Esophageal Hypervigilance and Visceral Anxiety Contribute to Symptom Severity of Laryngopharyngeal Reflux.

INTRODUCTION: Laryngopharyngeal reflux (LPR) is a clinical conundrum without a diagnostic gold standard. The Esophageal Hypervigilance and Anxiety Scale (EHAS) is a questionnaire designed for cognitive-affective evaluation of visceral sensitivity. We hypothesized that esophageal hypervigilance and symptom-specific anxiety have an etiopathological role in generation of LPR symptoms, especially when gastroesophageal reflux disease (GERD) cannot explain these symptoms. METHODS: Consecutive patients with LPR and/or GERD symptoms lasting >3 months were prospectively enrolled and characterized using the Reflux Symptom Index, GERD questionnaire, and EHAS. Eligible patients with negative endoscopy underwent 24-hour impedance-pH monitoring off acid suppression for phenotyping GERD and assessment of reflux burden, using conventional metrics (acid exposure time and number of reflux episodes) and novel metrics (mean nocturnal baseline impedance and postreflux swallow-induced peristaltic wave index). RESULTS: Of 269 enrolled patients (mean age 47.1 years, 21-65 years, 60.6% female), 90 patients were with concomitant GERD and LPR symptoms, 32 patients were with dominant LPR symptoms, 102 patients were with dominant GERD symptoms, and 45 were controls. Patients with concomitant GERD and LPR symptoms had higher EHAS than those with dominant GERD symptoms and controls ( P ≤ 0.001); patients with dominant LPR symptoms had higher EHAS than controls ( P = 0.007). On Pearson correlation, EHAS positively correlated with the Reflux Symptom Index. DISCUSSION: Esophageal hypervigilance and symptom-specific anxiety may be more important than reflux burden in LPR symptom perception.

Esophageal acid burden in reflux patients with normal endoscopy: Does esophageal peristalsis matter?

BACKGROUND: A majority of patients with gastroesophageal reflux disease (GERD) have normal endoscopy. We aimed to investigate whether esophageal primary and secondary peristalsis influence esophageal reflux parameters in patients with normal endoscopy. METHODS: We enrolled consecutive patients with typical reflux symptoms and normal endoscopy. All patients underwent High resolution manometry (HRM) and 24-h impedance-pH studies off therapy. During HRM, secondary peristalsis was evaluated using ten 20-mL rapid air infusions into the esophagus, while primary peristalsis was evaluated using ten 5-mL water swallows. RESULTS: A total of 43 patients completed the study; 13 patients had normal motility, 20 had ineffective esophageal motility (IEM), and 10 had absent contractility. Acid exposure time (AET) (total, supine, and upright) was significantly higher in those with absent primary peristalsis (absent contractility) compared to normal motility (P = 0.001; 0.01; 0.007) and IEM (P = 0.002; 0.02; 0.03). Supine AET was significantly higher in patients without secondary peristalsis compared to those with secondary peristalsis (P = 0.04). CONCLUSION: In the setting of normal endoscopy, acid reflux burden is more profound in patients with absent primary peristalsis, as well as in patients lacking a secondary peristaltic response to esophageal air distension.

Effects of phosphodiesterase-5 inhibitor sildenafil on esophageal secondary peristalsis: Studies with high-resolution manometry.

BACKGROUND AND AIM: Secondary peristalsis contributes to the clearance of retained refluxate from the esophagus. Sildenafil, a phosphodiesterase-5 inhibitor, inhibits primary esophageal peristalsis, but its effects on secondary peristalsis remain unknown. This study sought to investigate whether sildenafil could influence physiological characteristics of secondary peristalsis by applying high-resolution manometry (HRM). METHODS: Seventeen healthy volunteers (15 men and 2 women, aged 30.2 ± 6.4 years) underwent two HRM studies on separate days following the administration of either a placebo or 50 mg of sildenafil in a random order. Both studies were performed using a water-perfused HRM catheter containing one air injection channel positioned in the mid-esophagus. Secondary peristalsis was stimulated by a rapid mid-esophageal injection of 10 or 20 mL of air 1 h after the administration of either the placebo or sildenafil. The frequency and distal contractile integral of secondary peristalsis were then compared. RESULTS: Complete secondary peristalsis triggered by the 20-mL air injection was more frequent than observed with the 10-mL air injection (P < 0.001). The vigor of secondary peristalsis triggered by the injection of either volume of air was lower than that of primary peristalsis (P < 0.001). Sildenafil significantly reduced the success rate (P ≤ 0.001) and vigor (P < 0.001) of secondary peristalsis relative to the effects of the placebo at both distension volumes. CONCLUSIONS: Secondary peristalsis can be successfully triggered by rapid air injection during HRM. Sildenafil reduces both the success rate and the vigor of secondary peristalsis, similar to that seen with primary peristalsis.

