Analysis of Spontaneous Gastroesophageal Reflux and Esophageal Acid Clearance in Patients with Reflux Esophagitis

To characterize gastroesophageal reflux episodes and esophageal acid clearance in patients with reflux esophagitis, we obtained 12-hour overnight esophageal pH and manometry recordings in 20 patients with macroscopic reflux esophagitis and in 15 healthy volunteers. Compared to the control subjects, the patients had less pressure in the lower esophageal sphincter (LES) and higher rates of reflux, acid clearance time, and esophageal acid exposure. However, many patients had normal values for one or more of these variables. Transient LES relaxation accounted for 96% of reflux episodes in control subjects and 60% in patients. The remaining 40% of reflux episodes in patients occurred as stress or free reflux. In the control subjects, only one reflux episode occurred during estimated sleep. Of 22 reflux episodes during estimated sleep in patients, most were associated with low basal LES pressure. During esophageal acid clearance, the major esophageal motor event was swallow-induced peristalsis rather than secondary peristalsis. We conclude that esophagitis patients have lower LES pressures, more reflux episodes, impaired esophageal acid clearance, and more esophageal exposure to acid than control subjects. Individual patients, however, exhibit heterogeneous abnormalities with respect to these variables. Transient LES relaxation is the major mechanism of gastroesophageal reflux in both patients and healthy subjects.     

The lower esophageal sphincter

The lower esophageal sphincters (LES) together with the crural diaphragm are the major antireflux barriers protecting the esophagus from reflux of gastric content. However, reflux of gastric contents into the esophagus is a normal phenomenon in healthy individuals occurring primarily during episodes of transient lower esophageal sphincter relaxation (TLESR), defined as LES relaxation in the absence of a swallow. Transient lower esophageal sphincter relaxation is also the dominant mechanism of pathologic reflux in gastroesophageal reflux disorder (GERD) patients. Frequency of TLESR does not differ significantly between healthy individuals and those with GERD, but TLESRs are more likely to be associated with acid reflux in GERD patients. Understanding the mechanisms responsible for elicitation of a TLESR, using recently introduced novel technology is an area of intense interest. Pharmacologic and non‐pharmacologic manipulation of receptors involved in the control of TLESR has recently emerged as a potential target for GERD therapy.     

Mechanisms of gastroesophageal reflux in children with sequelae of birth asphyxia

Patterns of childhood gastroesophageal reflux (GER) have been studied extensively; however, the mechanisms underlying its occurrence in neurologically impaired children (NIC) are poorly understood. Concurrent esophageal manometry and pH monitoring was conducted in 10 un-operated children (7 male; mean age: 59.5 months) with sequelae birth asphyxia and esophagitis. Reflux episodes were scored when esophageal pH decreased to <4 for at least 5s. When the rate of decrease of lower esophageal sphincter (LES) pressure was >1mmHg/s, the decrease of LES pressure was defined as LES relaxation. The time relationship of the pharyngeal manometric swallowing signal to LES relaxation onset was then evaluated in order to distinguish between LES relaxations associated with swallowing (type II or III, associated with one or more swallows, respectively) and those that occurred independently of swallowing (type I). Results: Esophageal manometry and pH monitoring were conducted for a mean duration of 91.5min. Basal LES pressure averaged (+/-SD) 9.2+/-4.8mmHg; in 4 of 10 patients (40%) the LES pressure was largely undetectable, varying between 0 and 2mmHg. Mean LES pressure was inversely correlated with age (r=0.7, P=0.02). The total number of reflux episodes/h averaged 32.1+/-12.1 LES pressure reached 0mmHg in 98% of reflux episodes. Type I LES relaxations were present in 3.15+/-1.1 reflux episodes/h, whereas type II LES relaxation occurred in 2.3+/-2.4 episodes/h. Acid reflux episodes appeared during absent basal LES tone periods, without phasic LES relaxations, in 74%. Conclusions: Absent basal LES tone is the main mechanism of GER in a subgroup of NIC, especially in older children. Transient LES relaxation, the most common known event associated with acid reflux in neurologically normal children, seems to precede a minority of reflux events in NIC.     

