharyngeal reflux (LPR), variations in testing, and suboptimal outcomes. We aimed to derive phenotypes of patients with laryngeal symptoms based on clinical and physiologic data and to compare characteristics across phenotypes.

METHODS: A total of 302 adult patients with chronic laryngeal symptoms were prospectively enrolled at 3 centers between January 2018 to October 2020 (age 57.2 ± 15.2 years; 30% male; body mass index 27.2 ± 6.0 kg/m2). Discriminant analysis of principal components (DAPC) was applied to 12 clinical and 11 physiologic variables collected in stable condition to derive phenotypic groups.

RESULTS: DAPC identified 5 groups, with significant differences across symptoms, hiatal hernia size, and number of reflux events (P < .01). Group A had the greatest hiatal hernia size (3.1 ± 1.0 cm; P < .001) and reflux events (37.5 ± 51; P < .001), with frequent cough, laryngeal symptoms, heartburn, and regurgitation. Group B had the highest body mass index (28.2 ± 4.6 kg/m2; P < .001) and salivary pepsin (150 ± 157 ng/mL; P = .03), with frequent cough, laryngeal symptoms, globus, heartburn, and regurgitation. Group C frequently reported laryngeal symptoms (93%; P < .001), and had fewest esophageal symptoms (9.6%; P < .001) and reflux events (10.7 ± 11.0; P < .001). Group D commonly reported cough (88%; P < .001) and heartburn. Group E (18%) was oldest (62.9 ± 14.3 years; P < .001) and distinguished by highest integrated relaxation pressure.

CONCLUSIONS: DAPC identified distinct clinicophysiologic phenotypes of patients with laryngeal symptoms referred for reflux evaluation: group A, LPR and gastroesophageal reflux disease (GERD) with hiatal hernia; group B, mild LPR/GERD; group C, no LPR/No GERD; group D, reflex cough; and group E, mixed/possible obstructive esophagogastric junction. Phenotypic differences may inform targeted clinical trials design and improve outcomes.

McCarty TR, Chouairi F, Hathorn KE, Chan WW, Thompson CC. Trends and Socioeconomic Health Outcomes of Cannabis Use Among Patients With Gastroparesis: A United States Nationwide Inpatient Sample Analysis. Journal of clinical gastroenterology. 2022;56(4):324-330. doi:10.1097/MCG.0000000000001526

BACKGROUND: Although cannabis may worsen nausea and vomiting for patients with gastroparesis, it may also be an effective treatment for gastroparesis-related abdominal pain. Given conflicting data and a lack of current epidemiological evidence, we aimed to investigate the association of cannabis use on relevant clinical outcomes among hospitalized patients with gastroparesis.

MATERIALS AND METHODS: Patients with a diagnosis of gastroparesis were reviewed from the National Inpatient Sample (NIS) database between 2008 and 2014. Gastroparesis was identified by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes with patients classified based on a diagnosis of cannabis use disorder. Demographics, comorbidities, socioeconomic status, and outcomes were compared between cohorts using χ2 and analysis of variance. Logistic regression was then performed and annual trends also evaluated.

RESULTS: A total of 1,473,363 patients with gastroparesis were analyzed [n=33,085 (2.25%) of patients with concomitant cannabis use disorder]. Patients with gastroparesis and cannabis use disorder were more likely to be younger and male gender compared with nonusers (36.7±18.8 vs. 51.9±16.8; P<0.001 and 52.9% vs. 33.5%; P<0.001, respectively). Race/ethnicity was different between groups (P<0.001). Cannabis users had a lower median household income and were more likely to have Medicaid payor status (all P<0.001). Controlling for confounders, length of stay, and mortality were significantly decreased for patients with gastroparesis and cannabis use (all P<0.001).

CONCLUSION: While patients with gastroparesis and cannabis use disorder were younger, with a lower socioeconomic status, and disproportionately affected by psychiatric diagnoses, these patients had better hospitalization outcomes, including decreased length of stay and improved in-hospital mortality.

