Prevalence of functional esophageal disorders and associated clinical characteristics in patients with proton-pump-inhibitor-unresponsive reflux symptoms.

BACKGROUND AND AIM: Patients with proton-pump-inhibitor (PPI)-unresponsive reflux symptoms, often caused by functional esophageal disorders (FED), are frequently encountered in clinical practice. We aimed to investigate the prevalence of FED and its associated clinical characteristics in patients with PPI-unresponsive reflux symptoms. METHODS: We retrospectively identified patients who were evaluated for persistent typical reflux symptoms, despite ≥8 weeks of PPI treatment, at the National Taiwan University Hospital from 2014 to 2023. All patients underwent a comprehensive evaluation comprising validated gastroesophageal reflux disease (GERD) symptom questionnaires, 5-item Brief Symptom Rating Scale (BSRS-5), Pittsburgh Sleep Quality Index (PSQI), esophagogastroduodenoscopy, high-resolution impedance manometry, and 24-h impedance-pH monitoring off PPI therapy. Diagnosis of FED and non-erosive reflux disease (NERD) was based on the Rome IV criteria. RESULTS: We analyzed 190 patients [46.8% male, median age 52 (interquartile range, 42-61) years], of whom 32 (16.8%) had NERD and 158 (83.2%) had FED (57.9% with functional heartburn and 25.3% with reflux hypersensitivity). Patients with FED had a lower body mass index than those with NERD and a higher prevalence of psychological comorbidities and poor sleep quality than healthy volunteers. The severity of reflux symptoms among FED patients was significantly associated with the severity of psychological comorbidities and sleep quality. CONCLUSIONS: A notably high prevalence (83.2%) of FED was observed among patients experiencing PPI-unresponsive reflux symptoms. Patients with FED had a higher level of psychological distress and diminished sleep quality, both of which were associated with reflux symptom severity.

Proton Pump Inhibitor-unresponsive Laryngeal Symptoms Are Associated With Psychological Comorbidities and Sleep Disturbance: A Manometry and Impedance-pH Monitoring Study

Background/Aims: Laryngeal symptoms are largely treated with empiric proton pump inhibitor (PPI) therapy if no apparent pathology shown on ear, nose, and throat evaluation and reflux-related etiologies are suspected. However, treatment response remains unsatisfactory. This study aimed to investigate the clinical and physiological characteristics of patients with PPI-refractory laryngeal symptoms. Methods: Patients with persistent laryngeal symptoms despite PPI treatment for ≥ 8 weeks were recruited. A multidisciplinary evaluation comprising validated questionnaires for laryngeal symptoms (reflux symptom index [RSI]), gastroesophageal reflux disease symptoms, psychological comorbidity (5-item brief symptom rating scale [BSRS-5]) and sleep disturbance (Pittsburgh sleep quality index [PSQI]), esophagogastroduodenoscopy, ambulatory impedance-pH monitoring, and high-resolution impedance manometry were performed. Healthy asymptomatic individuals were also recruited for comparison of psychological morbidity and sleep disturbances. Results: Ninety-seven adult patients and 48 healthy volunteers were analyzed. The patients had markedly higher prevalence of psychological distress (52.6% vs 2.1%, P < 0.001) and sleep disturbance (82.5% vs 37.5%, P < 0.001) than the healthy volunteers. There were significant correlations between RSI and BSRS-5 scores, and between RSI and PSQI scores (r = 0.26, P = 0.010, and r = 0.29, P = 0.004, respectively). Fifty-eight patients had concurrent gastroesophageal reflux disease symptoms. They had more prominent sleep disturbances (89.7% vs 71.8%, P < 0.001) than those with laryngeal symptoms alone but similar reflux profiles and esophageal motility. Conclusions: PPI-refractory laryngeal symptoms are mostly associated with psychological comorbidities and sleep disturbances. Recognition of these psychosocial comorbidities may help optimize management in these patients.

Clinical Characteristics and Associated Psychosocial Dysfunction in Patients With Functional Dysphagia: A Study Based on High-Resolution Impedance Manometry and Rome IV Criteria.

INTRODUCTION: The pathophysiology of functional dysphagia as defined by the updated Rome IV criteria is complex and remains largely unknown. We aimed to investigate its clinical characteristics and its association with psychosocial comorbidities. METHODS: Consecutive patients referred to our motility laboratory for evaluation of esophageal dysphagia were identified. All patients were assessed with upper endoscopy, high-resolution impedance manometry, and validated symptom questionnaires. Data from those who were diagnosed with functional dysphagia (n = 96) based on the Rome IV criteria were analyzed. Age- and sex-adjusted healthy volunteers were also enrolled for comparison. Psychiatric comorbidity and poor sleep quality were defined as total score of 5-item Brief Symptom Rating Scale ≥6 and Pittsburgh Sleep Quality Index ≥6, respectively. RESULTS: The age peak of patients with functional dysphagia was at 40-60 years (47.9%) with females predominant (67%). Forty-four patients (45.8%) had psychiatric comorbidities, whereas 80 (83.3%) experienced poor sleep quality. Female patients were more likely to have trouble falling asleep, shorter sleep duration, and severe bloating. Compared with the healthy volunteers, patients with functional dysphagia had higher 5-item Brief Symptom Rating Scale and Pittsburgh Sleep Quality Index scores (5.34 ± 3.91 vs 1.84 ± 2.61, 9.64 ± 4.13 vs 4.77 ± 3.60, both P < 0.001) but similar results on high-resolution impedance manometry. Those with ineffective esophageal motility (16.7%) had less sleep efficiency than those with normal motility. DISCUSSION: Patients with functional dysphagia were mainly middle-aged women and had a high prevalence of psychiatric comorbidities and sleep disturbances, especially in female patients. Patients with functional dysphagia displayed similar esophageal motility as the healthy volunteers did.