Effects of codeine on esophageal peristalsis in humans using high resolution manometry.

BACKGROUND AND AIM: Opioid receptors agonists have been demonstrated to impair lower esophageal sphincter (LES) relaxation and induce spastic esophageal dysmotility, but little was known for their impact on distension-induced secondary peristalsis. The aim of the study was to investigate the hypothesis whether acute administration of codeine can influence physiological characteristics of primary and secondary peristalsis in healthy adults. METHODS: Eighteen healthy volunteers (13 men, mean age 27.5 years, aged 20-43 years) underwent high resolution manometry (HRM) with a catheter containing an injection port in mid-esophagus. Secondary peristalsis was performed with 10 and 20 mL rapid air injections. Two different sessions including acute administration of codeine (60 mg) or the placebo were randomly performed. RESULTS: Codeine significantly increased 4-s integrated relaxation pressure (IRP-4s) (P = 0.003) and shortened distal latency (DL) (P = 0.003) of primary peristalsis. The IRP-4s of secondary peristalsis was also significantly higher after codeine than the placebo during air injections with 10 mL (P = 0.048) and 20 mL (P = 0.047). Codeine significantly increased the frequency of secondary peristalsis during air injections with 10 mL than the placebo (P = 0.007), but not for air injection with 20 mL (P = 0.305). CONCLUSIONS: In addition to impair LES relaxation and reduce distal latency of primary peristalsis, codeine impairs LES relaxation of secondary peristalsis and increases secondary peristaltic frequency. Our study supports the notion in human esophagus that the impact of opioids on peristaltic physiology appears to be present in both primary and secondary peristalsis.

Effect of prucalopride on sildenafil-induced inhibition of esophageal peristalsis in healthy adults.

BACKGROUND AND AIM: Prucalopride, a high-affinity 5-hydroxytryptamine 4 receptor agonist, promotes esophageal peristalsis, while phosphodiesterase type 5 inhibitor sildenafil inhibits esophageal peristalsis. The present study was aimed to evaluate whether prucalopride would augment esophageal peristalsis subsequent to the application of sildenafil. METHODS: Seventeen healthy adults underwent high-resolution manometry by a catheter with one injection port located in the mid-esophagus. Secondary peristalsis was assessed by rapid air injections after water swallows. Two sessions were randomly performed including acute administration of sildenafil 50 mg after pretreatment with prucalopride or the placebo. RESULTS: The frequency of primary peristalsis subsequent to the administration of sildenafil was significantly increased by prucalopride (P = 0.02). Prucalopride also significantly increased distal contractile integral of primary peristalsis subsequent to the administration of sildenafil (P = 0.03). No difference in the frequency of secondary peristalsis subsequent to the administration of sildenafil for air injects of 10 mL (P = 0.14) or 20 mL (P = 0.21) was found between prucalopride and placebo. Prucalopride did not change distal contractile integral of secondary peristalsis subsequent to the administration of sildenafil for air injections of 10 mL (P = 0.09) or 20 mL (P = 0.12). CONCLUSIONS: Prucalopride modulates sildenafil-induced inhibition of primary peristalsis by increasing its effectiveness and peristaltic wave amplitude. Our findings suggest that activation of 5-hydroxytryptamine 4 receptors plays a role in mediating sildenafil-induced inhibition of esophageal primary peristalsis rather than secondary peristalsis.

Similarities and differences between IBS-C and FC with regards to symptomatology, sleep quality and psychological attributes.