Relationship Between Gastroesophageal Reflux and Symptoms in Patients Referred for Ambulatory pH Monitoring

Ambulatory pH monitoring is regarded as the most objective means of detecting and quantifying gastroesophageal reflux. Nevertheless, the relationship between symptoms and distal esophageal acid exposure is unclear, especially in patients with atypical reflux symptoms or noncardiac chest pain. The aim of this study was to explore the relationship between symptoms and the indices of gastroesophageal reflux currently used. We examined 100 consecutive, unselected patients referred for ambulatory pH monitoring with suspected symptomatic gastroesophageal reflux (n = 65) or unexplained noncardiac chest pain (n = 35). A symptom-reflux association (SRA) was defined as the percentage of episodes of pain, or heartburn, during pH monitoring that were reported within 5 minutes of a gastroesophageal reflux event (pH fall to < 4). The two most sensitive predictors of symptomatic reflux (defined as a SRA < 50%) were the frequency of erect reflux episodes per hour (sensitivity 90%, specificity 77%, and accuracy 85%) and the erect reflux time (sensitivity 61%, specificity 93%, and accuracy 75%). To identify gastroesophageal reflux as a cause of symptoms, it is important to seek a temporal relationship between symptoms and reflux events. Reliance on acid exposure times alone will result in "false negative" diagnoses in some patients with symptomatic reflux who do not have excess reflux.     

Mechanism of gastroesophageal reflux in patients with obstructive sleep apnea syndrome

Background It has been reported that the prevalence of gastroesophageal reflux (GER) disease is high in patients with obstructive sleep apnea (OSA). End‐inspiratory intra‐esophageal pressure decreases progressively during OSA, which has been thought to facilitate GER in OSA patients. The aim of our study was to clarify the mechanisms of GER during sleep (sleep‐GER) in OSA patients. Methods Eight OSA patients with reflux esophagitis (RE), nine OSA patients without RE, and eight healthy controls were studied. Polysomnography with concurrent esophageal manometry and pH recording were performed. Key Results Significantly more sleep‐GER occurred in OSA patients with RE than without RE or in controls (P < 0.05). The severity of OSA did not differ between OSA patients with RE and without RE. Sleep‐GER was mainly caused by transient lower esophageal sphincter relaxation (TLESR), but not by negative intra‐esophageal pressure during OSA. During OSA gastroesophageal junction pressure progressively increased synchronous to intra‐esophageal pressure decrease. OSA patients had significantly more TLESR events during sleep related to preceding arousals and shallow sleep, but the number of TLESR events was not related to RE. Conclusions & Inferences In OSA patients, sleep‐GER was mainly caused by TLESR, but not by negative intra‐esophageal pressure due to OSA.     

Gastroesophageal and laryngopharyngeal reflux profiles in patients with obstructive sleep apnea/hypopnea syndrome as determined by combined multichannel intraluminal impedance-pH monitoring

Background The profiles of gastroesophageal reflux (GER) and laryngopharyngeal reflux (LPR) in patients with obstructive sleep apnea/hypopnea syndrome (OSAHS) have never been explored. The aim of the study was to investigate the reflux profile in OSAHS patients. Methods Consecutive snoring out‐patients suspected with having OSAHS and 20 healthy volunteers were included. All subjects underwent simultaneous 24‐h combined multichannel intraluminal impedance–pH (MII–pH) monitoring and polysomnography. Obstructive sleep apnea/hypopnea syndrome was defined when the apnea/hypopnea index was over 5. Stepwise multiple logistic regression analysis was performed to determine the predictor for OSAHS. Key Results Fifty‐three patients were included, 37 with and 16 without OSAHS. The prevalence of reflux symptoms was similar between OSAHS (35.1%) and non‐OSHAS (37.5%) patients. More OSAHS patients, compared with non‐OSAHS patients and healthy volunteers, had pathologic acid GER, nocturnal acid GER, and prolonged acid clearance (P < 0.001). However, no difference in non‐acid reflux episodes was observed among the three groups. Laryngopharyngeal reflux was detected in 51.4%, 43.8%, and 35.0% of OSAHS, non‐OSAHS, and healthy volunteers, respectively (P = 0.034). In OSAHS patients, there was no difference in the sleep parameters between patients with and without LPR. Body mass index was the only predictor of OSAHS in the regression analysis. Conclusions & Inferences OSAHS patients have more pathologic acid GER and prolonged acid clearance than non‐OSAHS patients whereas non‐acid reflux was similar between the two groups. However, BMI, not GER, is the only independent predictor for OSAHS. Laryngopharyngeal reflux occurs in more than half of OSAHS patients despite no significant association with OSAHS.     

