Salgado S, Borges LF, Cai JX, Lo WK, Carroll TL, Chan WW. Symptoms classically attributed to laryngopharyngeal reflux correlate poorly with pharyngeal reflux events on multichannel intraluminal impedance testing. Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus. 2022;36(1). doi:10.1093/dote/doac041

Laryngopharyngeal reflux (LPR) is thought to be a common etiology of throat and airway symptoms. Diagnosis of LPR is challenging, given the variable symptomatology and response to therapy. Identifying symptoms that better correlate with LPR may inform management strategies. We aimed to examine the association between patient-reported symptoms and objectively identified LPR on ambulatory reflux monitoring. This was a retrospective cohort study of consecutive adults with suspected LPR undergoing combined hypopharyngeal-esophageal multichannel intraluminal impedance-pH testing (HEMII-pH) at a tertiary center. All patients completed standardized symptom surveys for presenting symptoms, reflux symptom index (RSI), and voice handicap index (VHI). LPR was defined as >1 full-column pharyngeal reflux event on HEMII-pH over 24 hours. Univariate and multivariable analyses were performed. A total of 133 patients were included (mean age = 55.9 years, 69.9% female). Of this 83 (62.4%) reported concomitant esophageal symptoms. RSI and VHI did not correlate with proximal esophageal or pharyngeal reflux events (Kendall's tau correlations P > 0.05), although the mean RSI was higher in the LPR group (21.1 ± 18.9 vs. 17.1 ± 8.3, P = 0.044). Cough, but not other laryngeal symptoms, was more common among patients with esophageal symptoms (58% vs. 36%, P = 0.014). Neither laryngeal symptoms nor esophageal symptoms of reflux predicted LPR on univariate or multivariable analyses (all P > 0.05). Neither laryngeal symptoms classically attributed to LPR nor typical esophageal symptoms correlated with pharyngeal reflux events on HEMII-pH. Clinical symptoms alone are not sufficient to make an LPR diagnosis. Broad evaluation for competing differential diagnoses and objective reflux monitoring should be considered in patients with suspected LPR symptoms.

Borges LF, Salgado S, Hathorn KE, Feldman N, Carroll TL, Chan WW. Failed Swallows on High-Resolution Manometry Independently Correlates With Severity of LPR Symptoms. Journal of voice : official journal of the Voice Foundation. 2022;36(6):832-837. doi:10.1016/j.jvoice.2020.09.003

BACKGROUND: Abnormal esophageal motility is prevalent in gastroesophageal reflux disease patients; however, its relationship with laryngopharyngeal reflux (LPR) symptom severity remains unclear. Altered esophageal transit may contribute to LPR symptoms. We aimed to examine the relationship between reflux symptom index (RSI), a validated questionnaire for LPR symptoms, and abnormal esophageal motility on high-resolution manometry (HRM).

METHODS: A total of 133 consecutive patients (55.9 ± 14.6 years, 69.9% female) with suspected LPR referred for HRM and multichannel intraluminal impedance-pH study (MII-pH) at a tertiary center from March 2015 to October 2017 were included. RSI questionnaire was prospectively collected prior to motility testing. Authors analyzing HRM and MII-pH were blinded to RSI findings. Statistical analyses were performed using Student's t test or Pearson's correlation (univariate) and general linear regression (multivariable).

RESULTS: Mean RSI was higher among patients with ineffective esophageal motility than those with normal motility (23.7 vs 18.6, P = 0.01). Significant positive correlation was found between RSI and percent failed swallows (R2 = 0.21, P = 0.03), but not percent weak swallows. On multivariable analysis, percent ineffective (failed or weak) swallows was significantly associated with RSI (β-coefficient: 0.072, P = 0.05) after controlling for age, gender, BMI, smoking, prior PPI use, and reflux on MII-pH. When analyzed separately, percent failed swallows (β-coefficient: 0.095, P= 0.02), but not percent weak swallows, independently predicted higher RSI.

CONCLUSIONS: Ineffective swallows, particularly failed swallows, are independently associated with higher RSI in patients with suspected LPR, even after controlling for reflux on MII-pH. Esophageal dysmotility may play a role in suspected LPR symptoms independent of reflux. HRM should be routinely considered in evaluating these patients.

