BACKGROUND: Laryngopharyngeal symptoms (LPS) refer to upper aerodigestive tract symptoms with etiologic potential for reflux pathophysiology. We aimed to characterize the clinical presentation/evaluation of LPS and identify predictors of laryngopharyngeal reflux disease (LPRD) in an international cohort of patients with LPS.

METHODS: We included adult patients with LPS presenting for esophageal testing at 5 international tertiary centers in 3 world regions. Demographics, clinical symptoms, validated patient-reported outcome instruments and esophageal testing data were obtained. The diagnostic yield of objective gastroesophageal reflux disease (GERD) evidence was compared across LPS presentations. Univariate and multivariable analyses were performed, reported as odds ratios (OR) and 95% confidence intervals (CI).

RESULTS: Of 408 patients (age 53.3±0.7 years, 70% female), 135 (33.1%) had isolated LPS and 273 (66.9%) had LPS with typical reflux symptoms. Symptom burden was higher in LPS with typical symptoms (p≤0.004), as was objective GERD evidence (29.7% vs 17.0%, p=0.006), with similar diagnostic yields between wireless and pH-impedance monitoring in both isolated LPS and LPS with typical symptoms (p=0.36). On multivariable logistic regression evaluating predictors for conclusive GERD, typical symptoms (OR 2.71, CI 1.33-5.55, p=0.006), hiatus hernia (OR 1.80, CI 1.24-2.62, p=0.002) and body mass index (OR 1.08, CI 1.03-1.14, p=0.002) and were independent predictors for conclusive GERD, but LPS type and severity did not predict LPRD. Across world regions, symptom burden was higher despite lower GERD evidence in Asian patients.

CONCLUSIONS: Clinical presentation of isolated LPS is not predictive of LPRD, unlike LPS with typical symptoms. Our findings support the San Diego Consensus recommendations for selective up-front testing in isolated LPS.

Laryngopharyngeal symptoms (LPS) present a diagnostic challenge due to the lack of clear diagnostic gold standard, and suboptimal correlation between traditional esophageal reflux criteria and pharyngeal reflux events. Mean nocturnal baseline impedance (MNBI) is a measure of mucosal integrity that correlates with reflux burden, but evidence for its role in diagnosing laryngopharyngeal reflux disease remains limited. We aimed to characterize the correlation between MNBI and pharyngeal reflux on objective reflux monitoring. This was a retrospective study of adults with LPS undergoing reflux monitoring with hypopharyngeal-esophageal multichannel intraluminal impedance and pH. MNBI was calculated by taking the mean baseline impedance of three 10-minute time periods at rest (1 AM, 2 AM, 3 AM) from the distal electrode pairs (9-11 cm/11-13 cm below the upper esophageal sphincter). Increased pharyngeal reflux was defined as ≥2 events in 24 hours per established criteria. Univariate, multivariable, and receiver-operating characteristic (ROC) curve analyses were performed. One hundred nineteen patients were included (mean age = 55.5 ± 1.4 years, 71.4% female). MNBI inversely correlated with pharyngeal reflux events (r = -0.25, P = 0.009) and was lower in patients with increased pharyngeal reflux (1867 ± 124 Ω vs. 2540 ± 177 Ω, P = 0.0027). On multivariable analysis, MNBI remained independently predictive of increased pharyngeal reflux (OR: 0.94 per 100 Ω increase, 95% CI:0.90-0.98, P = 0.008). On ROC analysis, the area under ROC curve for increased pharyngeal reflux was 0.65, with MNBI thresholds of 1017 Ω and 3474 Ω achieving >90% specificity and sensitivity, respectively. Lower MNBI independently predicts increased pharyngeal reflux in patients with LPS, with potential adjunctive value for laryngopharyngeal reflux disease diagnosis on objective testing.

BACKGROUND: Supragastric belching (SGB) can trigger reflux episodes, but the contribution of SGB to pathological reflux burden is incompletely understood.

OBJECTIVE: To characterise and identify clinical predictors for excessive SGB-related gastro-oesophageal reflux disease (GERD) phenotype.

DESIGN: This was a multicentre cross-sectional study of patients with acid exposure time (AET) >6% on pH-impedance monitoring off therapy across 11 international tertiary centres. SGB episodes were manually identified. Excessive SGB was defined by ≥13 episodes/24 hours. SGB-related AET was determined by duration of pH <4 following an SGB episode. Univariate and multivariable analyses assessed relationships between excessive SGB and conclusive GERD.

RESULTS: Of 580 patients (age 56.1±0.6 year, 62% women) from four world regions (Europe/North America/Latin America/Asia), 107 (18.5%) had excessive SGB (p=0.97 across regions). Excessive SGB-related GERD phenotype had lower total AET (p=0.01) with 24.6±2.2% total AET attributable to SGB, higher total reflux episodes (TRE, p=0.0006) and higher number of SGB-related symptom episodes (p<0.0001). On logistic regression, higher TRE (OR 1.01, 95% CI 1.004 to 1.014, p=0.0004) independently predicted excessive SGB, while predominant perceptive symptoms (heartburn/chest pain, OR 0.36, 95% CI 0.155 to 0.854, p=0.002) and higher distal AET (OR 0.96, 95% CI 0.920 to 0.998, p=0.042) were negative predictors. On receiver-operating characteristics curve analysis, >115 TRE and >56 proximal reflux episodes achieved >90% specificity for excessive SGB.