Rangan V, Borges LF, Lo WK, et al. Novel Advanced Impedance Metrics on Impedance-pH Testing Predict Lung Function Decline in Idiopathic Pulmonary Fibrosis. The American journal of gastroenterology. 2022;117(3):405-412. doi:10.14309/ajg.0000000000001577

INTRODUCTION: Gastroesophageal reflux has been associated with idiopathic pulmonary fibrosis (IPF). Mean nocturnal baseline impedance (MNBI) is a marker of esophageal mucosal integrity, whereas postreflux swallow-induced peristaltic wave (PSPW) index reflects esophageal chemical clearance. Both metrics offer novel ways to assess reflux burden on multichannel intraluminal impedance-pH testing (MII-pH), but their role in extraesophageal reflux remains unclear. We aimed to evaluate the relationship between these novel metrics and lung function decline in patients with IPF.

METHODS: Adults with IPF undergoing prelung transplant MII-pH were enrolled. All patients completed pulmonary function testing (PFT) at the time of MII-pH and at the 1-year follow-up. MNBI was calculated by averaging baseline impedance at three 10-minute intervals (1 AM/2 AM/3 AM). PSPW index was the proportion of all reflux episodes, followed by a peristaltic swallow within 30 seconds. Univariate (Student t-test/Pearson correlation) and multivariable (general linear regression) analyses were performed.

RESULTS: One hundred twenty-five subjects (mean age = 61.7 years, 62% men) were included. Forced expiratory volume in one second and forced vital capacity declined more significantly over 12 months in subjects with lower distal MNBI, proximal MNBI, and PSPW index (all P < 0.05). On multivariable analyses adjusting for age, sex, proton pump inhibitor use, and baseline lung function, distal MNBI (β = -10.86, P = 0.024; β = -8.03, P = 0.045), proximal MNBI (β = -13.5, P = 0.0068; β = -9.80, P = 0.025), and PSPW index (β = -18.1, P = 0.010; β = -12.55, P = 0.050) remained predictive of greater forced expiratory volume in one second and forced vital capacity decline.

DISCUSSION: Low distal MNBI, proximal MNBI, and PSPW index independently predicted more severe lung function decline over 1 year in patients with IPF. These impedance metrics may have prognostic value and support a role for reflux in IPF pathogenesis.

Cai JX, Wong D, Lee DJH, Chan WW. Eating and Psychiatric Disorders Are Independent Risk Factors for Rumination Syndrome. Journal of clinical gastroenterology. 2022;56(3):228-233. doi:10.1097/MCG.0000000000001510

GOAL: The goal of this study was to evaluate whether a history of eating disorders (EDs) or psychiatric disorders (PDs) are risk factors for rumination syndrome (RS).

BACKGROUND: RS is a disorder of gut-brain interaction characterized by an effortless postprandial retrograde flow of ingested contents. Disorder of gut-brain interactions have been associated with psychiatric and behavioral comorbidities. No prior comparative study has assessed the relationship between RS and ED or PD.

METHODS: This was a case-control study of adults with RS at a tertiary center in January 2013 to January 2018. Two age-matched/gender-matched controls per RS case were identified. The Fisher exact test (categorical)/Student t test (continuous) and forward stepwise logistic regression were performed for univariate and multivariable analyses, respectively.

RESULTS: Seventy-two patients (24 cases/48 controls) were included. Baseline demographics and characteristics were similar between cases and controls. Among RS patients, 9 (37.5%) had a history of ED, including 3 (12.5%) anorexia nervosa and 4 (16.7%) bulimia nervosa; and 20 (83.3%) had a PD, including 9 (37.5%) anxiety and 7 (29.2%) depression. Prevalence of ED (37.5% vs. 4.2%, P=0.0002) and PD (83.3% vs. 50.0%, P=0.0062) were higher among RS patients than controls. Specifically, the risks of anorexia nervosa (16.7% vs. 0%, P=0.005) and bulimia nervosa (21.1% vs. 0%, P=0.001) were both increased in RS patients. On multivariable analysis, ED (adjusted odds ratio=16.4, P=0.0033) and PD (adjusted odds ratio=4.47, P=0.029) remained independent predictors for RS.

