Faculty Bibliography

PURPOSE OF REVIEW/OBJECTIVE:To describe the relationship between reflux and bronchiectasis and to appraise recent literature on reflux characterization, clinical outcomes, and management strategies in patients with bronchiectasis. RECENT FINDINGS/RESULTS:Reflux is common in bronchiectasis and has been linked to worse respiratory symptoms and quality of life, more exacerbations and healthcare use, lower lung function, and higher mortality. These associations are seen across several cohorts, but nearly all data are observational, use variable reflux definitions, and cannot determine whether reflux contributes to bronchiectasis progression or simply identifies patients with more severe disease. Proposed pathways include microaspiration-related airway injury, reflex-mediated cough amplification, and microbial dysbiosis. No randomized bronchiectasis-specific trial has shown improved respiratory outcomes with reflux-directed therapy, and acid suppression alone is unlikely to address nonacid reflux, microaspiration, cough-reflex pathways, or airway dysbiosis. SUMMARY/CONCLUSIONS:In bronchiectasis, reflux should be separated into clinically relevant phenotypes, including typical gastroesophageal reflux disease, proximal or nonacid reflux, laryngopharyngeal symptoms, dysphagia, and aspiration. Management should be guided by the suspected reflux or aspiration pattern because acid suppression alone may not address airway-relevant reflux. Future studies should pair objective reflux and swallowing measures with bronchiectasis-specific outcomes.

A 96-hour ambulatory pH testing is a practical tool for diagnosing gastroesophageal reflux disease (GERD) and for concurrently evaluating two conditions: dietary variation and its effect on measured acid exposure time (AET) and reported symptoms. To date, it is unknown how consuming a diet of either low or high acidity can influence pathologic GERD. This study aimed to assess the effects of high- and low-acid diets on AET and the occurrence of laryngopharyngeal symptoms (LPS) during prolonged wireless pH monitoring. A retrospective review of 208 patients who underwent 96-hour wireless pH monitoring for GERD evaluation was completed. Patients consumed a primarily high-acid diet on 1 day and a primarily low-acid diet on a separate day during the 96-hour period. Patients were considered to have pathologic GERD if esophageal AET was >6% for the time with pH <4, and were considered normal on an individual day if the AET was <4%. Pathologic GERD was found in 78 patients (37.5%), of whom the majority (55%) recorded their lowest AET during the study on their low-acid day. Only 24.7% achieved normal AET on a low-acid diet day. Mean AET on a high-acid diet, compared with a low-acid diet, decreased by 41%, from 12.51 to 7.33, with a similarly proportional decrease in patients negative for GERD. There was no significant difference between patients with and without LPS with regard to esophageal acid exposure on high- and low-acid diet days (P = 0.73, P = 0.81). A low-acid diet may be a viable lifestyle modification when used as monotherapy or adjunctively with proton pump inhibitor in patients with or without pathologic GERD.

OBJECTIVE:The videofluoroscopic swallow study (VFSS) is an evaluation of the anatomy and physiology of swallowing, and often includes a screening evaluation of the esophagus. How the esophageal screen translates to esophageal pathology remains unknown. The purpose of this study was to determine if abnormal esophageal clearance (EC) on VFSS correlates with esophageal function on high-resolution esophageal manometry (HREM). MATERIALS AND METHODS/METHODS:This is a retrospective review of 115 adult patients who underwent both VFSS with esophageal screen and HRM. EC on VFSS was scored with the modified barium swallow impairment profile (MBSImP) component 17. Motility was characterized using HRM metrics according to the Chicago Classification Version 4.0 (CCv4.0). Predictive metrics were calculated for the esophageal screen. RESULTS:An EC score o greater than or equal to 1 had a sensitivity of 66%, specificity of 57%, PPV of 52%, NPV of 70%, and OR of 2.55 (p = 0.027). EC weakly correlated with incomplete bolus clearance (rho = 0.331, p = 0.0004) and did not correlate with bolus transit time (rho = 0.17, p = 0.105). CONCLUSIONS:The esophageal screen as characterized by the MBSImP is not an effective predictor of esophageal function on HREM as defined by the CCv4.0. Future work may focus on a defining a standardized VFSS protocol for the esophageal screen and potentially a more nuanced assessment of esophageal findings on VFSS that may enhance the sensitivity of the modality to motility disorders.

