Sohrab Rahimi Naini

Response of the Upper Esophageal Sphincter to Esophageal Distension Is Affected by Posture, Velocity, Volume, and Composition of the Infusate

BACKGROUND & AIMS Studies of the pressure response of the upper esophageal sphincter (UES) to simulated or spontaneous gastroesophageal reflux have shown conflicting results. These discrepancies could result from uncontrolled influence of variables such as posture, volume, and velocity of distension. We characterized in humans the effects of these variables on UES pressure response to esophageal distension. METHODS We studied 12 healthy volunteers (average, 27 ± 5 years old; 6 male) using concurrent esophageal infusion and high-resolution manometry to determine UES, lower esophageal sphincter, and intraesophageal pressure values. Reflux events were simulated by distal esophageal injections of room temperature air and water (5, 10, 20, and 50 mL) in individuals in 3 positions (upright, supine, and semisupine). Frequencies of various UES responses were compared using χ(2) analysis. Multinomial logistical regression analysis was used to identify factors that determine the UES response. RESULTS UES contraction and relaxation were the overriding responses to esophageal water and air distension, respectively, in a volume-dependent fashion (P < .001). Water-induced UES contraction and air-induced UES relaxation were the predominant responses among individuals in supine and upright positions, respectively (P < .001). The prevalence of their respective predominant response significantly decreased in the opposite position. Proximal esophageal dp/dt significantly and independently differentiated the UES response to infusion with water or air. CONCLUSIONS The UES response to esophageal distension is affected by combined effects of posture (spatial orientation of the esophagus), physical properties, and volume of refluxate, as well as the magnitude and rate of increase in intraesophageal pressure. The UES response to esophageal distension can be predicted using a model that incorporates these factors.

Impaired Upper Esophageal Sphincter Reflexes in Patients With Supraesophageal Reflux Disease

BACKGROUND & AIMS Normal responses of the upper esophageal sphincter (UES) and esophageal body to liquid reflux events prevent esophagopharyngeal reflux and its complications, however, abnormal responses have not been characterized. We investigated whether patients with supraesophageal reflux disease (SERD) have impaired UES and esophageal body responses to simulated reflux events. METHODS We performed a prospective study of 25 patients with SERD (age, 19-82 y; 13 women) and complaints of regurgitation and supraesophageal manifestations of reflux. We also included 10 patients with gastroesophageal reflux disease (GERD; age, 32-60 y; 7 women) without troublesome regurgitation and supraesophageal symptoms and 24 healthy asymptomatic individuals (controls: age, 19-49 y; 13 women). UES and esophageal body pressure responses, along with luminal distribution of infusate during esophageal rapid and slow infusion of air or liquid, were monitored by concurrent high-resolution manometry and intraluminal impedance. RESULTS A significantly smaller proportion of patients with SERD had UES contractile reflexes in response to slow esophageal infusion of acid than controls or patients with GERD. Only patients with SERD had abnormal UES relaxation responses to rapid distension with saline. Diminished esophageal peristaltic contractions resulted in esophageal stasis in patients with GERD or SERD. CONCLUSIONS Patients with SERD and complaints of regurgitation have impaired UES and esophageal responses to simulated liquid reflux events. These patterns could predispose them to esophagopharyngeal reflux.

Prevention of esophagopharyngeal reflux by augmenting the upper esophageal sphincter pressure barrier

Incompetence of the upper esophageal sphincter (UES) is fundamental to the occurrence of esophagopharyngeal reflux (EPR), and development of supraesophageal manifestations of reflux disease (SERD). However, therapeutic approaches to SERD have not been directed to strengthening of the UES barrier function. Our aims were to demonstrate that EPR events can be experimentally induced in SERD patients and not in healthy controls, and ascertain if these events can be prevented by application of a modest external cricoid pressure.

Characterization of the upper esophageal sphincter response during cough.

BACKGROUND Vagal reflex initiated by esophageal stimulation and microaspiration can cause chronic cough in patients with gastroesophageal reflux disease (GERD). By raising intraabdominal pressure,cough can, in turn, predispose to GERD. The role of the upper esophageal sphincter (UES)in preventing esophagopharyngeal reflux during coughing is not well known. The aim of this study was to evaluate the UES response during coughing. METHODS We studied 20 healthy young (10 women; age, 27 ± 5 years) and 15 healthy elderly(nine women; age, 73 ± 4 years) subjects. Hard and soft cough-induced pressure changes in the UES, distal esophagus, lower esophageal sphincter, and stomach were determined simultaneously using high-resolution manometry and concurrent acoustic cough recordings. RESULTS Resting UES pressure was significantly higher in the young compared with the elderly subjects (42 ± 14 mm Hg vs 24 ± 9 mm Hg; P < .001). Cough induced a UES contractile response in all subjects. Despite lower UES resting pressures in the elderly subjects, the maximum UES pressure during cough was similar between the young and the elderly subjects (hard cough, 230 ± 107 mm Hg vs 278 ± 125 mm Hg, respectively; soft cough, 156 ± 85 mm Hg vs 164 ± 119 mm Hg, respectively; P not significant for both). The UES pressure increase over baseline during cough was significantly higher than that in the esophagus, lower esophageal sphincter, and stomach for both groups ( P < .001). CONCLUSIONS Cough induces a rise in UES pressure, and this response is preserved in elderly people. A cough-induced rise in UES pressure is significantly higher than that in the esophagus and stomach,thereby providing a barrier against retrograde entry of gastric contents into the pharynx.