CONCLUSIONS: A history of ED and PD were independent risk factors for RS. Abnormal eating behaviors and psychiatric comorbidities may contribute to the pathogenesis of RS. Evaluation of RS should include a detailed history for ED and PD.

Derousseau T, Chan WW, Cangemi D, Kaza V, Lo WK, Gavini S. Delayed Gastric Emptying in Prelung Transplant Patients Is Associated With Posttransplant Acute Cellular Rejection Independent of Reflux. Journal of clinical gastroenterology. 2022;56(2):e121-e125. doi:10.1097/MCG.0000000000001502

GOAL: The goal of this study was to evaluate the relationship between pretransplant delayed gastric emptying (DGE) and posttransplant acute cellular rejection (ACR) in lung transplant recipients.

BACKGROUND: DGE is very prevalent (23% to 91%) after lung transplantation but pretransplant prevalence has not been well studied. DGE may lead to poor posttransplant outcomes by predisposing to microaspiration. Pretransplant testing for DGE may help identify patients at risk for negative posttransplant outcomes including ACR.

MATERIALS AND METHODS: A retrospective review of a prospectively collected database of consecutive patients undergoing prelung transplant evaluation at a tertiary referral center from 2010 to 2015 was performed. Patients with pretransplant gastric emptying scintigraphy were included in the study. ACR diagnosis was made using International Society for Heart and Lung Transplantation (ISHLT) histologic criteria. Typical gastroparesis symptoms at the time of gastric emptying scintigraphy and pretransplant 24-hour pH impedance monitoring (MII-pH) data was collected. Logistic regression was used for multivariate analysis. Subgroup analyses were performed to account for gastroesophageal reflux (GER).

RESULTS: A total of 83 subjects (18 with DGE, 51.8% male, mean age: 53.6 y) met the criteria for inclusion. Patients with DGE were more likely to have typical symptoms of gastroparesis, though 61.1% of DGE patients were asymptomatic. ACR was more prevalent in patients with DGE (33.3% vs. 12.3%, P=0.04). This correlation was independent of GER as measured by MII-pH on subgroup analysis (75% vs. 14.3%, n=0.02).

DISCUSSION: Lung transplant recipients with pretransplant DGE have a higher incidence of ACR, independent of GER. Routine pretransplant testing for DGE may help identify patients at greater risk for adverse posttransplant outcomes as the majority of patients with DGE are asymptomatic.


Shah ED, Staller K, Nee J, et al. Evaluating the Impact of Cost on the Treatment Algorithm for Chronic Idiopathic Constipation: Cost-Effectiveness Analysis. The American journal of gastroenterology. 2021;116(10):2118-2127. doi:10.14309/ajg.0000000000001403

INTRODUCTION: Chronic idiopathic constipation (CIC) is a common and burdensome illness. We performed a cost-effectiveness analysis of the US Food and Drug Administration-approved CIC drugs to evaluate and quantify treatment preferences compared with usual care from insurer and patient perspectives.

METHODS: We evaluated the subset of patients with CIC and documented failure of over-the-counter (OTC) osmotic or bulk-forming laxatives. A RAND/UCLA consensus panel of 8 neurogastroenterologists informed model design. Treatment outcomes and costs were defined using integrated analyses of registered clinical trials and the US Centers for Medicare and Medicaid Services-supported cost databases. Quality-adjusted life years (QALYs) were calculated using health utilities derived from clinical trials. A 12-week time horizon was used.