Short-term electrical stimulation of the lower esophageal sphincter increases sphincter pressure in patients with gastroesophageal reflux disease

Background Electrical stimulation (ES) of the lower esophageal sphincter (LES) increases resting LES pressure (LESP) in animal models. Our aims were to evaluate the safety of such stimulation in humans, and test the hypothesis that ES increases resting LESP in patients with gastroesophageal reflux disease (GERD). Methods A total of 10 subjects (nine female patients, mean age 52.6 years), with symptoms of GERD responsive to PPIs, low resting LES pressure, and abnormal 24‐h intraesophageal pH test were enrolled. Those with hiatal hernia >2 cm and/or esophagitis >Los Angeles Grade B were excluded. Bipolar stitch electrodes were placed longitudinally in the LES during an elective laparoscopic cholecystectomy, secured by a clip and exteriorized through the abdominal wall. Following recovery, an external pulse generator delivered two types of stimulation for periods of 30 min: (i) low energy stimulation; pulse width of 200 μs, frequency of 20 Hz and current of 5–15 mA (current was increased up to 15 mA if LESP was less than 15 mmHg), and (ii) high energy stimulation; pulse width of 375 ms, frequency of 6 cpm, and current 5 mA. Resting LESP, amplitude of esophageal contractions and residual LESP in response to swallows were assessed before and after stimulation. Symptoms of chest pain, abdominal pain, and dysphagia were recorded before, during, and after stimulation and 7‐days after stimulation. Continuous cardiac monitoring was performed during and after stimulation. Key Results All patients were successfully implanted nine subjects received high frequency, low energy, and four subjects received low frequency, high energy stimulation. Both types of stimulation significantly increased resting LESP: from 8.6 mmHg (95% CI 4.1–13.1) to 16.6 mmHg (95% CI 10.8–19.2), P < 0.001 with low energy stimulation and from 9.2 mmHg (95% CI 2.0–16.3) to 16.5 mmHg (95% CI 2.7–30.1), P = 0.03 with high energy stimulation. Neither type of stimulation affected the amplitude of esophageal peristalsis or residual LESP. No subject complained of dysphagia. One subject had retrosternal discomfort with stimulation at15 mA that was not experienced with stimulation at 13 mA. There were no adverse events or any cardiac rhythm abnormalities with either type of stimulation. Conclusions & Inferences Short‐term stimulation of the LES in patients with GERD significantly increases resting LESP without affecting esophageal peristalsis or LES relaxation. Electrical stimulation of the LES may offer a novel therapy for patients with GERD.     

Gastrointestinal functioning during sleep: a new horizon in sleep medicine

A body of clinical and research literature is accumulating suggesting that there are significant alterations in gastrointestinal functioning during sleep, as well as sleep complaints and disorders in patients suffering from gastrointestinal disease. This review addresses the clinical applications of some basic alterations in gastrointestinal functioning during sleep, with a particular focus on gastroesophageal reflux disease and functional bowel disorders. Recent studies have shown that gastroesophageal reflux during sleep results in a marked prolongation of esophageal acid clearance time, and consequent mucosal damage. Data are reviewed which suggest that the more serious complications of gastroesophageal reflux, e.g. esophagitis and the extra-esophageal complications of reflux such as the exacerbation of bronchial asthma, laryngopharyngitis, and pulmonary aspiration are the result of sleep-related gastroesophageal reflux. Recent studies have also shown that patients with functional bowel disorder (e.g. irritable bowel syndrome and dyspepsia) have a high incidence of sleep complaints as well as abnormalities of autonomic functioning. Recent studies have shown that the measurement of autonomic functioning during sleep can differentiate the patients with functional bowel disorders from normal controls. The continued study of gastrointestinal functioning during sleep clearly establishes a new horizon of investigation in both sleep medicine and gastroenterology. 2001 Harcourt Publishers Ltd     