INTRODUCTION/BACKGROUND:Despite the high prevalence of typical symptoms of gastroesophageal reflux disease (GERD), approximately 30% of patients have functional esophageal disorders (FED) on ambulatory reflux monitoring, which may include reflux hypersensitivity (RH; defined as physiologic acid exposure but temporally correlated symptoms of reflux), or functional heartburn (FH; defined as physiologic acid exposure and negative symptom correlation). There are limited epidemiological data characterizing these conditions. We investigated demographic and socioeconomic factors as well as medical comorbidities which may predispose to FED versus pathologic GERD. METHODS:Adult patients with reflux symptoms for at least 3 months were studied with 24-h pH-impedance testing from 11/2019 to 3/2021. Participants were categorized into pathologic GERD, FH, or RH using pH-impedance data and reported symptom correlation. Demographic data, including age, gender, race/ethnicity, zip code, insurance status, and medical comorbidity data were retrospectively retrieved from the electronic medical record on all participants. RESULTS:229 patients were included. Non-Hispanic Asian ethnicity (OR 5.65; p = 0.01), underweight BMI (OR 7.33; p = 0.06), chronic pain (OR 2.33; p < 0.01), insomnia (OR 2.83; p = 0.06), and allergic rhinitis (OR 3.90; p < 0.01) were associated with a greater risk for FED. Overweight BMI (OR 0.48; p = 0.03) and alcohol use (OR 0.57; p = 0.06) were associated with a decreased risk for FED. DISCUSSION/CONCLUSIONS:This is the first report of a greater risk of FED in patients with underweight BMI, insomnia, chronic pain, allergic rhinitis, or of Asian or Hispanic ethnicities. The weak associations between female gender and anxiety are corroborated in other studies. Our findings enable clinicians to better screen patients with reflux for this disorder.

It is well established that there is an increased risk of esophageal malignancy associated with achalasia, with esophageal squamous cell carcinoma being the most common histologic subtype thought to be secondary to the detrimental effects of food and saliva stasis resulting from poor esophageal emptying. Esophageal adenocarcinoma has also been found in this population with majority of these cases occurring after achalasia treatment, presumably as a result of iatrogenic reflux. Nevertheless, the benefits of cancer screening in this population remains an area of controversy. We reviewed the literature examining the pathogenesis of malignancy among patients with achalasia and the current data examining the potential strategies for long-term surveillance in this patient population.

The first coronavirus disease 2019 (COVID-19) pandemic surge harshly impacted the medically underserved populations of the urbanized northeastern United States. SARS-CoV-2 virions infect the gastrointestinal (GI) tract, and GI symptoms are common during acute infection.1 Post-COVID syndromes increasingly are recognized as important public health considerations.2 Postinfectious disorders of gut-brain interaction (DGBIs; formerly known as functional gastrointestinal disorders) can occur after enteric illness; the COVID-19 pandemic is anticipated to provoke DGBI development3 within a rapidly evolving post-COVID framework of illness. Here, we evaluate factors associated with DGBI-like post-COVID gastrointestinal disorders (PCGIDs) in our hospital's surrounding communities comprised predominantly of racial/ethnic minorities and those of reduced socioeconomic status.

BACKGROUND & AIMS:We aimed to compare safety and effectiveness of vedolizumab to tumor necrosis factor (TNF)-antagonist therapy in ulcerative colitis in routine practice. METHODS:A multicenter, retrospective, observational cohort study (May 2014 to December 2017) of ulcerative colitis patients treated with vedolizumab or TNF-antagonist therapy. Propensity score weighted comparisons for development of serious adverse events and achievement of clinical remission, steroid-free clinical remission, and steroid-free deep remission. A priori determined subgroup comparisons in TNF-antagonist-naïve and -exposed patients, and for vedolizumab against infliximab and subcutaneous TNF-antagonists separately. RESULTS:A total of 722 (454 vedolizumab, 268 TNF antagonist) patients were included. Vedolizumab-treated patients were more likely to achieve clinical remission (hazard ratio [HR], 1.651; 95% confidence interval [CI], 1.229-2.217), steroid-free clinical remission (HR, 1.828; 95% CI, 1.135-2.944), and steroid-free deep remission (HR, 2.819; 95% CI, 1.496-5.310) than those treated with TNF antagonists. Results were consistent across subgroup analyses in TNF-antagonist-naïve and -exposed patients, and for vedolizumab vs infliximab and vs subcutaneous TNF-antagonist agents separately. Overall, there were no statistically significant differences in the risk of serious adverse events (HR, 0.899; 95% CI, 0.502-1.612) or serious infections (HR, 1.235; 95% CI, 0.608-2.511) between vedolizumab-treated and TNF-antagonist-treated patients. However, in TNF-antagonist-naïve patients, vedolizumab was less likely to be associated with serious adverse events than TNF antagonists (HR, 0.192; 95% CI, 0.049-0.754). CONCLUSIONS:Treatment of ulcerative colitis with vedolizumab is associated with higher rates of remission than treatment with TNF-antagonist therapy in routine practice, and lower rates of serious adverse events in TNF-antagonist-naïve patients.