RESULTS: With continued OTC laxatives, CIC-related costs were $569 from an insurer perspective compared with $3,154 from a patient perspective (considering lost wages and out-of-pocket expenses). CIC prescription drugs increased insurer costs by $618-$1,015 but decreased patient costs by $327-$1,117. Effectiveness of CIC drugs was similar (0.02 QALY gained/12 weeks or ∼7 healthy days gained/year). From an insurer perspective, prescription drugs (linaclotide, prucalopride, and plecanatide) seemed less cost-effective than continued OTC laxatives (incremental cost-effectiveness ratio >$150,000/QALY gained). From a patient perspective, the cost-effective algorithm started with plecanatide, followed by choosing between prucalopride and linaclotide starting at the 145-μg dose (favoring prucalopride among patients whose disease affects their work productivity). The patient perspective was driven by drug tolerability and treatment effects on quality of life.

DISCUSSION: Addressing costs at a policy level has the potential to enable patients and clinicians to move from navigating barriers in treatment access toward truly optimizing treatment choice.

Sikavi DR, Cai JX, Leung R, Carroll TL, Chan WW. Impaired Proximal Esophageal Contractility Predicts Pharyngeal Reflux in Patients With Laryngopharyngeal Reflux Symptoms. Clinical and translational gastroenterology. 2021;12(10):e00408. doi:10.14309/ctg.0000000000000408

OBJECTIVES: The pathophysiology of laryngopharyngeal reflux (LPR) remains incompletely understood. Proximal esophageal motor dysfunction may impair bolus clearance, increasing the risk of pharyngeal refluxate exposure. We aimed to evaluate the association of proximal esophageal contractility with objective reflux metrics.

METHODS: We evaluated adults with LPR symptoms undergoing high-resolution manometry (HRM) and combined hypopharyngeal-esophageal multichannel intraluminal impedance-pH testing at a tertiary center between March 2018 and August 2019. Routine parameters per Chicago classification were obtained on HRM. Proximal esophageal contractility was evaluated using proximal contractile integral (PCI), which quantifies contractile pressure >20 mm Hg for the region spanning the distal margin of the upper esophageal sphincter and transition zone. Univariate (Kendall correlation and Student t test) and multivariable (general linear regression and logistic regression) analyses were performed.

RESULTS: We enrolled 138 patients (66.7% women, mean age 57.1 years) in this study. Lower PCI was associated with an elevated risk of increased pharyngeal reflux (adjusted odds ratio 0.83 per 100 mm Hg-s-cm change in PCI, 95% confidence interval: 0.69-0.98), with a trend toward increased bolus exposure time and total reflux events, after multivariable adjustment. The relationship between PCI and pharyngeal reflux was strongest among participants without a primary motility disorder on HRM (adjusted odds ratio 0.63, 95% confidence interval: 0.42-0.85, P interaction = 0.04). Among continuously expressed reflux parameters, lower PCI was significantly associated with more distal acid reflux events (β = -0.0094, P = 0.03) and total reflux events (β = -0.0172, P = 0.05), after adjusting for confounders.

DISCUSSION: Reduced proximal esophageal contractility as assessed by decreased PCI on HRM independently predicted increased pharyngeal reflux in patients with LPR symptoms, particularly among those without a coexisting motility disorder.

Wong D, Chan WW. Foregut Dysmotility in the Lung Transplant Patient. Current gastroenterology reports. 2021;23(12):23. doi:10.1007/s11894-021-00824-3

PURPOSE OF REVIEW: To explore the role of upper gastrointestinal disease in the clinical course of lung transplant patients - including its pathophysiology, diagnostic testing, and treatment options.

RECENT FINDINGS: Gastroesophageal reflux disease (GERD) and foregut motility disorders are more prevalent among end-stage lung disease patients and are associated with poorer outcomes in lung transplant recipients. A proposed mechanism is the exposure of the lung allograft to aspirated contents, resulting in inflammation and rejection. Diagnostic tools to assess for these disorders include multichannel intraluminal impedance and pH (MII-pH) testing, high resolution esophageal manometry (HREM), and gastric emptying scintigraphy. The main treatment options are medical management with acid suppressants and/or prokinetic agents and anti-reflux surgery. In particular, data support the use of early anti-reflux surgery to improve outcomes. Newer diagnostic tools such as MII-pH testing and HREM allow for the identification of both acid and non-acid reflux and esophageal motility disorders, respectively. Recent studies have demonstrated that early anti-reflux surgery within six months post-transplant better protects against allograft injury and pulmonary function decline when compared to late surgery. However, further prospective research is needed to evaluate the short and long-term outcomes of these diagnostic approaches and interventions.