Tu1765 Regurgitation Can Indicate Either True Esophago-Pharyngeal Reflux (EPR) Event or Upper Esophageal Sphincter (UES) and Sub-Sphincter Proximal Esophageal Acid Exposure

In prior studies we found that esophageal acid exposure caused a small decrease in airway diameter, an increase in tracheobronchial mucus secretion, and a decrease in mucociliary transport rate. However, the store of mucus is not large and can easily be depleted, therefore, we hypothesized that mucus production may be under physiological control. AIM: To determine whether a physiological stimulus can affect mucus production and to investigate the mechanism of this effect. METHODS: Sixteen cats were anesthetized using alphachloralose. The esophagus was ligated 3-4 cm from the UES and the esophagus proximal and distal to the ligation was cannulated. Either the proximal (N=8) or distal (N=8) esophagus was perfused using 0.1N HCl for 30 min followed by 30 min of PBS while the opposite esophageal segment was perfused with PBS for 60 min. The trachea was excised, fixed, sliced at 5μ, and stained with Periodic Acid Schiff (PAS)-Alcian Blue (AB) at pH 1.0. The areas of neutral (PAS-positive) and acidic (AB-positive) mucosubstances in the epithelial and submucosal mucous glands of the trachea adjacent to the proximal and distal cervical segments of esophagus perfused were quantified using Image J software. RESULTS: We found that the primary type of mucous of the epithelial and submucosal mucous cells was AB-positive and PAS-positive, respectively. Acid exposure of either esophageal segment caused a greater total and PAS-positive mucous content of the submucosal cells adjacent to the HCl-administered esophagus than adjacent to the PBS-administered esophagus (Table). CONCLUSIONS: The primary types of mucosubstances of the tracheal epithelial and submucosal cells are acidic and neutral respectively. Esophageal acid exposure increases mucus production of neutral mucosubstances of the tracheal submucosa probably through the previously identified local direct neural connection between the esophagus and trachea. We hypothesize that this pathway is part of the innate tracheal defense mechanism which prepares the trachea for acid exposure due to gastric reflux. Effects of HCl and PBS on Tracheal Mucous Content

480 Efficacy of a Novel “UES Assist Device” in Management of Supraesophageal Complications of Reflux Disease: the Results of a Limited Clinical Trial

Background:Management of supraesophageal reflux disease complications of poses a significant clinical challenge. Acid suppressive therapy does not prevent volume refluxate into the pharynx and as such in a substantial percentage of these patients outcome of medical management has been disappointing. The efficacy of a novel “UES Assist Device” in preventing of simulated pharyngeal reflux in experimental setting have been recently reported. (Shaker et al. DDW 2010) The aim of the present study was to test the efficacy of the “UES Assist Device” in management of supraesophageal symptoms of reflux disease in a clinical trial. Method: We studied 14 patients with a variety of supraesophageal symptoms most notably chronic cough, excess phlegm and throat clearing referred from GI clinic in our institution. Participants filled out a detailed symptom questionnaire at baseline and following application of the device with randomly applied therapeutic and sub-therapeutic pressure assist. Symptoms were quantified using a 5-pont Likert scale. Each therapeutic modality was tested randomly for 7 days. Result: All patients tolerated the device well and completed the study. There were no complications or complaints for the use of the device. The global symptoms severity and impact score for therapeutic and sub-therapeutic pressure assist was significantly lower than that of the baseline. In addition, therapeutic pressure assist resulted in a significantly lower symptom severity compared to sub-therapeutic pressure assist (p=0.003 ANOVA) . (Figure) Furthermore, therapeutic pressure assist significantly decreased the most bothersome symptom compared to sub-therapeutic pressure assist (p<0.05). Conclusion: “UES Assist Device” is safe and effective in management of supraesophageal complications of reflux disease.