Decreased sympathetic inhibition in gastroesophageal reflux disease

This study was undertaken to evaluate autonomic nervous system function in patients with gastroesophageal reflux disease. Based on clinical criteria, 28 consecutive patients with no history of heart, metabolic, or neurologic disease (mean age 41 y, range 20–62 y) reporting with upper gastrointestinal symptoms typical of gastroesophageal reflux underwent esophageal manometry, ambulatory 24-hour pH study with electrocardiographic monitoring, power spectral analysis of heart rate variability, and cardiovascular tests. Twelve healthy subjects served as controls. A positive result of prolonged esophageal pH study (pH in the distal esophagus less than 4, lasting more than 4.2% of recording time) was observed in 21 patients (reflux group); seven patients were categorized in the nonreflux group. No patient showed arrhythmias or any correlation between heart rate variability changes during electrocardiographic monitoring and episodes of reflux (pH less than 4, lasting more than 5 minutes). A decrease of sympathetic function occurred only in the reflux group (p<0.05) supported by the lower increase of systolic/diastolic blood pressure at sustained handgrip. No other cardiovascular tests showed statistically significant differences in the control or nonreflux groups. Total time reflux showed an inverse correlation with sympathetic function in the reflux group (r=-0.415, p<0.028). We concluded that there is some evidence for a slightly decreased sympathetic function in patients with gastroesophaged reflux disease that is inversely correlated with total time reflux. In these patients, decreased sympathetic function may cause dysfunction of intrinsic inhibitory control with increased transient spontaneous lower-esophageal sphincter relaxations, thus resulting in gastroesophageal reflux disease.     

Increased TRPV1 gene expression in esophageal mucosa of patients with non‐erosive and erosive reflux disease

Background Transient receptor potential channel vanilloid subfamily member‐1 (TRPV1) may play a role in esophageal perception. TRPV1 mRNA and protein expression were examined in the esophageal mucosa of non‐erosive reflux disease (NERD) and erosive esophagitis (EE) patients and correlated to esophageal acid exposure. Methods Seventeen NERD patients, eight EE patients and 10 healthy subjects underwent endoscopy after a 3‐week washout from proton pump inhibitors or H2 antagonists. Biopsies, obtained from the distal esophagus, were used for conventional histology, for Western blot analysis and/or quantitative real‐time polymerase chain reaction (qPCR). Overall 13 NERD patients, four EE patients and five controls underwent ambulatory pH‐testing. Key Results TRPV1 expression was increased in all NERD and EE patients, as measured by Western blot analysis (0.65 ± 0.07 and 0.8 ± 0.05 VS 0.34 ± 0.04 in controls; P < 0.01) and by qPCR (1.98 ± 0.21 and 2.52 ± 0.46 VS 1.00 ± 0.06; P < 0.01). Neutrophilic infiltration, in the mucosa, was detected only in EE patients. Conclusions & Inferences Non‐erosive reflux disease and EE patients presented increased TRPV1 receptors mRNA and protein, although no correlation with acid exposure was demonstrated. Increased TRPV1 in the esophageal mucosa may contribute to symptoms both in NERD and EE patients and possibly account for peripheral mechanisms responsible for esophageal hypersensitivity in NERD patients.     

Impaired egress rather than increased access: an important independent predictor of erosive oesophagitis

Oesophagitis severity is related to total oesophageal acid exposure, which is in turn dependent upon both the number reflux events and the rate of refluxate clearance. This study examined differences in the frequency of reflux events and the characteristics of oesophageal acid exposure in asymptomatic controls and gastro-oesophageal reflux disease (GORD) patients both with and without oesophagitis. Nine controls and 38 patients with GORD were studied. All patients underwent upper endoscopy, videofluoroscopy, determination of resting lower oesophageal sphincter pressure (LOSP) and 24 h pH monitoring. Analysis was performed with subjects grouped as controls, non-erosive GORD and oesophagitis. A second analysis was performed with subjects grouped by hiatal hernia size. Statistical comparisons were made using anovaand unpairedt-tests. Patients with oesophagitis had significantly larger hiatal hernias, greater oesophageal acid exposure, more prolonged episodes of reflux and longer acid clearance times than did controls and patients with non-erosive GORD. No significant difference was seen in the number of reflux events. Increasing hiatal hernia size was significantly associated with increasing oesophageal acid exposure, number of prolonged reflux events and prolonged acid clearance times. Oesophagitis patients have significantly greater oesophageal acid exposure than subjects with non-erosive GORD. Increased oesophageal acid exposure in oesophagitis is attributable to impaired acid clearance and the greatest impairments in refluxate clearance occur in patients with large hiatal hernias.     