BACKGROUND: Irritable bowel syndrome (IBS) and functional constipation (FC) are highly prevalent in the general population and have significant symptom overlap, while the clinical associations and psychological links between IBS and FC remains poorly understood. We aimed to compare the clinical, metabolic and psychological factors between patients with FC patients and constipation predominated IBS. METHODS: We consecutively enrolled 360 patients from the outpatient clinics of Hualien Tzu Chi medical center. Constipation-predominant IBS (IBS-C) and FC were diagnosed based on Rome III criteria. All participants completed the Pittsburg Sleep Quality Index (PSQI) score, the State Trait Anxiety Inventory (STAI) score and the Taiwanese Depression Questionnaire (TDQ) score. RESULTS: Fifty-four patients had FC and twenty-three patients had IBS-C. Compared to asymptomatic controls, FC/IBS-C groups had female predominance (p < 0.001), FC as well as more GI discomforts and inferior psychosocial characteristics (p < 0.05). Compared to FC, IBS-C had higher severity scores of abdominal distention (4.52 ± 1.90 vs. 3.07 ± 1.88) and heartburn (2.17 ± 1.50 vs. 1.46 ± 1.14). However, FC was independently associated with poor sleep quality [adjusted OR: 1.19 (1.08-1.31), p < 0.001] and IBS-C with depression [adjusted OR: 1.07 (1.02-1.12), p = 0.005]. CONCLUSION: Patients with FC and IBS-C shared many similar GI complaints and psychosocial characteristics, however IBS-C had more severe bloating, heartburn and depression and FC had worse sleeping quality.

Evaluation of Baseline Impedance During Water-perfused High Resolution Impedance Manometry in Patients With Symptomatic GERD.

GOALS: We aimed to investigate the hypothesis whether baseline impedance measured during water-perfused high resolution impedance manometry (HRIM) can help discriminate patients with reflux symptoms from the controls and predict the response to the proton pump inhibitors (PPIs). BACKGROUND/AIM: Baseline impedance measured during solid-state HRIM can reliably discriminate patients with gastroesophageal reflux disease (GERD) from controls. STUDY: We enrolled consecutive patients with typical reflux symptoms and healthy controls for the measurement of baseline impedance during the landmark period of HRIM. All patients were given PPIs and PPI response was assessed after 8 weeks of the treatment. RESULTS: Baseline mucosa impedance measured during HRIM was lower in GERD patients than the controls (1861±183 vs. 3371±250 Ω; P<0.001). Baseline impedance during water-perfused HRIM had moderate diagnostic accuracy for differentiating symptomatic GERD with an area under the curve of 0.853 on receiver operating characteristics analysis. A threshold of 2530 Ω for baseline impedance had a sensitivity of 88.3% and specificity of 82.4% for GERD with a positive predictive value of 83.4% and negative predictive value of 87.6%. Among symptomatic GERD patients, poor PPI responders had higher baseline impedance than those without it (2340±260 vs. 1479±189 Ω; P=0.02). BMI negatively correlated to base impedance in either controls (r=-0.59; P=0.012) or GERD patients (r=-0.47; P=0.047). CONCLUSIONS: Baseline impedance measurement during water-perfused HRIM helps differentiate patients with typical reflux symptoms from controls and also serves as a potential utility in predicting PPI response.

Gamma-aminobutyric acid receptor type B agonist baclofen inhibits acid-induced excitation of secondary peristalsis but not heartburn sensation.

BACKGROUND AND AIM: Acute esophageal acid infusion promotes distension-induced secondary peristalsis. The gamma-aminobutyric acid receptor type B (GABA-B) receptors activation inhibits secondary peristalsis. This study aimed to test the hypothesis whether acid excitation of secondary peristalsis can be influenced by baclofen. METHODS: Secondary peristalsis was performed with intra-esophageal slow and rapid air injections in 13 healthy subjects. Direct esophageal infusion of 0.1 N HCl following pretreatment with placebo or baclofen was randomly performed at least 1 week apart. Symptom intensity, distension thresholds, and peristaltic parameters were determined and compared between each study protocol. RESULTS: The intensity of heartburn symptom in response to esophageal acid infusion was significantly greater with baclofen than the placebo (P = 0.002). The threshold volume of secondary peristalsis during slow air injections in response to acid infusion was significantly greater with baclofen than the placebo (P = 0.001). Baclofen significantly increased the threshold volume of secondary peristalsis during rapid air injections in response to acid infusion (P = 0.001). The frequency of secondary peristalsis in response to acid infusion was significantly decreased by baclofen as compared with the placebo (P = 0.001). Baclofen significantly decreased peristaltic amplitudes in response to acid infusion during rapid air injections (P = 0.007). CONCLUSIONS: Gamma-aminobutyric acid receptor type B agonist baclofen inhibits acid excitation of secondary peristalsis in human esophagus, which is probably mediated by both muscular and mucosal mechanoreceptors. This work supports the evidence of potential involvement of GABA-B receptors in negative modulation of acid excitation of esophageal perception as well as secondary peristalsis.

