Jamal O. Hayat

Pepsin in saliva for the diagnosis of gastro-oesophageal reflux disease

Objective Current diagnostic methods for gastro-oesophageal reflux disease (GORD) have moderate sensitivity/specificity and can be invasive and expensive. Pepsin detection in saliva has been proposed as an ‘office-based’ method for GORD diagnosis. The aims of this study were to establish normal values of salivary pepsin in healthy asymptomatic subjects and to determine its value to discriminate patients with reflux-related symptoms (GORD, hypersensitive oesophagus (HO)) from functional heartburn (FH). Design 100 asymptomatic controls and 111 patients with heartburn underwent MII-pH monitoring and simultaneous salivary pepsin determination on waking, after lunch and dinner. Cut-off value for pepsin positivity was 16 ng/mL. Patients were divided into GORD (increased acid exposure time (AET), n=58); HO (normal AET and + Symptom Association Probability (SAP), n=26) and FH (normal AET and—SAP, n=27). Results 1/3 of asymptomatic subjects had pepsin in saliva at low concentration (0(0–59)ng/mL). Patients with GORD and HO had higher prevalence and pepsin concentration than controls (HO, 237(52–311)ng/mL and GORD, 121(29–252)ng/mL)(p<0.05). Patients with FH had low prevalence and concentration of pepsin in saliva (0(0–40) ng/mL). A positive test had 78.6% sensitivity and 64.9% specificity for diagnosis of GORD+HO (likelihood ratio: 2.23). However, one positive sample with >210 ng/mL pepsin suggested presence of GORD+HO with 98.2% specificity (likelihood ratio: 25.1). Only 18/84 (21.4%) of GORD+HO patients had 3 negative samples. Conclusion In patients with symptoms suggestive of GORD, salivary pepsin testing may complement questionnaires to assist office-based diagnosis. This may lessen the use of unnecessary antireflux therapy and the need for further invasive and expensive diagnostic methods.

Objective Detection of Esophagopharyngeal Reflux in Patients With Hoarseness and Endoscopic Signs of Laryngeal Inflammation

Goals: We aimed to quantify pharyngeal exposure to gastric contents in patients diagnosed with reflux-related hoarseness and healthy controls using new diagnostic techniques. Background: Hoarseness with typical signs on laryngoscopy is commonly thought to be caused by esophagopharyngeal reflux. New methods are proposed to assess pharyngeal exposure to gastric contents. They are suggested to measure: (1) liquid or mixed gas-liquid acid and nonacid reflux with impedance pH, (2) aerosolized acid reflux (Dx-pH measuring system), and (3) pepsin in the saliva. Study: Twenty-one patients with hoarseness and positive laryngoscopy and 10 controls underwent simultaneous impedance pH, Dx-pH monitoring, and saliva pepsin sampling (5 samples in 24 h). Results: Of the 21 patients, 10 had impedance pH–detected reflux plus at least 1 other test positive. These patients were more likely to have symptomatic relief after proton pump inhibitor therapy. Three of the 21 patients had all 3 tests positive and 4 had all tests negative. None of the controls had impedance pH–detected reflux. Two controls had a positive Dx-pH “RYAN score” and 1 control had >1 saliva sample positive for pepsin. Only 11% of Dx-pH drops to pH<4, 15% pH drops to pH<5, and 10% of pH drops to pH<5.5 coincided with impedance pH–detected reflux in the esophageal body. Positive pepsin saliva samples were preceded by more reflux events [3 (range, 0 to 10)] in the previous 60 minutes than negative samples [0 (range, 0 to 7)] (P<0.0001). Conclusion: A subgroup of patients with hoarseness (10/21) had objective detection of the esophagopharyngeal reflux. We propose that these patients are more likely to benefit from further intense antireflux therapy. Detection of pepsin in the saliva may be a useful screening tool in these patients.