Okwara NC, Chan WW. Sorting out the Relationship Between Esophageal and Pulmonary Disease. Gastroenterology clinics of North America. 2021;50(4):919-934. doi:10.1016/j.gtc.2021.08.006

The aim of this review is to explore the relationship between esophageal syndromes and pulmonary diseases considering the most recent data available. Prior studies have shown a close relationship between lung diseases such as asthma, chronic obstructive pulmonary disorders (COPD), Idiopathic pulmonary fibrosis (IPF), and lung transplant rejection and esophageal dysfunction. Although the association has long been demonstrated, the exact relationship remains unclear. Clinical experience has shown a bidirectional relationship where esophageal disease may influence the outcomes of pulmonary disease and vice versa. The impact of esophageal dysfunction on pulmonary disorders may also be related to 2 different mechanisms: the reflux pathway leading to microaspiration and the reflex pathway triggering vagally mediated airway reactions. The aim of this review is to further explore these relationships and pathophysiologic mechanisms. Specifically, we discuss the proposed hypotheses for the relationship between the 2 diseases, as well as the pathophysiology and new developments in clinical management.

McCarty TR, Hathorn KE, Redd WD, et al. How Do Presenting Symptoms and Outcomes Differ by Race/Ethnicity Among Hospitalized Patients With Coronavirus Disease 2019 Infection? Experience in Massachusetts. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2021;73(11):e4131-e4138. doi:10.1093/cid/ciaa1245

BACKGROUND: Population-based literature suggests severe acute respiratory syndrome coronavirus 2 infection may disproportionately affect racial/ethnic minorities; however, patient-level observations of hospitalization outcomes by race/ethnicity are limited. Our aim in this study was to characterize coronavirus disease 2019 (COVID-19)-associated morbidity and in-hospital mortality by race/ethnicity.

METHODS: This was a retrospective analysis of 9 Massachusetts hospitals including all consecutive adult patients hospitalized with laboratory-confirmed COVID-19. Measured outcomes were assessed and compared by patient-reported race/ethnicity, classified as white, black, Latinx, Asian, or other. Student t test, Fischer exact test, and multivariable regression analyses were performed.

RESULTS: A total of 379 patients (aged 62.9 ± 16.5 years; 55.7% men) with confirmed COVID-19 were included (49.9% white, 13.7% black, 29.8% Latinx, 3.7% Asian), of which 376 (99.2%) were insured (34.3% private, 41.2% public, 23.8% public with supplement). Latinx patients were younger, had fewer cardiopulmonary disorders, were more likely to be obese, more frequently reported fever and myalgia, and had lower D-dimer levels compared with white patients (P < .05). On multivariable analysis controlling for age, gender, obesity, cardiopulmonary comorbidities, hypertension, and diabetes, no significant differences in in-hospital mortality, intensive care unit admission, or mechanical ventilation by race/ethnicity were found. Diabetes was a significant predictor for mechanical ventilation (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.11-3.23), while older age was a predictor of in-hospital mortality (OR, 4.18; 95% CI, 1.94-9.04).

CONCLUSIONS: In this multicenter cohort of hospitalized COVID-19 patients in the largest health system in Massachusetts, there was no association between race/ethnicity and clinically relevant hospitalization outcomes, including in-hospital mortality, after controlling for key demographic/clinical characteristics. These findings serve to refute suggestions that certain races/ethnicities may be biologically predisposed to poorer COVID-19 outcomes.