Clinical and psychological characteristics in gastroesophageal reflux disease patients overlapping with laryngopharyngeal reflux symptoms.

BACKGROUND AND AIM: Laryngopharyngeal reflux (LPR) defined as reflux of gastric content reaching above the upper esophageal sphincter is frequently found in patients with gastroesophageal reflux disease (GERD). This study aimed to investigate clinical and psychological differences between GERD patients with or without LPR symptoms. METHODS: This study enrolled 303 consecutive patients with proton pump inhibitor treatment-naïve scheduled for upper endoscopy because of troublesome reflux symptoms and recognized as GERD by non-dyspepsia reflux disease questionnaire score. Included GERD patients were further categorized into two study groups: with or without LPR by reflux symptoms index score. All participants were also evaluated with questionnaires for depression, anxiety, and sleep disturbances. RESULTS: There were 132 (43.6%) GERD patients with LPR symptoms and 171 (56.4%) GERD patients without LPR symptoms. GERD patients with LPR symptoms had more depression (P < 0.001), sleep disturbance (P = 0.002), irritable bowel syndrome (P = 0.008), functional dyspepsia (P = 0.005), and reflux symptoms burden (P < 0.001) than those without LPR symptoms. Erosive esophagitis was more in patients without LPR symptoms (P = 0.03). GERD patients with LPR symptoms (28.8%) had more complex psychological distress than those without LPR symptoms (28.8% vs 14%, P < 0.001). Reflux symptoms burden, sleep disturbance, and erosive esophagitis were independently associated with GERD overlapping with LPR symptoms. CONCLUSIONS: Gastroesophageal reflux disease patients with LPR symptoms appear to have more reflux symptoms, psychological distress, and functional gastrointestinal disturbance but less erosive esophagitis. This work suggests that therapeutic strategy with tailored multidimensional approach is promising for GERD patients overlapping with LPR symptoms.

Sleep Disturbance and Its Association with Gastrointestinal Symptoms/Diseases and Psychological Comorbidity.

BACKGROUND/AIMS: We aimed to investigate gastrointestinal symptoms, clinical characteristics, and psychological factors in subjects with and without sleep disturbance (SD) in a health screening cohort. METHODS: We enrolled 2,752 consecutive subjects during their health checkups. All participants underwent an evaluation with questionnaires. Demographic characteristics and biochemical data were recorded. SD was confirmed when Pittsburgh Sleep Quality Index score was greater than 5. RESULTS: Among the study population (n = 2,674), 956 (36%) individuals had SD. SD was associated with female gender, older age, lower level of education, higher systolic blood pressure, higher serum high-density lipoprotein levels and higher prevalence of functional dyspepsia and irritable bowel syndrome (IBS). SD subjects also had more depression, more anxiety, more severe gastrointestinal reflux disease symptoms and higher prevalence of non-erosive reflux disease (NERD; p < 0.001). SD was -independently associated with female gender (OR 1.75, p < 0.001), older age (OR 1.03, p < 0.001), NERD (OR 1.88, p = 0.004), IBS (OR 1.51, p = 0.043), and depression (OR 1.16, p < 0.001) by multivariate analysis. CONCLUSIONS: Future studies will be needed to clarify the interrelationships among SD, psychological stress, and functional gastrointestinal disorders.

Assessment of esophageal function using provocative tests during high resolution manometry: A single-center experience.