BACKGROUND & AIMS:We created and validated a clinical decision support tool (CDST) to predict outcomes of vedolizumab therapy for ulcerative colitis (UC). METHODS:We performed logistic regression analyses of data from the GEMINI 1 trial, from 620 patients with UC who received vedolizumab induction and maintenance therapy (derivation cohort), to identify factors associated with corticosteroid-free remission (full Mayo score of 2 or less, no subscore above 1). We used these factors to develop a model to predict outcomes of treatment, which we called the vedolizumab CDST. We evaluated the correlation between exposure and efficacy. We validated the CDST in using data from 199 patients treated with vedolizumab in routine practice in the United States from May 2014 through December 2017. RESULTS:Absence of exposure to a tumor necrosis factor (TNF) antagonist (+3 points), disease duration of 2 y or more (+3 points), baseline endoscopic activity (moderate vs severe) (+2 points), and baseline albumin concentration (+0.65 points per 1 g/L) were independently associated with corticosteroid-free remission during vedolizumab therapy. Patients in the derivation and validation cohorts were assigned to groups of low (CDST score, 26 points or less), intermediate (CDST score, 27-32 points), or high (CDST score, 33 points or more) probability of vedolizumab response. We observed a statistically significant linear relationship between probability group and efficacy (area under the receiver operating characteristic curve, 0.65), as well as drug exposure (P < .001) in the derivation cohort. In the validation cohort, a cutoff value of 26 points identified patients who did not respond to vedolizumab with high sensitivity (93%); only the low and intermediate probability groups benefited from reducing intervals of vedolizumab administration due to lack of response (P = .02). The vedolizumab CDST did not identify patients with corticosteroid-free remission during TNF antagonist therapy. CONCLUSIONS:We used data from a trial of patients with UC to develop a scoring system, called the CDST, which identified patients most likely to enter corticosteroid-free remission during vedolizumab therapy, but not anti-TNF therapy. We validated the vedolizumab CDST in a separate cohort of patients in clinical practice. The CDST identified patients most likely to benefited from reducing intervals of vedolizumab administration due to lack of initial response. ClinicalTrials.gov no: NCT00783718.

BACKGROUND & AIMS:There are few real-world data on the safety of vedolizumab for treatment of Crohn's disease (CD) or ulcerative colitis (UC). We quantified rates and identified factors significantly associated with infectious and non-infectious adverse events in clinical practice. METHODS:We performed a retrospective review of data from a multicenter consortium database (from May 2014 through June 2017). Infectious and non-infectious adverse events were defined as those requiring antibiotics, hospitalization, vedolizumab discontinuation, or resulting in death. Rates were quantified as proportions and events per 100 patient years of exposure (PYE) or follow up (PYF). We performed multivariable logistic regression analyses to identify factors significantly associated with events and reported as odds ratios (OR) with 95% CIs. RESULTS:Our analysis comprised 1087 patients (650 with CD and 437 with UC; 55% female; median age, 37 years) with 861 PYE and 955 PYF. Infections were observed in 68 patients (6.3%; 7.9 per 100 PYE, 7.1 per 100 PYF); gastrointestinal infections (n = 31, 2.4 per 100 PYE, 2.2 per 100 PYF) and respiratory infections (n = 14, 1.6 per 100 PYE, 1.5 per 100 PYF) were the most common. Arthralgias were the most common non-infectious adverse events (n = 31, 2.9%; 3.6 per 100 PYE). Two patients developed malignancies (squamous cell skin cancer and colorectal cancer; 0.23 per 100 PYE, 0.21 per 100 PYF). Active smoker status (OR, 3.39) and number of concomitant immunosuppressive agents (corticosteroids or immunomodulators; OR, 1.72 per agent) used were independently associated with infections. CONCLUSION:In a retrospective cohort study of patients with IBD, we found vedolizumab to be well tolerated with an overall favorable safety profile. Active smoking and concomitant use of immunosuppressive agents were independently associated with infections.