Reflux monitoring in children

Recently, multichannel intraluminal impedance (MII) monitoring was added to the repertoire of tests to evaluate the (patho)physiology of gastroesophageal reflux (GER) in children. Its advantage above the sole monitoring of the esophageal pH lies in the ability of the detection of both acid and nonacid GER and to discern between liquid and gas GER. Currently, combined 24 h pH‐MII monitoring is recommended for evaluation of gastro‐esophageal reflux disease (GERD) and its relation to symptoms in infants and children, despite the lack of reference values in these age groups. There is new evidence in the current issue of this Journal supporting the role of pH‐MII monitoring for the evaluation of children presenting with gastrointestinal symptoms suggestive of GERD and the prediction of the presence of reflux esophagitis. However, several issues should be taken into account when performing pH‐MII clinically.     

Efficacy,tolerability and pharmacokinetics of a modified release formulation of ADX10059, a negative allosteric modulator of metabotropic glutamate receptor 5: an esophageal pH‐impedance study in healthy subjects

Background Animal studies show metabotropic glutamate receptor 5 inhibition reduces transient lower esophageal sphincter relaxations and increases lower esophageal sphincter tone. A preliminary, single‐day study, demonstrated oral ADX10059 reduced 24‐h esophageal acid exposure and clinical symptoms in gastro‐esophageal reflux disease (GERD) patients, but had suboptimal tolerability, ascribable to the compound’s rapid absorption. This study evaluated ADX10059 modified‐release (MR) formulation pharmacokinetics, tolerability, and pharmacodynamics. Methods Randomized, double‐blind placebo‐controlled study. Three groups of eight healthy, male subjects received placebo (n = 2) or ADX10059 (n = 6) 50, 125 or 250 mg b.i.d. for 6 days. Esophageal pH‐impedance was performed on day 1 and day 6 of treatment, for 1‐h fasting and for 4 h post refluxogenic meal. Treatment effect was determined by Kruskall–Wallis test and placebo comparison by Wilcoxon rank sum. Key Results Following placebo, reflux episodes increased from day 1 to day 6. Significant treatment effect was seen for total esophageal acid exposure (P = 0.048) and postprandial number of weakly acidic reflux episodes (P = 0.041). Significant differences from placebo were seen for 125 mg b.i.d.; 250 mg b.i.d. was not more effective than 125 mg b.i.d. Twice daily ADX10059 MR gave satisfactory 24‐h exposure and good tolerability. Conclusions & Inferences ADX10059 decreased reflux episodes in healthy subjects. The MR formulation is suitable for longer‐term treatment to evaluate symptom control in GERD patients.     

The effect of baclofen on nocturnal gastroesophageal reflux and measures of sleep quality: a randomized, cross-over trial

Background Baclofen, a GABA_b agonist, has been shown to reduce episodes of gastroesophageal reflux (GER). To determine if baclofen would significantly reduce reflux during sleep, and also improve objective and subjective measures of sleep. Methods Twenty‐one individuals with complaints of nighttime heartburn at least twice a week and a Carlsson GERD score of at least 5 were studied. Patients underwent polysomnography (PSG) and simultaneous esophageal pH monitoring on two occasions separated by approximately 1 week in a cross‐over design. The night of each polysomnographic study, patients consumed a refluxogenic meal. Baclofen (40 mg) or placebo was given in random order 90 min prior to the start of the PSG. Key Results Baclofen significantly reduced the number of reflux events compared with placebo. Upright and recumbent acid contact times were both reduced by baclofen vs placebo, but the differences were not significant. Regarding sleep outcomes, several variables were significantly improved by baclofen. Total sleep time and sleep efficiency increased, and wake after sleep onset decreased in the baclofen condition compared with placebo. Proportion of Stage 1 sleep was also significantly decreased on baclofen. Conclusions & Inferences In addition to reducing the number of reflux events during sleep, baclofen significantly improved several measures of sleep in patients with documented GER and sleep disturbances. Baclofen could therefore be considered as a useful adjunct therapy to proton pump inhibitors (PPIs) in patients with nighttime heartburn and sleep disturbance who continue to have heartburn and/or sleep complaints despite PPI therapy.     