BACKGROUND: Provocative tests were used to provide additional information during performing high resolution manometry (HRM). The study aimed to evaluate whether it is feasible to test esophageal function with different esophageal provocative tests during HRM. METHODS: 23 healthy volunteers (9 women; mean age 25 years, range 21-30 years) underwent water-perfused HRM. Each subject received 10 liquid swallows, 10 solid swallows, 10 liquid swallows with abdominal compression, and 5 multiple rapid swallowing (MRS). RESULTS: DCI was significantly greater during abdominal compression than that of solid swallows (p = 0.025). Compared with liquid swallows, there was a significant decrease in CFV during solid swallows (p = 0.04). DL was significantly greater during solid swallows than that of liquid swallows (p < 0.001) or abdominal compression (p < 0.001). IRP 4s was significantly lower during abdominal compression than that of liquids (p < 0.001) or solid swallows (p = 0.006). All subjects had complete inhibition during MRS and increased DCI after MRS as compared with liquid swallows (p < 0.05). CONCLUSION: Esophageal provocative test may provide additional utility in performing HRM studies. The data for esophageal provocative tests are distinct from standard liquid swallows.

Association of coffee consumption and liver fibrosis progression in patients with HBeAg-negative chronic hepatitis B: A 5-year population-based cohort study.

BACKGROUND/PURPOSE: Although coffee consumption has been associated with decreased risk of liver fibrosis progression, cirrhosis or hepatocellular carcinoma in patients with HCV infection or fatty liver diseases, its effect on hepatitis B patients remains unclear. We aimed to examine the effect of coffee consumption on liver fibrosis progression and cirrhosis-related complications in patients with chronic HBV infection. METHODS: Coffee consumption was assessed in 2604 participants who were previously recruited from a population-based GERD survey. The primary endpoints of this study were the impact of coffee consumption on the development of cirrhosis-related complications, including liver cirrhosis, esophageal varices, or hepatocellular carcinoma at the end of 5-year follow-up. The secondary endpoints were the declines of serum predicting indices of liver fibrosis (AST/ALT, APRI, FIB-4, Hui score) or liver function tests (AST, ALT). RESULTS: 328 patients with chronic HBV infection were enrolled into this study. At baseline, coffee consumption was associated with higher education level, more frequent tobacco use and normal blood pressure (p < 0.05 for all). Patients with higher coffee consumption had a significant lower serum AST, APRI and FIB-4 index value than non-coffee drinkers [adjusted HR 0.30, 95% CI(0.11-0.82) for AST; 0.30, 95% CI (0.11-0.84) for APRI; 0.30, 95% CI (0.13-0.69) for FIB-4]. However, higher coffee consumption didn't change serum AST levels, APRI, FIB-4 index values or incidences of cirrhosis-related complications at the end of 5-year follow-up. CONCLUSION: Coffee consumption was not associated with fibrosis progression or HCC risk in chronic hepatitis B patients over the 5-year observation period.

Impact of concomitant dyspepsia and irritable bowel syndrome on symptom burden in patients with gastroesophageal reflux disease.

BACKGROUND: Patients with gastroesophageal reflux disease (GERD) frequently report symptoms like dyspepsia or/and irritable bowel syndrome (IBS). The aim of the study was to investigate the impact of symptom overlap on GERD symptom burden. We also investigate whether GERD overlapping dyspepsia or/and IBS would have different clinical and psychological features as compared with GERD alone. METHODS: A total of 2752 subjects were screened from a health check-up population. We compared the clinical and psychological factors among subjects with GERD alone and with overlap of two or all three diseases. All participants underwent an evaluation with questionnaires including Reflux Disease Questionnaire score, Pittsburgh Sleep Quality Index, Taiwanese Depression Questionnaire, and State-Trait Anxiety Inventory before receiving endoscopic exam. RESULTS: Among the GERD population, we identified 26 with IBS (GERD-IBS), 60 with dyspepsia (GERD-D), and 25 subjects with overlap of all three conditions (GERD-D-IBS). GERD-D and GERD-D-IBS subjects had more severe GERD symptoms as compared subjects with GERD alone (p < 0.001). Subjects with overlapping dyspepsia or/and IBS showed a significant increase in the severity of depression and poorer sleep quality than subjects with GERD alone. Notably, anxiety scores did not differ significantly between subjects with overlapping diseases and GERD alone. CONCLUSION: Our study demonstrates that disease overlap in GERD population is associated with greater symptom burden, higher depression and poorer sleep quality, but not with anxiety. This study highlights the importance of identifying overlapping conditions as a therapeutic strategy for better management of GERD.