Anatomical and physiological characteristics in patients with Laryngopharyngeal Reflux Symptoms: A case-control study utilizing high-resolution impedance manometry.

BACKGROUND/PURPOSE: This study aimed to explore the anatomical and physiological characteristics of patients with laryngopharyngeal reflux (LPR) symptoms, such as hoarseness, throat clearing, throat pain, globus, and chronic cough, with the novel high-resolution impedance manometry (HRIM). METHODS: Consecutive patients exhibited at least one LPR symptom for ≥4 weeks after 2-month proton-pump inhibitor treatment were enrolled during November 2014 and March 2018 from single tertiary medical center. All patients completed validated symptom questionnaires, esophagogastroduodenoscopy, and HRIM. Healthy volunteers were also recruited for comparison of esophageal parameters on HRIM. RESULTS: Eighty-nine LPR patients and 63 healthy volunteers were analyzed. Compared with healthy volunteers, LPR patients had significantly shorter upper and lower esophageal sphincters (UES and LES), a shorter intraabdominal esophagus (all P < 0.01), higher 4-s integrated relaxation pressures (IRP-4s) (P = 0.011) of the LES. After adjusted for age, sex, body weight, body height and alcohol consumption, multiple regression analysis showed that age, LES IRP-4s and the UES length were independent risk factors for LPR symptoms (OR 1.056, 95% CI 1.019-1.094; OR 1.107, 95% CI 1.004-1.222; OR 0.432, 95% CI 0.254-0.736, respectively). In subgroup analysis, patients with moderate LPR symptoms had lower IRP-4s (6.64 ± 4.55 vs. 8.69 ± 5.10, P = 0.049) and more failed peristalsis (27.33 ± 29.26 vs. 11.36 ± 21.20, P = 0.004) than those with mild LPR symptoms. CONCLUSION: Our study suggests that esophageal structural factors and LES IRP-4s may contribute to the occurrence of LPR symptoms. Patients with moderate LPR symptoms were more likely to present with failed peristalsis.

Combination of Symptom Profile, Endoscopic Findings, and Esophageal Mucosal Histopathology Helps to Differentiate Achalasia from Refractory Gastroesophageal Reflux Disease.

Achalasia, a rare primary esophageal motility disorder, is often misdiagnosed as refractory gastroesophageal reflux disease (GERD). This study is aimed to identify the clinical and histopathologic features that may help to differentiate these two entities. Patients with untreated achalasia and those with refractory reflux symptoms despite ≥8 weeks of proton-pump inhibitor treatment were enrolled prospectively. All patients underwent validated symptom questionnaires, esophagogastroduodenoscopy with biopsy, and high-resolution impedance manometry (HRIM). Histopathology of esophageal mucosa was compared based on four pre-determined histological criteria: basal cell hyperplasia or papillae elongation, eosinophilic infiltration, petechiae formation, and hypertrophy of the muscularis mucosae (MM). Compared with the GERD patients, patients with achalasia had similar reflux symptoms, but higher Eckardt scores, fewer erosive esophagitis and hiatal hernia, more esophageal food retention on endoscopy, and higher prevalence of hypertrophy of the MM and petechiae formation on histopathology. Multivariate logistic regression based on Eckardt score ≥4, normal esophagogastric junction morphology or esophageal food retention, and coexistence of petechiae formation and hypertrophy of the MM, established the best prediction model for achalasia. Therefore, combination of routinely accessible variables, including Eckardt score, endoscopic features, and histopathology obtained via esophageal mucosal biopsy, may provide an earlier identification of achalasia.

Etiologies and clinical characteristics of non-obstructive dysphagia in a Taiwanese population: A prospective study based on high-resolution impedance manometry.

BACKGROUND: Esophageal motility disorders are the major cause of non-obstructive dysphagia (NOD), but may be underdiagnosed. In this high-resolution impedance manometry (HRIM)-based study, we aimed to clarify the etiologies and clinical characteristics of patients presenting with NOD in a Taiwanese population. METHODS: From October 2014 to July 2017, consecutive patients with the chief complaint of dysphagia were prospectively enrolled in the study at a tertiary medical center. All subjects underwent a comprehensive diagnostic work-up, which included validated symptom questionnaires, esophagogastroduodenoscopy, timed barium esophagogram, and HRIM. Those with obstructive esophageal lesions were excluded. Esophageal motility disorders were diagnosed using the updated Chicago Classification v3.0. We categorized all patients based on the HRIM results, and compared the clinical characteristics and parameters between groups. RESULTS: A total of 120 patients (55 men; mean age [range], 52 [13-87] years) were analyzed. Achalasia was the most common diagnosis by HRIM (n = 66, 55%), followed by ineffective esophageal motility (n = 15, 12.5%), and absent contractility (n = 6, 5%). Patients with achalasia experienced increased vomiting (62.1% vs. 31.5%, p = 0.001), significant weight loss (22.7% vs. 7.4%, p = 0.025), delayed esophageal emptying (90.9% vs. 12.9%, p < 0.001), and abnormal bolus transit (100% vs. 25.9%, p < 0.001) compared with non-achalasia patients. CONCLUSION: Based on HRIM and the updated Chicago Classification, achalasia was the most common diagnosis of NOD in a Taiwanese population. HRIM allows for a more detailed assessment and may assist in the tailoring of further treatment plans.