Tu1104 Objective Identification of Common Daily Activities by Their Manometric Signatures Using Ambulatory Pressure Recording

Background: During pathological assessment of esophageal biopsies several histological features characterizing the diagnosis of microscopic esophagitis [basal cell hyperplasia (BCH), papillary enlongation (PE), dilated intercellular spaces (DIS) and epithelial neutrofilic/eosinophilic infiltration (Neu/Eos)] can be assessed. Limited data are available about the single contribution of these histological abnormalities on the diagnosis of GERD and its related mucosal integrity in well-defined patients with reflux disease. Aim: To determine whether these histological features contribute differently to the diagnosis GERD and to the impairment of mucosal integrity as expressed by baseline impedance (BI) levels. Methods:One hundred and four consecutive patients with typical reflux symptoms underwent upper endoscopy and multiple biopsies were taken at Z-line and 2 cm above it, in order to assess the presence and severity of BCH, PE, DIS and Neu/Eos [0 (absent), 1 (mild), and 2 (marked)]. Within 3 days from endoscopy, patients underwent impedance-pH testing off-therapy. During manual analysis of the impedance-pH tracings, we measured the esophageal acid expsosure time (AET) over the 24 hours and the total (acid + non-acid) number of impedance-detected reflux episodes. We evaluated BI values at 3 and 5cm above the LES, during the overnight rest, for at least 30 minutes after excluding swallows and reflux induced changes. Twenty healthy volunteers (HVs; 11F/9M; mean age 44) who underwent the same procedures were also enrolled as controls. Results:We included 85 patients with an endoscopic/impedancepH diagnosis of GERD (45F/40M; mean age 46) who had esophageal mucosal breaks at upper endoscopy or an abnormal esophageal acid exposure or a normal esophageal acid exposure but a positive reflux-symptom association at impedance-pH testing. Among these patients, BI values at both 3 and 5 cm above the LES positively correlated with the esophageal AET (r2=0.2033, P<0.001 and r2=0.1859, P<0.001, respectively) and the number of impedance-detected reflux episodes (r2=0.1373, P<0.001 and r2=0,1526, P<0.001, respectively). Moreover, as shown in the Table, BCH and DIS were the lesions more significantly correlated with the endoscopic/impedance-pH diagnosis of GERD. No significant correlation was observed between BI values and impedance-pH parameters or histological lesions in HVs (p=ns). Conclusions: BCH and DIS contribute more than PE and Eos/Neu to the endoscopic/ impedance-pH diagnosis of GERD. Moreover, the same lesions seem to play a greater role than PE and Eos/Neu in determining mucosal integrity impairment as expressed by BI values in GERD patients. Overall, BCH and DIS can be considered the histological markers requiring more carefully evaluation during pathologic assessment in order to help the diagnosis of GERD. Correlation of BI levels with ME histologic features

Sa1454 Correlation of the Threshold Volume to Trigger Reflexive Pharyngeal Swallow With the Hypopharyngeal Safe Volume in Awake State Can Predict Aspiration During Sleep

BACKGROUND: Cough and swallowing are important protective mechanisms that maintain the integrity of the aero-digestive tract across the age spectrum. Premature neonates commonly experience swallowing and breathing problems. Consequently, anterograde or retrograde aspiration is a frequent concern in neonates with chronic lung disease such as bronchopulmonary dysplasia (BPD). AIMS: Our aims were to define the cough-initiating and subsequent post-tussive mechanisms that restore aero-digestive normalcy (defined as return of respiratory rhythm to baseline along with esophageal quiescence) in human premature infants suffering from BPD. METHODS: Ten premature neonates (born at 25.5 ± 0.6 wks gestation, studied at 42.2 ± 1.2 wks post-menstrual age), diagnosed with BPD underwent concurrent pharyngo-esophageal manometry, respiratory inductance plethysmography (using Respitrace) and nasal air flow (using thermistor) methods to determine the relationships between esophageal motility and respiratory phases using a specially designed manometric catheter with upper and lower esophageal sphincter (UES and LES) sleeves and 5 recording pressure ports from pharynx, proximal-, middle-, and distalesophagus, and stomach. Cough was recognized as forceful exhalation preceded by deep inhalation on the respiratory waveforms along with audible cough marked during the study. The dynamic characteristics were analyzed preceding and following cough events defined by manometry and Respitrace. RESULTS: 1) Cough initiating mechanisms during 59 cough episodes are shown (Table). 2) Post-tussive mechanisms that restored aero-digestive normalcy were primary peristalsis in 81.4% (48/59), secondary peristalsis in 15.3 % (9/59), and not recognizable in 3.4 % (2/59). CONCLUSIONS: 1) In premature neonates with BPD, non-propagating swallows and UES contractile reflexes are the dominant reasons for the origin of the cough reflex, indicating the majority of cough events have upper aero-digestive origins. 2) Primary peristalsis is the most important clearance mechanism for post-tussive restoration of respiratory normalcy and pharyngo-esophageal quiescence. 3) These phenomena underscore the importance of postnatal development of esophagus-airway reciprocal communications mediated by Glossopharyngeal and Vagal nerves in human premature neonates with BPD. *Supported by PPG-PO1 DK 068051 Mechanisms triggering cough in neonates.