Influence of prucalopride on esophageal secondary peristalsis in reflux patients with ineffective motility.

BACKGROUND AND AIM: Ineffective esophageal motility (IEM) is associated with gastroesophageal reflux disease. Secondary peristalsis contributes to esophageal clearance. Prucalopride promotes secondary peristalsis by stimulating 5-hydroxytrypatamine 4 receptors in the esophagus. We aimed to determine whether prucalopride would augment secondary peristalsis in gastroesophageal reflux disease patients with IEM. METHODS: After a baseline recording of primary peristalsis, secondary peristalsis was stimulated by slow and rapid mid-esophageal injections of air in 15 patients with IEM. Two separate sessions with 4-mg oral prucalopride or placebo were randomly performed. RESULTS: Prucalopride significantly increased primary peristaltic wave amplitude (68.1 ± 10.0 vs 55.5 ± 8.8 mmHg, P = 0.02). The threshold volume for triggering secondary peristalsis was significantly decreased by prucalopride during slow (9.3 ± 0.8 vs 12.0 ± 0.8 mL; P = 0.04) and rapid air injection (4.9 ± 0.3 vs 7.1 ± 0.1 mL; P = 0.01). Secondary peristalsis was triggered more frequently after application of prucalopride (55% [43-70%]) than placebo (45% [33-50%]) (P = 0.008). Prucalopride did not change pressure wave amplitudes during slow air injection (84.6 ± 8.1 vs 57.4 ± 13.8 mmHg; P = 0.19) or pressure wave amplitudes during rapid air injection (84.2 ± 8.6 vs 69.5 ± 12.9 mmHg; P = 0.09). CONCLUSIONS: Prucalopride enhances primary peristalsis and mechanosensitivity of secondary peristalsis with limited impact on secondary peristaltic activities in IEM patients. Our study suggests that prucalopride appears to be useful in augmenting secondary peristalsis in patients with IEM only via sensory modulation of esophageal secondary peristalsis.

Relevance of sleep disturbance to the integrity and characteristics of secondary peristalsis in patients with gastroesophageal reflux disease.

OBJECTIVE: Sleep disturbance is common in patients with gastroesophageal reflux disease (GERD). Secondary peristalsis is important for clearance of the refluxate from the esophagus. We aimed to test the hypothesis whether secondary peristalsis is impaired in GERD patients with sleep disturbance. METHODS: Secondary peristalsis was stimulated with slow and rapid air injections into mid-esophagus in 8 age-matched health controls and 41 patients with GERD. Sleep disturbance was assessed by the Pittsburg Sleep Quality Index (PSQI). Objective sleep measures were assessed by ambulatory actigraphy. RESULTS: The threshold volume for inducing secondary peristalsis during slow air injection was significantly higher in GERD patients with sleep disturbance than healthy controls (14.3 ± 1.2 vs. 8.9 ± 0.5 mL, p < .05). GERD patients with sleep disturbance had higher threshold volume of secondary peristalsis during rapid air injection than GERD patients without sleep disturbance (5.1 ± 0.4 vs. 3.9 ± 0.2 mL, p < .05) and healthy controls (5.1 ± 0.4 vs. 3.6 ± 0.2 mL, p < .05). There was a negative correlation between PSQI score and peristaltic frequency during rapid air injection (r = -.39, p = .01). Secondary peristaltic amplitude during rapid air injection was negatively correlated with wake after sleep onset (r = -.34, p = .04). CONCLUSIONS: Sleep disturbance is associated with secondary peristaltic response to distension-induced esophageal stimulation in patients with GERD. Our study suggests that sleep disturbance per se may adversely influence the effectiveness of esophageal peristalsis and bolus clearance during sleep in patients with GERD.

Endoscopic meatus scoring scale versus sniff test to predict insertability before transnasal endoscopy: A prospective, randomized study.