Failure to respond to physiologic challenge characterizes esophageal motility in erosive gastro‐esophageal reflux disease

Background Non‐specific esophageal dysmotility with impaired clearance is often present in patients with gastro‐esophageal reflux disease (GERD), especially those with erosive disease; however the physio‐mechanic basis of esophageal dysfunction is not well defined. Methods Retrospective assessment of patients with erosive reflux disease (ERD; n = 20) and endoscopy negative reflux disease (ENRD; n = 20) with pathologic acid exposure on pH studies (>4.2% time/24 h) and also healthy controls (n = 20) studied by high resolution manometry. Esophageal motility in response to liquid and solid bolus swallows and multiple water swallows (MWS) was analyzed. Peristaltic dysfunction was defined as failed peristalsis, spasm, weak or poorly coordinated esophageal contraction (>3 cm break in 30 mmHg isocontour). Key Results Peristaltic dysfunction was present in 33% of water swallows in controls, 56% ENRD and 76% ERD respectively (P < 0.023 vs controls, P = 0.185 vs ENRD). The proportion of effective peristaltic contractions improved with solid compared to liquid bolus in controls (18%vs 33%, P = 0.082) and ENRD (22%vs 54%, P = 0.046) but not ERD (62%vs 76%, P = 0.438). Similarly, MWS was followed by effective peristalsis in 83% of controls and 70% ENRD but only 30% ERD patients (P < 0.017 vs controls and P < 0.031 vs ENRD). The association between acid exposure and dysmotility was closer for solid than liquid swallows (r = 0.52 vs 0.27). Conclusions & Inferences Peristaltic dysfunction is common in GERD. ERD patients are characterized by a failure to respond to the physiologic challenge of solid bolus and MWS that is likely also to impair clearance following reflux events and increase exposure to gastric refluxate.     

Characteristics of gastro‐esophageal reflux episodes in Barrett’s esophagus,erosive esophagitis and healthy volunteers

Background Gastro‐esophageal reflux is considered a major culprit in the pathogenesis of Barrett’s esophagus (BE). Still, there is controversy on the role of weakly acidic and weakly alkaline reflux in BE. To compare characteristics of reflux episodes patients with BE, erosive esophagitis (EE), and healthy volunteers (HV). Methods One hundred consecutive patients with BE (75 short‐segment BE, 25 long‐segment BE), 50 with EE and 48 HV underwent multichannel intraluminal impedance‐pH off‐therapy. We quantified esophageal acid exposure, characteristics, and proximal extension of reflux episodes. Key Results Total and acid reflux episodes gradually increased from HV [28 (17.5–43) and 18 (8–31)] to EE [73.5 (54–96) and 52 (39–68)], short‐segment BE (SSBE) [83 (73.2–131) and 65 (43.3–95)] and long‐segment BE (LSBE) [105 (102–187) and 77 (75–107)]. Weakly acidic reflux episodes were significantly higher (P < 0.05) in LSBE [36 (27.5–50.5)] and SSBE [34 (18.5–41)] compared to EE [21.5 (15–37)] and HV [19 (14–25)]. No differences in terms of proportion of acid, weakly acidic and weakly alkaline reflux were found [HV (49%–49%–2%) vs EE (68%–32%–1%) vs SSBE (65%–34%–1%) vs LSBE (69%–30%–1%); P = ns]. In LSBE, a higher percentage of reflux episodes (P < 0.05) reached the proximal esophagus (59%) compared with SSBE (43%). Conclusions & Inferences Barrett esophagus patients have more severe reflux as shown by the number of acid and weakly acidic reflux episodes, re‐reflux episodes and proximal migration. Given that PPI change only the pH of the refluxate, the role of weakly acidic reflux in Barrett’s patients on acid suppressive therapy warrants further investigation.     

Motor events underlying gastro-oesophageal reflux in ambulant patients with reflux oesophagitis

Abstract Information on the mechanism of gastro-oesophageal reflux in patients with reflux disease is limited largely to studies in resting recumbent subjects. Evidence exists that both posture and physical activity may influence reflux. The aim of this study was to investigate reflux mechanisms in ambulant patients with reflux oesophagitis. Concurrent ambulatory oesophageal manometry and pH monitoring were performed in 11 ambulant patients with erosive oesophagitis. Lower oesophageal sphincter (LOS) pressure was monitored with a perfused sleeve sensor. Recordings were made for 90 min before and 180 min after a meal. At set times patients sat in a chair or walked. LOS pressure was ≤2 mmHg at the time of reflux for 98% of reflux episodes. Transient LOS relaxation was the most common pattern overall and the predominant pattern in seven patients, whilst persistently absent basal LOS pressure was the most common pattern in four patients. The pattern of LOS pressure was not altered by the presence of hiatus hernia or by walking. Straining occurred at the onset of 31% of acid reflux episodes but often followed the development of an oesophageal common cavity. The occurrence of straining was not influenced by walking. In ambulant patients with reflux oesophagitis: (1) LOS pressure is almost always absent at the time of reflux, usually because of transient LOS relaxation, (2) persistently absent basal LOS pressure is an important mechanism of reflux in a few patients, (3) straining may help to induce acid reflux in a variable proportion of occasions and may in some instances be a response to gas reflux, and (4) walking does not influence the occurrence of reflux or its mechanisms.     