Objective Assessment of Aerophagia During Meals in Normal Subjects and Patients With Post-Prandial Bloating and Belching

Introduction Many patients attending GI physiology units for assessment of dysphagia and GORD also complain of postprandial bloating and/or belching. Excessive fasting aerophagia has been recently described in patients with severe continuous bloating and belching. Exaggerated air swallowing during meals might be more relevant for postprandial symptoms but, thus far, objective assessment of prandial aerophagia and normal values are lacking. Oesophageal impedance can detect air swallowing. We aimed to quantify aerophagia during meals in asymptomatic subjects and patients with postprandial bloating and belching. Methods We assessed aerophagia during meals using ambulatory impedance-pH monitoring in 39 healthy, asymptomatic controls (from the US-Belgian MII-pH Normal value study, Shay et al . 2004; mean age in original study 39, range 22–62) to establish normal 95% confidence intervals. We identified 38 patients (mean age 43, range 17–74) with postprandial bloating and/or belching who attended the GI physiology unit for assessment of dysphagia or GORD as primary symptoms. Mealtime air swallows were visually identified when swallows were associated with antegrade flow and fast impedance increase (at least 3000 Ω from baseline) in the most distal recording segment. A score of air swallows/10 min mealtime was calculated for each subject. In patients with mealtime exaggerated air swallowing (above 95th percentile of normal values) we examined for evidence of concomitant fasting aerophagia. Results The 95% percentile range of mealtime aerophagia in normal subjects was 6.8 to 9.4 episodes/10 min, mean 8.1. Patients had significantly higher mealtime air swallowing rates than controls (mean 11.8 episodes/10 min, SEM 1.0, p = 0.003 ). There was no significant difference between predominant bloating and belching subgroups. Only 4 of 23 patients with exaggerated mealtime air swallowing had concomitant fasting aerophagia. Conclusion We established normal values of mealtime air swallowing using oesophageal impedance. Patients with postprandial bloating and/or belching exhibit increased aerophagia during meals. Most of these patients do not have fasting aerophagia. Exaggerated air swallowing during meals can now be objectively detected and biofeedback techniques can be attempted to modify such behaviour as a potential therapeutic strategy for these patients with functional GI symptoms.

Tu1096 Postprandial Pepsin in Saliva in Healthy Subjects and Patients With GERD. Relationship With Postprandial Reflux

BACKGROUND: The Controlled Attenuation Parameter (CAP) is promising tool for the noninvasive detection of hepatic steatosis using a process based on transient elastography. The relationship between CAP and erosive esophagitis (EE) was investigated. METHODS: A total of 1,139 subjects from a health promotion center at Yonsei University Health System, Seoul, Korea were enrolled. Esophagogastroduodenoscopy (EGD) and liver transient elastography were done in all participants. The association between EE and hepatic steatosis was estimated with odds ratios (ORs) and 95% confidence intervals (CIs). Blood pressure, body mass index (BMI), skeletal muscle mass, body fat mass, percent body fat, waist-hip ratio (WHR), serum total cholesterol, high-density lipoprotein cholesterol (HDL-C), lowdensity lipoprotein cholesterol (LDL-C), triglyceride (TG), fasting glucose, HbA1c were compared between individuals with and without EE. Risk factors for EE were evaluated by multivariate logistic regression. Severity of hepatic steatosis by CAP score was defined as S0 (less than 270 dB/m), S1 (270-299 dB/m), S2 (300-319 dB/m), and S3 (≥300 dB/m). RESULTS:: The prevalence of erosive esophagitis was 6.6% (75/1,139). Severity of hepatic steatosis and was positively associated with prevalence (3.8% in S0, 12.5% in S1, 18.4% in S3, and 27.8% in S4, p<0.001), as well as severity of erosive esophagitis (p<0.001). Male gender, high CAP score, high waist-hip ratio, high diastolic blood pressure, high BMI, high TG level and hiatus hernia was associated with EE (p<0.001 for each factor). In a multivariate analysis, male gender (OR, 2.45, 95% CI, 1.37-4.38, p= 0.003), central obesity (OR, 1.41, 95% CI, 1.02-1.91, p= 0.024), hiatus hernia (OR, 3.79, 95% CI, 1.05-13.59, p=0.031), and hepatic steatosis were significantly associated with erosive esophagitis. The OR of EE for hepatic steatosis was 3.08 (95% CI, 1.68-5.67) for S1, 5.77 (95% CI, 2.55-13.41) for S2, and 8.79 (95%CI, 4.32-17.85) for S3, compared with participants with S0 (p<0.001) CONCLUSION:: Hepatic steatosis is associated with increased risk and severity of erosive esophagitis. In addition, male gender, central obesity and hiatus hernia were also positively associated with erosive esophagitis.