BACKGROUND AND AIM: Sniff test is a common method before unsedated transnasal esophago-gastro-duodenoscopy (UT-EGD) to select a nostril insertion site. Yet there is no objective method to select a more specific meatus insertion tract for anesthesia and insertion. We devised an endoscopic meatus scoring scale by anterior meatuscopy to select the most optimal meatus insertion tract. We hypothesized that meatuscopy instead of sniff test might improve tolerance and reduce adverse events during nasal anesthesia and UT-EGD. METHODS: A prospective randomized controlled trial to compare patient tolerance and adverse events. RESULTS: A total of 359 patients were assessed and finally 310 patients were analyzed. There were no statistical differences in patient characteristics and insertion failure rates. Pain scores during nasal anesthesia, nasal insertion/exsertion, UT-EGD, and overall tolerance were significantly lower in the meatuscopy group than sniff test group. Compared with the sniff tested patients, the meatuscopied patients had significantly lower epistaxis rates during insertion/exsertion, better visual capacity after decongestive anesthesia, and shorter total procedure time. A significantly higher proportion of the meatuscopied than sniff tested patients would like to receive the same procedure next time. Nasal discharge, nasal pain, epistaxis, and blowing out blood clots occurred significantly less frequent in the meatuscopy group than sniff test group. More sniff tested than meatuscopied patients had headache, delayed epistaxis, and sinusitis although they were not statistically significant. CONCLUSION: Selection of an optimal meatus insertion tract by an anterior meatuscopy causes lesser nasal pain, epistaxis, and post-procedural side effects in nasal anesthesia and UT-EGD than the conventional sniff test.

Overlap of Dyspepsia in Patients with Gastroesophageal Reflux Disease: Impact of Clinical, Metabolic, and Psychosocial Characteristics.

BACKGROUND: Gastroesophageal reflux disease (GERD) and dyspepsia are highly prevalent in the general population with significant symptom overlap, while the interaction between both remains poorly understood. AIM: To examine whether GERD overlapping dyspepsia would have an impact on clinical and psychological features as compared with GERD alone. METHODS: We performed a cross-sectional study in a GERD cohort (n = 868) that was previously recruited from a population-based GERD survey (n = 2752). We compared the clinical and psychological factors between patients with and without dyspeptic symptoms "epigastric pain or burning." All participants were evaluated with Reflux Disease Questionnaire score, Pittsburgh Sleep Quality Index score, Taiwanese Depression Questionnaire score, and State-Trait Anxiety Inventory score. Endoscopic findings were classified according to the Los Angeles classification. RESULTS: Among the GERD population, 107 subjects had overlapping "epigastric pain or burning" (GERD-D), and 761 did not have these symptoms (GERD alone). GERD-D subjects had more severe GERD symptoms and were more often associated with irritable bowel syndrome (IBS) (OR 3.54, 95% CI 1.92-6.52) as compared subjects with GERD alone. In addition, GERD-D subjects had lower quality of sleep (OR 1.11, 95% CI 1.01-1.21), higher depression (OR 1.06, 95% CI 1.02-1.10), lower blood pressure (OR 0.45, 95% CI 0.22-0.95), and higher serum total cholesterol levels (OR 2.78, 95% CI 1.36-5.67) than GERD alone. CONCLUSIONS: GERD-D subjects are characterized with worsening clinical symptoms as well as higher psychosocial, IBS, and metabolic comorbidities, but less erosive esophagitis. Our results indicate that clinical awareness of such overlapping condition would help optimize the management of GERD in clinical practice.

Sleep disturbance and enhanced esophageal capsaicin sensitivity in patients with gastroesophageal reflux disease.

