Publications by Year: 2021


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.

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.

Sikavi DR, Cai JX, Carroll TL, Chan WW. Prevalence and clinical significance of esophageal motility disorders in patients with laryngopharyngeal reflux symptoms. Journal of gastroenterology and hepatology. 2021;36(8):2076-2082. doi:10.1111/jgh.15391

BACKGROUND AND AIM: Esophageal motor dysfunction may underlie impaired bolus/refluxate clearance in laryngopharyngeal reflux (LPR). However, the prevalence of esophageal dysmotility and its correlation with reflux parameters and symptoms in LPR is not well established. The aim of this study was to evaluate the prevalence of coexisting esophageal dysmotility among patients with suspected LPR.

METHODS: This was a retrospective cohort study of 194 consecutive patients with LPR symptoms referred for high-resolution manometry (HRM) and combined hypopharyngeal-esophageal multichannel intraluminal impedance and pH testing at a tertiary center in March 2018 to August 2019. Validated symptom surveys were prospectively collected at time of testing, including Reflux Symptom Index, Gastroesophageal Reflux Disease Questionnaire, dominant symptom intensity, and 12-Item Short-Form Health Survey. HRM findings were categorized using Chicago Classification v3.0.

RESULTS: Abnormal findings on HRM were identified in 84 (43.3%) patients, with ineffective esophageal motility (n = 60, 30.9%) as the most common diagnosis. A disorder of esophagogastric junction outflow or a major disorder of peristalsis was identified in 26 (13.4%) patients, including 2 (1%) with achalasia and 7 (3.6%) with jackhammer esophagus. Reflux burden (distal, proximal, or pharyngeal) on combined hypopharyngeal-esophageal multichannel intraluminal impedance and pH testing did not differ across HRM findings. Patients reporting esophageal symptoms were more likely to have a primary motility disorder (odds ratio 2.34, P = 0.04). However, no significant differences in Reflux Symptom Index, Gastroesophageal Reflux Disease Questionnaire, or 12-Item Short-Form Health Survey were noted across HRM diagnoses.

CONCLUSION: Esophageal motility disorders are prevalent among patients with LPR symptoms, including up to one in seven with esophagogastric junction outflow or major peristaltic disorder. Patients with abnormal motility more likely report esophageal symptoms. Clinicians should be aware of these coexisting conditions, particularly in those with refractory symptoms.

Kim D, Adeniji N, Latt N, et al. Predictors of Outcomes of COVID-19 in Patients With Chronic Liver Disease: US Multi-center Study. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2021;19(7):1469-1479.e19. doi:10.1016/j.cgh.2020.09.027

BACKGROUND & AIMS: Chronic liver disease (CLD) represents a major global health burden. We undertook this study to identify the factors associated with adverse outcomes in patients with CLD who acquire the novel coronavirus-2019 (COVID-19).

METHODS: We conducted a multi-center, observational cohort study across 21 institutions in the United States (US) of adult patients with CLD and laboratory-confirmed diagnosis of COVID-19 between March 1, 2020 and May 30, 2020. We performed survival analysis to identify independent predictors of all-cause mortality and COVID-19 related mortality, and multivariate logistic regression to determine the risk of severe COVID-19 in patients with CLD.

RESULTS: Of the 978 patients in our cohort, 867 patients (mean age 56.9 ± 14.5 years, 55% male) met inclusion criteria. The overall all-cause mortality was 14.0% (n = 121), and 61.7% (n = 535) had severe COVID-19. Patients presenting with diarrhea or nausea/vomiting were more likely to have severe COVID-19. The liver-specific factors associated with independent risk of higher overall mortality were alcohol-related liver disease (ALD) (hazard ratio [HR] 2.42, 95% confidence interval [CI] 1.29-4.55), decompensated cirrhosis (HR 2.91 [1.70-5.00]) and hepatocellular carcinoma (HCC) (HR 3.31 [1.53-7.16]). Other factors were increasing age, diabetes, hypertension, chronic obstructive pulmonary disease and current smoker. Hispanic ethnicity (odds ratio [OR] 2.33 [1.47-3.70]) and decompensated cirrhosis (OR 2.50 [1.20-5.21]) were independently associated with risk for severe COVID-19.

CONCLUSIONS: The risk factors which predict higher overall mortality among patients with CLD and COVID-19 are ALD, decompensated cirrhosis and HCC. Hispanic ethnicity and decompensated cirrhosis are associated with severe COVID-19. Our results will enable risk stratification and personalization of the management of patients with CLD and COVID-19. number NCT04439084.

McCarty TR, Hathorn KE, Chan WW, Jajoo K. Endoscopic band ligation in the treatment of gastric antral vascular ectasia: a systematic review and meta-analysis. Endoscopy international open. 2021;9(7):E1145-E1157. doi:10.1055/a-1401-9880

Background and study aims  While argon plasma coagulation (APC) is the first-line treatment for gastric antral vascular ectasia (GAVE), endoscopic band ligation (EBL) has shown promising results. The aim of this study was to perform a systematic review and meta-analysis to evaluate the effectiveness of EBL for the treatment of GAVE. Methods  Individualized search strategies were developed in accordance with PRISMA and MOOSE guidelines through September 1, 2020. Measured outcomes included endoscopic success (defined as GAVE eradication/improvement), change in hemoglobin, transfusion dependency, number of treatment sessions, adverse events, rebleeding, and bleeding-associated mortality. Outcomes were compared among studies evaluating EBL versus APC. Results  Eleven studies (n = 393; 59.39 % female; mean age 58.65 ± 8.85 years) were included. Endoscopic success was achieved in 87.84 % [(95 % CI, 80.25 to 92.78); I 2  = 11.96 %] with a mean number of 2.50 ± 0.49 treatment sessions and average of 12.40 ± 3.82 bands applied. For 8 studies comparing EBL (n = 143) versus APC (n = 174), there was no difference in baseline patient characteristics. However, endoscopic success was significantly higher for EBL [OR 6.04 (95 % CI 1.97 to 18.56; P  = 0.002], requiring fewer treatment sessions (2.56 ± 0.81 versus 3.78 ± 1.17; P  < 0.001). EBL was also associated with a greater increase in post-procedure hemoglobin [mean difference 0.35 (95 % CI 0.07 to 0.62; P  = 0.0140], greater reduction in transfusions required [mean difference -1.46 (95 % CI -2.80 to -0.12; P  = 0.033], and fewer rebleeding events [OR 0.11 (95 % CI, 0.04 to 0.36); P  < 0.001]. There was no difference in adverse events or bleeding-associated mortality ( P  > 0.050). Conclusions  EBL appears to be safe and effective for treatment of GAVE, with improved outcomes when compared to APC.