CONCLUSIONS: Excessive SGB is found in up to 20% of patients with conclusive GERD, with 25% of AET attributable to SGB. Higher TRE (>115 TRE, >56 proximal episodes) and more SGB-associated symptoms are predictors of excessive SGB-related GERD phenotype.

OBJECTIVE: To review the updated literature about epidemiology, clinical presentation, diagnosis, and treatment of laryngopharyngeal reflux disease (LPRD) and to provide a practical management for clinical practice.

DATA SOURCES: PubMED, Cochrane Library, and Scopus.

REVIEW METHOD: Four authors conducted the literature review on LPRD epidemiology, clinical presentation, diagnosis, and treatment according to the PRISMA statement. A critical analysis of the literature and a related management algorithm for clinical practice were provided.

CONCLUSIONS: Studies from the last 5 years provided increased evidence about the gaseous and alkaline profile of LPRD at 24-hour hypopharyngeal-esophageal impedance-pH monitoring, and the presence of alkaline-activated enzymes in the upper aerodigestive tract mucosa. Three consensuses emerged, emphasizing the importance of objective testing to demonstrate LPRD in patients with laryngopharyngeal symptoms. The recent literature suggested that LPRD may be associated with atypical presentations, including posterior nasal inflammation, dry eyes, and middle ear disorders. The predominantly alkaline nature of LPRD has prompted clinical studies supporting alginate and magaldrate over proton pump inhibitors (PPIs), which only target gastric acidity, for managing acid, weakly acid, and alkaline pharyngeal reflux events. Despite a growing literature, there was no randomized controlled trial comparing alginate, magaldrate, diet, and PPIs conducted in the last 5 years.

IMPLICATIONS FOR PRACTICE: The increased evidence about alkalinity of pharyngeal reflux events and the detection of alkaline-activated enzymes in saliva may shift the current PPI-based therapy to alginate therapy. Multicenter international randomized controlled studies with standardized protocols could improve the scientific knowledge about LPRD.

GOALS: To identify clinical features associated with geographic residency in patients with eosinophilic esophagitis (EoE).

BACKGROUND: Prior studies on the geographic distribution of eosinophilic esophagitis (EoE) have focused on disease prevalence. Geographic and environmental factors may impact the clinical characteristics and phenotypes of EoE, although data remain limited.

STUDY: This was a cross-sectional study of consecutive patients residing in Massachusetts with newly diagnosed EoE (≥15 eosinophils/hpf). Patients' residency settings were classified as urban or nonurban based on the 2020 US Census and residential zip codes. Clinical, endoscopic, and histologic variables were recorded. EoE patients in urban versus nonurban settings were compared using the student t test or the Fisher exact test for univariate analyses. Multivariable logistic regression was performed to identify the independent association between urban residency and comorbid atopic conditions, the inflammatory endotype, and the fibrostenotic endotype.

RESULTS: Six hundred eighty-three EoE patients were included, with 136 (20.0%) urban and 547 (80%) nonurban residents. Urban patients had higher rates of atopy (63.2% vs. 51.8%, P =0.02), severe food/environmental allergies (17.7% vs. 8.3%, P =0.002), and inflammatory findings endoscopic (43.4% vs. 27.8%, P =0.0006). On multivariable analysis, atopy (OR=1.57, CI: 1.02-2.40, P =0.04), severe food/environmental allergies (OR=1.99, CI: 1.09-3.63, P =0.02), and inflammatory findings (OR=1.90, CI: 1.22-2.94, P =0.004) remained independently associated with urban residency.

CONCLUSIONS: Urban residency is independently associated with severe food/environmental allergies and inflammatory endoscopic findings at EoE diagnosis, suggesting increased allergic phenotype and active inflammation at presentation. Allergen exposure, particularly indoors, and social determinants may be contributory factors. Environmental considerations, such as geographic residency, may impact EoE disease presentation, activity, and outcome.

BACKGROUND: Since gastroesophageal reflux disease (GERD) manifests typical and atypical symptoms of varying frequency and severity, the dominant symptom needs identification and quantification.

GOALS: We aimed to compare 5-point Likert scales assessing symptom burden to validated GERD questionnaires and outcomes following GERD management.

STUDY: We retrospectively analyzed pooled data from patients undergoing pH-impedance testing for reflux symptoms from 2 centers. Preprocedure questionnaires assessed symptom severity and frequency on 5-point Likert scales (0=not severe, infrequent; 4=extremely severe, multiple daily episodes); the product for the highest scoring symptom constituted the dominant symptom intensity (DSI). DSI was compared against validated instruments [global symptom severity (GSS), GERD questionnaire (GERDQ) and reflux symptom index (RSI)], and pH-impedance parameters per Lyon Consensus 2.0. DSI change after GERD management was compared against GSS and satisfaction with therapy.