BACKGROUND AND AIM: Esophageal infusion of capsaicin-containing red pepper sauce induced heartburn symptoms in patients with gastroesophageal reflux disease (GERD). We aimed to test the hypothesis whether sleep disturbance modulates esophageal sensitivity to capsaicin infusion in patients with GERD. METHODS: We enrolled 40 patients with their sleep quality measured by the Pittsburg Sleep Quality Index with > 5 indicating sleep disturbance. Esophageal sensation to capsaicin infusion was documented via measures of lag time to initial heartburn perception, heartburn intensity rating, and sensitivity score by esophageal infusion of capsaicin-containing red pepper sauce. Objective sleep measures were assessed by ambulatory actigraphy. RESULTS: We found 22 patients with sleep disturbance. The patients with sleep disturbance had shorter lag time to initial heartburn perception (P = 0.03) and greater sensory intensity rating (P = 0.02). The sensitivity score for capsaicin infusion was greater in patients with sleep disturbance when compared with those without sleep disturbance (P = 0.04). Actigraphy measures revealed that patients with sleep disturbance also had poor sleep efficiency (P = 0.04), longer average awakening time (P = 0.03), and greater total activity account (P = 0.04). The lag time for perceiving capsaicin infusion was positively correlated with total sleep time (r = 0.43, P = 0.03). CONCLUSIONS: We have shown that GERD patients with sleep disturbance have significantly enhanced heartburn perception to capsaicin infusion as compared with those with normal sleep. Our findings suggest that sleep disturbance is associated with esophageal hypersensitivity to capsaicin infusion in patients with GERD.

Effects of esophageal capsaicin instillation on acid induced excitation of secondary peristalsis in humans.

BACKGROUND/AIM: Esophageal instillation of capsaicin or hydrochloric acid enhances secondary peristalsis. Our aim was to investigate whether intra-esophageal capsaicin infusion can influence symptom perception and physiological alteration of secondary peristalsis subsequent to acid infusion. METHODS: Secondary peristalsis was induced by mid-esophagus injections of air in 18 healthy subjects. Two different sessions including esophageal infusion of hydrochloric acid (0.1 N) following pretreatment with saline or capsaicin-containing red pepper sauce were randomly performed at least one week apart. Symptoms of heartburn and secondary peristalsis were determined and compared between each study session. RESULTS: The intensity of heartburn symptom subsequent to acid infusion was significantly reduced after capsaicin infusion as compared with saline infusion (54 ± 3 vs 61 ± 3; P = 0.03). Capsaicin infusion significantly increased the threshold volume of secondary peristalsis to rapid air injections subsequent to esophageal acid infusion (8.0 ± 0.5 mL vs 4.4 ± 0.3 mL; P < 0.0001). The frequency of secondary peristalsis subsequent to acid infusion was significantly decreased after capsaicin infusion as compared to saline infusion (70% [60-82.5%] vs 80% [70-90%]; P = 0.03). Capsaicin infusion significantly decreased the pressure wave amplitude of secondary peristalsis subsequent to acid infusion during rapid air injections (90.6 ± 8.7 mmHg vs 111.1 ± 11.1 mmHg; P = 0.03). CONCLUSIONS: Capsaicin appears to desensitize the esophagus to acid induced excitation of secondary peristalsis in humans, which is probably mediated by rapidly adapting mucosal mechanoreceptors. High capsaicin-containing diet might attenuate normal physiological response to abrupt acid reflux by inhibiting secondary peristalsis.

Esophageal motor abnormalities in gastroesophageal reflux disorders.

Gastroesophageal reflux disease (GERD), a prevalent condition with multifactorial pathogenesis, involves esophageal motor dysmotility as a key contributing factor to its development. When suspected GERD patients have an inadequate response to proton-pump inhibitor (PPI) therapy and normal upper endoscopy results, high-resolution manometry (HRM) is utilized to rule out alternative diagnosis such as achalasia spectrum disorders, rumination, or supragastric belching. At present, HRM continues to provide supportive evidence for diagnosing GERD and determining the appropriate treatment. This review focuses on the existing understanding of the connection between esophageal motor findings and the pathogenesis of GERD, along with the significance of esophageal HRM in managing GERD patients. The International GERD Consensus Working Group introduced a three-step method, assessing the esophagogastric junction (EGJ), esophageal body motility, and contraction reserve with multiple rapid swallow (MRS) maneuvers. Crucial HRM abnormalities in GERD include frequent transient lower esophageal sphincter relaxations, disrupted EGJ, and esophageal body hypomotility. Emerging HRM metrics like EGJ-contractile integral and innovative provocative maneuver like straight leg raise have the potential to enhance our understanding of factors contributing to GERD, thereby increasing the value of HRM performed in patients who experience symptoms suspected of GERD.