The effects of intraduodenal nutrient infusion on serum CCK,LES pressure,and gastroesophageal reflux

Background Fats cause reflux symptoms in many patients and cholecystokinin (CCK) may play a role. This study was designed to evaluate the effects of intraduodenal nutrient infusion on serum CCK levels, lower esophageal sphincter (LES) pressure, and gastroesophageal reflux (GER). Methods Twenty‐four asymptomatic volunteers were studied. A Dent sleeve catheter assessed LES function while an impedance‐pH catheter measured reflux events. Participants were randomized to fat (F), carbohydrate (C) or protein (P) infusion. Serum CCK and LES pressures were measured at baseline and after nutrient infusion. Key Results Baseline LES pressures and CCK levels were similar in all three groups. A significant linear decrease was found in LES pressure during F, but not C or P, infusion (P = 0.004). A significant interaction effect was noted between the infusion groups and CCK levels (P = 0.002). A significant linear increase was noted in CCK levels during F but not during C or P infusion (P = 0.02). A significant inverse correlation was found between CCK levels and LES pressure (ρ = ?0.43; P = 0.04). Esophageal acid exposure was significantly increased in the F infusion group (median; interquartile range: 1.10%; 0.25–4.7%) compared to both the C (0.03%; 0.00–0.39%) and P infusion (0.03%; 0.00–0.39%) groups (P = 0.04). Conclusions & Inferences Intraduodenal F infusion was associated with an increase in CCK levels, while P and C were not. LES pressure decreased significantly after fat infusion and reflux events were more frequent. Fat‐induced CCK release is another mechanism that contributes to GER.     

Modulation of upper and lower esophageal sphincter tone during sleep

BACKGROUND AND PURPOSE: The pressures generated within the upper esophageal sphincter (P(UES)) and lower esophageal sphincter (P(LES)) reflect the integrity of these barriers to gastroesophageal and pharyngoesophageal reflux, respectively. This study sought to describe the effects of sleep, respiration and posture on the function of the UES and the LES and the pressure differentials developed across them. METHODS: Ten healthy volunteers (7M, 3F: 38+/-10 yr) without a history of sleep-disordered breathing or reflux underwent overnight polysomnography with simultaneous measurement of P(LES) and P(UES) using a purpose-built sleeve device (Dentsleeve). Posture was recorded but not controlled. RESULTS: Subjects slept for 4.3+/-1.6h. Compared to waking values, both end-inspiratory and end-expiratory Pues were significantly less during slow wave sleep (SWS) (p<0.05). However, P(LES) was unaffected by sleep stage. During wakefulness and all stages of sleep, both P(UES) and P(LES) were greater at end-inspiration than end-expiration (p<0.05). Similar relationships were observed whether subjects were supine or in the lateral decubitus position. CONCLUSION: Sleep decreases the effectiveness of the UES to act as a barrier to pharyngoesophageal reflux, particularly during slow wave sleep (SWS). UES pressure varies with respiration, with minimal values observed during expiration. Hence, barrier function of the UES appears most impaired during SWS, in the expiratory phase of the respiratory cycle. The LES pressure and its barrier pressure also vary with respiration, being least during expiration. However, unlike the UES, the function of the LES was unaffected by sleep.     

Effect of Esophageal Acid Exposure on Upper Esophageal Sphincter Pressure

To investigate the relationship between gastroesophageal reflux and upper esophageal sphincter (UES) pressure, total esophageal acid exposure times on 23-hour ambulatory pH monitoring were compared with UES manometric results in 98 subjects, 85 with laryngopharyngeal symptoms and 13 asymptomatic controls. There was no correlation of acid exposure time with tonic UES pressure nor with any UES wet swallow parameter. The response of the UES to acute upper esophageal acid infusion was assessed in another 13 patients by a sleeve catheter. There was no significant increase of tonic sleeve UES pressure during acid infusion. In contrast to most previous reports, our results indicate that esophageal acid exposure, whether acute or chronic, has little influence on the UES.