RESULTS: Among 808 patients (mean age: 53.8±1.44 y, 65.2% female). DSI significantly correlated with GSS ( R =0.682), GERDQ ( R =0.414), RSI ( R =0.577), acid exposure time (AET) ( R =0.175), total reflux episodes ( R =0.194) and mean nocturnal baseline impedance ( R =-0.157) ( P <0.0001 for each comparison). On ROC analyses, DSI (AUROC=0.60) was noninferior to GSS, GERDQ, and RSI in predicting pathologic AET and total reflux episodes, and conclusive GERD. Percentage DSI improvement after antireflux treatment significantly correlated with GSS change ( R =0.632, P <0.0001) and treatment satisfaction ( R =0.513, P <0.0001) and was an independent predictor of GSS change (β=0.302, P <0.0001), and satisfaction with therapy (β=0.833, P =0.011) on multivariable regression.

CONCLUSIONS: DSI correlates with validated reflux questionnaires and discriminates abnormal from normal reflux burden. DSI change reflects reflux treatment outcome and satisfaction.

BACKGROUND: The San Diego Consensus for Laryngopharyngeal Symptoms (LPS) and Laryngopharyngeal Reflux Disease (LRPD) describes a broad-based multidisciplinary management paradigm that focuses on mechanisms underlying symptoms to improve treatment outcomes.

PURPOSE: This review expands on the San Diego Consensus framework to discuss multidisciplinary management of LPS and LPRD. LPS manifest as persistent or disproportionate symptoms despite minimal or inconsistent evidence of reflux exposure. Emerging evidence suggests that hyperresponsiveness, hypervigilance, and symptom-specific anxiety are more strongly associated with LPS than objective reflux metrics and may contribute to symptom persistence through heightened attention to perceived irritation and protective behavioral responses. Repeated peripheral sensory input may further contribute to central sensitization and lower perceptive thresholds. While these behavioral and neurophysiological processes may be partially improved by reducing reflux exposure, behavioral therapies that address the multidimensional nature of LPS may provide additional benefit. Laryngeal Recalibration Therapy addresses LPS by retraining maladaptive laryngeal behaviors, enhancing vagal tone via heart rate variability biofeedback, and cognitive reframing to reduce symptom amplification. Meta-therapy, a clinical dialogue approach used in speech-language pathology to facilitate behavioral change, alongside psychological interventions such as mindfulness meditation, cognitive-behavioral therapy, and gut-directed hypnotherapy, may further target cognitive-affective processes that shape perception. Behavioral interventions can be combined with neuromodulators, particularly delta ligands such as gabapentin in patients with chronic cough, and tricyclic antidepressants or selective serotonin reuptake inhibitors in select cases. Effective management relies on multidisciplinary collaboration, integration of reflux-directed and behavioral therapies, and patient-centered education that supports adaptive symptom interpretation.

BACKGROUND: Esophageal symptoms are common among elderly patients, although evidence on age-related esophageal dysfunction remains inconsistent. Esophageal contraction reserve measured by response to multiple rapid swallows (MRS) on high-resolution manometry (HRM) provides additional insights beyond conventional HRM metrics. We aimed to evaluate the impact of age on esophageal contraction reserve among symptomatic adults.

METHODS: Adults with esophageal symptoms undergoing HRM and pH-impedance monitoring off acid suppression were included. Patients with prior foregut surgery or major peristaltic disorder were excluded. MRS response was assessed by the ratio of post-MRS distal contractile integral (DCI) to mean DCI from single water swallows, with a ratio > 1 defining a positive response (MRS+).

RESULTS: Among 619 patients (mean 56.5 years, 59.1% female), 372 patients (60.1%) exhibited intact contraction reserve. MRS+ patients were younger (54.3 ± 15.7 vs. 59.8 ± 12.5 years, p < 0.0001) and MRS+ prevalence declined with advancing age groups (< 35 years: 78.8%; 35-50 years: 65.4%; 50-65 years: 59.6%; > 65 years: 51.7%, p-trend = 0.0008). On multivariable logistic regression, age negatively predicted MRS+ (OR: 0.97, CI: 0.96-0.99, p = 0.0004), after adjusting for potential confounders. In separate models constructed with categorized age groups, age > 65 years independently correlated with less MRS+ compared to all younger groups: Age < 35 (OR: 0.23, CI: 0.10-0.53, p = 0.0005), age 35-50 (OR: 0.58, 95% CI: 0.31-0.98, p = 0.045), and age 50-65 (OR: 0.55, 95% CI: 0.33-0.90, p = 0.017).

CONCLUSION: Esophageal contraction reserve measured by MRS during HRM declines with advancing age. Age-related loss of contractile adaptability may contribute to esophageal dysfunction and unexplained symptoms in older adults. Provocative testing with MRS on HRM provides value in evaluating symptomatic elderly patients.