PUBLICATIONS
2023
Esophageal disorders are prevalent among patients with chronic lung diseases, including idiopathic pulmonary fibrosis (IPF). Gastroesophageal reflux disease (GERD) has been associated with IPF prevalence, severity, and respiratory decline. The pathophysiologic relationship between GERD and IPF is likely bidirectional, with aspiration of refluxate leading to lung inflammation and fibrosis, while the restrictive pulmonary physiology may contribute to altered transdiaphragmatic pressure gradient and increased reflux. Esophageal symptoms are frequently absent and do not predict esophageal dysfunction or pathologic reflux in patients with IPF, and objective diagnostic tools including upper endoscopy, ambulatory reflux monitoring, and high-resolution manometry are often needed. Impedance-based testing that identifies both weakly/non-acidic and acid reflux may provide important additional diagnostic value beyond pH-based acid testing alone. Novel metrics and maneuvers, including advanced impedance measures on impedance-pH study and provocative testing on HRM, may hold promise to future diagnostic advancements. The main treatment options include medical therapy with acid suppressants and anti-reflux surgery, although their potential benefits in pulmonary outcomes of IPF require further validations. Future directions of research include identifying phenotypes of IPF patients who may benefit from esophageal testing and treatment, determining the optimal testing strategy and protocol, and prospectively assessing the value of different esophageal therapies to improve outcomes while minimizing risks. This review will discuss the pathophysiology, evaluation, and management of esophageal diseases, particularly GERD, in patients with IPF, as informed by the most recent publications in the field, in hopes of identifying targets for future study and research.
BACKGROUND: Laryngopharyngeal reflux (LPR) is a common otolaryngologic diagnosis. Treatment of presumed LPR remains challenging, and limited frameworks exist to guide treatment.
METHODS: Using RAND/University of California, Los Angeles (UCLA) Appropriateness Methods, a modified Delphi approach identified consensus statements to guide LPR treatment. Experts independently and blindly scored proposed statements on importance, scientific acceptability, usability, and feasibility in a four-round iterative process. Accepted measures reached scores with ≥ 80% agreement in the 7-9 range (on a 9-point Likert scale) across all four categories.
RESULTS: Fifteen experts rated 36 proposed initial statements. In round one, 10 (27.8%) statements were rated as valid. In round two, 8 statements were modified based on panel suggestions, and experts subsequently rated 5 of these statements as valid. Round three's discussion refined statements not yet accepted, and in round four, additional voting identified 2 additional statements as valid. In total, 17 (47.2%) best practice statements reached consensus, touching on topics as varied as role of empiric treatment, medication use, lifestyle modifications, and indications for laryngoscopy.
CONCLUSION: Using a well-tested methodology, best practice statements in the treatment of LPR were identified. The statements serve to guide physicians on LPR treatment considerations.
INTRODUCTION: Gastroesophageal reflux has been associated with poorer lung transplantation outcomes, although no standard approach to evaluation/management has been adopted. We aimed to evaluate the effect of timely antireflux treatment as guided by routine reflux testing on postlung transplant rejection outcomes.
METHODS: This was a retrospective cohort study of lung transplant recipients at a tertiary center. All patients underwent pretransplant ambulatory pH monitoring. Timely antireflux treatment was defined as proton pump inhibitor initiation or antireflux surgery within 6 months of transplantation. Patients were separated into 3 groups: normal pH monitoring (-pH), increased reflux (+pH) with timely treatment, and +pH with delayed treatment. Rejection outcomes included acute rejection, bronchiolitis obliterans syndrome, and chronic lung allograft dysfunction per International Society for Heart and Lung Transplantation criteria. Time-to-event analyses using Cox proportional hazard models were applied. Patients not meeting outcomes were censored at death or last clinic visit.
RESULTS: One hundred seventy-five patients (59% men/mean 56.3 yr/follow-up: 496 person-years) were included. On multivariable analyses, +pH/delayed treatment patients had higher risks of acute rejection (adjust hazard ratio [aHR]:3.81 [95% confidence interval [CI]: 1.90-7.64], P = 0.0002), bronchiolitis obliterans syndrome (aHR: 2.22 [95% CI: 1.07-4.58], P = 0.03), and chronic lung allograft dysfunction (aHR: 2.97 [95% CI: 1.40-6.32], P = 0.005) than +pH/timely treatment patients. Similarly, rejection risks were increased among +pH/delayed treatment patients vs -pH patients (all P < 0.05). No significant differences in rejection risks were noted between +pH/timely treatment patients and -pH patients. Failure/complications of antireflux treatment were rare and similar among groups.
DISCUSSION: Timely antireflux treatment, as directed by pretransplant reflux testing, was associated with reduced allograft rejection risks and demonstrated noninferiority to patients without reflux. A standardized peri-transplant test-and-treat algorithm may guide timely reflux management to improve lung transplant outcomes.
2022
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.
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.