Hamilton MJ, Muftah M, Goldin AH, et al. Overlapping Transcriptional Profile in Proton Pump Inhibitor Responsive and Nonresponsive Eosinophilic Esophagitis. Clinical and translational gastroenterology. 2022;13(11):e00540. doi:10.14309/ctg.0000000000000540

INTRODUCTION: We compared esophageal mucosal gene transcript expression in proton pump inhibitor (PPI) responsive (PPI-R) eosinophilic esophagitis (EoE), PPI nonresponsive (PPI-NR) EoE, and healthy controls.

METHODS: Transcript expression in midesophagus biopsies was determined using NanoString and a custom panel of EoE-specific genes. The top upregulated and downregulated genes with ≥2-fold difference in expression and statistically significant ( P < 0.05) were identified.

RESULTS: Nearly all the top upregulated (17 of 20) and downregulated (5 of 5) genes in EoE, compared with healthy controls, were shared between the PPI-R and PPI-NR groups.

DISCUSSION: Esophageal mucosal transcript expressions are remarkably similar in PPI-R EoE and PPI-NR EoE compared with healthy controls.

Nan K, Babaee S, Chan WW, et al. Low-cost gastrointestinal manometry via silicone-liquid-metal pressure transducers resembling a quipu. Nature biomedical engineering. 2022;6(10):1092-1104. doi:10.1038/s41551-022-00859-5

The evaluation of the tone and contractile patterns of the gastrointestinal (GI) tract via manometry is essential for the diagnosis of GI motility disorders. However, manometry is expensive and relies on complex and bulky instrumentation. Here we report the development and performance of an inexpensive and easy-to-manufacture catheter-like device for capturing manometric data across the dynamic range observed in the human GI tract. The device, which we designed to resemble the quipu-knotted strings used by Andean civilizations for the capture and transmission of information-consists of knotted piezoresistive pressure sensors made by infusing a liquid metal (eutectic gallium-indium) through thin silicone tubing. By exploring a range of knotting configurations, we identified optimal design schemes that led to sensing performances comparable to those of commercial devices for GI manometry, as we show for the sensing of GI motility in multiple anatomic sites of the GI tract of anaesthetized pigs. Disposable and customizable piezoresistive catheters may broaden the use of GI manometry in low-resource settings.

Lechien JR, Chan WW, Akst LM, et al. Normative Ambulatory Reflux Monitoring Metrics for Laryngopharyngeal Reflux: A Systematic Review of 720 Healthy Individuals. Otolaryngology–head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2022;166(5):802-819. doi:10.1177/01945998211029831

OBJECTIVES: To review the normative data for acid, weakly acid, and nonacid proximal esophageal (PRE) and hypopharyngeal reflux (HRE) events in diagnosing laryngopharyngeal reflux (LPR) using ambulatory reflux monitoring.

DATA SOURCES: PubMed, Cochrane Library, and Scopus.

REVIEW METHODS: A literature search was conducted about the normative data for PRE and HRE on multichannel intraluminal impedance-pH monitoring (MII-pH), hypopharyngeal-esophageal MII-pH (HEMII-pH), or oropharyngeal pH monitoring using PICOTS (population, intervention, comparison, outcome, timing, and setting) and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statements. Outcomes reviewed included device characteristics, impedance/pH sensor placements, study duration, number/average and percentiles of PRE or HRE occurrence, and the event characteristics (pH, composition, and position).

RESULTS: Of 154 identified studies, 18 met criteria for analysis, including 720 healthy individuals. HEMII-pH, MII-pH, and oropharyngeal pH monitoring were used in 7, 6, and 5 studies, respectively. The definition and inclusion/exclusion criteria of healthy individuals varied substantially across studies, with 6 studies considering only digestive symptoms to exclude potential LPR patients. Substantial heterogeneity across studies was noted, including impedance/pH sensor placements/configurations and definitions of composition (liquid, gas, mixed) and type (acid, weakly acid, nonacid) of PRE/HRE. The 95th percentile thresholds were 10 to 73 events for PRE, 0 to 10 events for HRE on HEMII-pH, and 40 to 128 for events with pH <6.0 on oropharyngeal pH monitoring. Most HREs were nonacid and occurred upright. The mean HRE among healthy individuals was 1.

CONCLUSION: The low number of studies and the heterogeneity in inclusion criteria, definitions, and characterization of PRE and HRE limit the establishment of consensual normative criteria for LPR on ambulatory reflux monitoring. Future large multicenter studies are needed.