Tu1840 Gastro-Esophageal Reflux Disease, Esophageal Dysmotility and Gastric Emptying in Patients Before and After Laparoscopic Sleeve Gastrectomy

G A A b st ra ct s Barrett patients than in controls and was similar to GERD patients (table 1). In vitro transepithelial electrical resistance of biopsies was also lower in Barrett than in controls and similar to GERD patients, while in vitro transepithelial fluorescein flux was higher in GERD and Barrett patients compared to controls, both with a trend towards significance (table 1). Conclusions: The hypersensitivity to acid observed in GERD patients without Barrett is not present in patients with Barretts esophagus. Mucosal integrity is, however, equally impaired in patients with Barrett and GERD, indicating that a preserved esophageal mucosal barrier to acid is not an explanation for the lack of acid hypersensitivity in patients with Barretts esophagus. Table 1. Esophageal sensitivity and mucosal integrity parameters

Intermittent Esophageal Hypotensive Peristalsis Re-Assessed With Multiple Rapid Swallowing

We recently proposed the usefulness of the house musk shrew (Suncus murinus ) as a model animal for motilin study because this animal produces a motilin family peptide and shows the phasic interdigestive gastric contraction. This gastric motor contraction includes phase I, phase II and phase III contractions as found in dogs and humans. In the DDW 2010, we reported that cumulative ghrelin administration and pretreatment with a low dose of motilin (10−10 M) synergistically induced gastric contraction in a dose-dependent manner, suggesting that ghrelin is involved in the migrating motor complex (MMC) and has a complementary effect with motilin. To clarify the effects of these family peptides on each phase in the MMC, we administrated an antagonist of motilin or ghrelin into a force transducer-sutured freemoving suncus. At 10-20 min after the beginning of phase II contraction, MA-2029 (1 mg kg−1 h−1, motilin receptor antagonist) or saline was continuously infused for 2 h, and we found that phase II-like contraction was prolonged and that no phase III contraction occurred during the infusion of MA-2029. The duration from the start of infusion of the motilin antagonist and phase III contraction was significantly longer (182 ± 12 min) than that in controls (71 ± 6 min, P<0.05). These results indicate that motilin has no effect on continuing phase II contraction but is essential for induction of phase III contraction. The frequencies of phasic contraction with saline treatment and MA-2029 treatment were almost the same in phase II (saline: 14 ± 0.7 min−1, MA-2029: 13 ± 0.7 min−1). Although bolus administration of motilin (300 ng kg−1 i.v.) significantly induced phase III-like contraction in the control suncus In Vivo, during the infusion of MA-2029, motilin administration (300 ng kg−1) did not evoke phase III-like contraction. On the other hand, continuous infusion of D-Lys3GRHP6 (6 mg kg−1 h−1, ghrelin receptor antagonist) for 2 h inhibited phase II contraction and completely suppressed phase III contraction, and phase II contraction restarted after the end of infusion. The results of this study together with the results of our previous study showing that ghrelin administration (0.1, 0.2 μg kg−1 min−1 for 10 min i.v.) in phase II of MMC significantly enhanced gastric contraction in a dose-dependent manner indicated that MMC in the free-moving suncus stomach is coordinated by endogenous motilin and ghrelin. Phase II contraction may be initiated by endogenous ghrelin, and subsequent increase in motilin induces following phase III contraction.