McCarty TR, Jirapinyo P, James LP, Gupta S, Chan WW, Thompson CC. Transoral incisionless fundoplication is cost-effective for treatment of gastroesophageal reflux disease. Endoscopy international open. 2022;10(7):E923-E932. doi:10.1055/a-1783-9378

Background and study aims  Given the sizable number of patients with symptomatic gastroesophageal reflux disease (GERD) despite proton pump inhibitor (PPI) therapy, non-pharmacologic treatment has become increasingly utilized. The aim of this study was to analyze the cost-effectiveness of medical, endoscopic, and surgical treatment of GERD. Patients and methods  A deterministic Markov cohort model was constructed from the US healthcare payer's perspective to evaluate the cost-effectiveness of three competing strategies: 1) omeprazole 20 mg twice daily; 2) transoral incisionless fundoplication (TIF 2.0); and 3) laparoscopic Nissen fundoplication [LNF]. Cost was reported in US dollars with health outcomes recorded in quality-adjusted life years (QALYs). Ten-year and lifetime time horizons were utilized with 3 % discount rate and half-cycle corrections applied. The main outcome was incremental cost-effectiveness ratio (ICER) with a willingness-to-pay threshold of $ 100,000 per QALY. Probabilistic sensitivity analyses were also performed. Results  In our base-case analysis, the average cost of TIF 2.0 was $ 13,978.63 versus $ 17,658.47 for LNF and $ 10,931.49 for PPI. Compared to the PPI strategy, TIF 2.0 was cost-effective with an incremental cost of $ 3,047 and incremental effectiveness of 0.29 QALYs, resulting in an ICER of $ 10,423.17 /QALY gained. LNF was strongly dominated by TIF 2.0. Over a lifetime horizon, TIF 2.0 remained the cost-effective strategy for patients with symptoms despite twice-daily 20-mg omeprazole. TIF 2.0 remained cost-effective after varying parameter inputs in deterministic and probabilistic sensitivity analyses and for scenario analyses in multiple age groups. Conclusions  Based upon this study, TIF 2.0 was cost-effective for patients with symptomatic GERD despite low-dose, twice-daily PPI.

Lodhia NA, Horton L, Thapa N, Goldin AH, Chan WW. Opioid-Associated Anorectal Dysfunction in Chronic Constipation. Digestive diseases and sciences. 2022;67(8):3904-3910. doi:10.1007/s10620-021-07288-5

INTRODUCTION: The role of anorectal and defecatory dysfunction in opioid-related constipation is unclear. We aimed to evaluate the relationship between opioid use and rectal sensation, defecatory function, and balloon expulsion on anorectal physiology testing.

METHODS: This was a retrospective cohort study of consecutive adults undergoing high-resolution anorectal manometry (HRAM) at a tertiary center for constipation. Clinical characteristics, medication use, and HRAM findings were obtained. Statistical analyses were performed using Fisher-exact/student t-test for univariate analyses and logistic/general linear regression for multivariable analyses to compare patients with no opioid use, recent (< 3 months) use, and distant (> 3 months) use.

RESULTS: 424 patients (49.8 ± 17.2 years; 85.6% female) were included. Compared to those without opioid history, patients with recent use had increased volumes for first rectal sensation (70.4 mL vs 59.4, p = 0.043), urge (120.5 mL vs 101.5, p = 0.017), and maximal tolerance (170.2 mL vs 147.2, p = 0.0018), but not patients with distant use. Recent opioid use was associated with increased risk of dyssynergic defecation (DD) (61.8% vs 46.4%, p = 0.035), but not failed balloon expulsion. On multivariable models controlling for potential confounders, recent opioid use, but not distant use, remained independently correlated with increased volumes for first rectal sensation (β-coefficient 9.78, p = 0.019), urge (β-coefficient 16.7, p = 0.0060), and maximal tolerance (β-coefficient 22.9, p = 0.0032), and higher risk for DD (aOR = 2.18, p = 0.026).

CONCLUSION: Recent opioid use was an independent risk factor for rectal hyposensitivity and DD on HRAM in patients with constipation, but that effect may decrease with discontinuation of use. Anorectal physiology testing should be considered in patients with opioid-associated constipation.