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.     

Effect of oesophagitis on proximal extent of gastro-oesophageal reflux

Proximal oesophageal acid reflux is increased in gastro-oesophageal reflux disease (GORD) patients with oesophageal and extra-oesophageal symptoms, the latter particularly in presence of oesophagitis. This study was aimed to assess the proximal extent of reflux, both acid and weakly acidic, in GORD patients with and without oesophagitis and to characterize, using an animal model of GORD, the relationship between acute oesophagitis and proximal extent of reflux. Proximal extent of reflux was evaluated during 24-h pH-impedance monitoring in 17 oesophagitis, 27 non-erosive reflux disease (NERD) patients and 10 asymptomatic controls. In five adult cats, reflux events were simulated by intra-oesophageal retrograde injection of a radiopaque solution. Proximal extent of simulated reflux was fluoroscopically assessed before and after inducing acute oesophagitis. The percentage of proximal reflux was 11% in controls, 22% in NERD and 38% in oesophagitis patients (P < 0.05 vs NERD). Weakly acidic reflux showed higher proximal extent in oesophagitis than in NERD patients but it was less proximally propagated than acid reflux. In cats, proximal reflux was significantly increased during acute oesophagitis. Oesophagitis patients show higher proximal extent of reflux, acid and weakly acidic, when compared with NERD patients and controls. In the experimental model, acute oesophagitis favours proximal migration of simulated reflux.     

Regional oesophageal sensitivity to acid and weakly acidic reflux in patients with non-erosive reflux disease

Abstract  The mechanisms underlying symptoms in non-erosive reflux disease (NERD) remain to be elucidated. Non-erosive reflux disease patients appear to be more sensitive to intraluminal stimula than erosive patients, the proximal oesophagus being the most sensitive. In order to assess regional oesophageal changes in reflux acidity and sensitivity to reflux, according either to the acidity or the composition of the refluxate, combined multiple pH and multiple pH-impedance (pH-MII) was performed in 16 NERD patients. According to multiple pH-metry, 29% and 12% of reflux events reached the middle and proximal oesophagus respectively, and 35% and 19% according to conventional pH-MII ( P  < 0.05). The per-individual analysis confirmed the difference between the two techniques. According to combined distal and proximal pH-MII, approximately 30% of distal acid reflux became weakly acidic at the proximal oesophagus. In all patients, the frequency of symptomatic refluxes, both acid and weakly acidic, was significantly higher at the proximal, compared with distal oesophagus (25 ± 8% vs 11 ± 2% for acid reflux and 27 ± 8% vs 8 ± 2% for weakly acidic reflux; P  < 0.05). Compared with multiple pH-metry, pH-MII shows a higher sensitivity in the detection of proximal reflux. As approximately 30% of acid reflux becomes weakly acidic along the oesophageal body, to better characterize proximal reflux, in clinical practice, combined proximal pH-impedance monitoring should be used. In NERD patients, the proximal oesophagus seems to be more sensitive to both acid and weakly acidic reflux.     

Ambulatory oesophageal pressure,pH and ECG recording in patients with normal and pathological coronary angiography and intermittent chest pain

Abstract The present study was performed to compare pain-related oesophageal motility, gastro-oesophageal reflux and ST-segment deviations in patients with intermittent chest pain and normal or pathological coronary angiography. Thirty patients (11 males, 19 females; mean age 54.8 years) with normal and 15 patients (12 males, 3 females; mean age 66.7 years) with pathological coronary angiography were investigated by 24-h oesophageal pressure, pH and ECG recording. Chest pain correlated with motility abnormalities or gastro-oesophageal reflux occurred in 33% (10/30) of patients with normal coronary arteries and in 26% of patients with pathological coronary angiography. Symptomatic and asymptomatic ST-segment changes were less frequently observed in patients with normal angiography (4/30) than in patients with pathological coronary angiography (7/14; P = 0.02). Oesophageal dysfunction coincided with ST-segment deviation in 6.7% (2/30) of patients with normal and 40% (6/15) of patients with pathological coronary angiography (P = 0.02). The conclusions reached were: (1) pain-correlated abnormal motility or gastro-oesophageal reflux occurred in patients with normal and pathological coronary angiography at the same frequency; (2) ambulatory motility and pH recording alone does not appear to differentiate between cardiac and non-cardiac chest pain; (3) simultaneous ECG recording reveals a significant correlation of ST-segment deviation and gastro-oesophageal reflux or abnormal motility in patients with coronary artery stenosis.     

Mechanisms of gastro-oesophageal reflux in the lateral decubitus positions

Gastro-oesophageal reflux is more common in the right than in the left lateral position but the reasons why are not well understood. We have therefore studied the mechanisms underlying reflux in the lateral decubitus positions in patients with reflux disease. Fifteen patients with symptomatic reflux and excessive oesophageal acid exposure were studied (nine male, age 25-63 years). Each was intubated with a perfused manometric assembly, incorporating a Dent sleeve, and a pH probe. Following a 30-min basal period, a 400-kCal meal was infused into the stomach and patients were studied for 60 min in each lateral position. Following infusion of the meal, lower oesophageal sphincter (LOS) pressure fell and transient LOS relaxation (TLOSR) frequency increased. Acid reflux episodes were more common in the postprandial period (fasting 0 (0-6) h, first postprandial hour 1 (0-9) h, P = 0.0002, second postprandial hour 1 (0-22) h, P = 0.02) and occurred more than twice as often in the right lateral position (right 3 (0-22) h, left 0 (0-10) h, P = 0.01). However, TLOSRs, swallow-related relaxations and low basal LOS pressures were equally common in both lateral positions. In patients with reflux disease, postprandial reflux is twice as common in the right lateral position. This does not relate to differences in gastro-oesophageal junctional pressure, suggesting that other aspects of barrier function or differences in the intragastric distribution of chyme may be important.     

Reproducibility of meal-induced transient lower oesophageal sphincter relaxations in patients with gastro-oesophageal reflux disease

AIM: To calculate the number of subjects required in trials investigating drugs reducing the number of transient lower oesophageal sphincter relaxations (TLOSRs), the inter- and intra-individual variability of TLOSRs were determined, using meal ingestion as a trigger of TLOSRs and reflux. METHODS: A total of 23 gastro-oesophageal reflux disease (GORD) patients with no to grade B oesophagitis and a hiatal hernia < or =3 cm underwent oesophageal manometry and pHmetry 1 h before and 3 h after ingestion of a solid meal on two separate days approximately 4 weeks apart. Reflux episodes and the underlying mechanisms and the number of TLOSRs were evaluated. RESULTS: The number of TLOSRs, reflux episodes and % time with pH < 4 after meal ingestion did not differ significantly between the two sessions. The intra-individual variation of TLOSRs in the 3 h postprandial period (24.4) was smaller compared with the inter-individual variation (47.5). Transient lower oesophageal sphincter relaxations were the predominant cause of reflux accounting for 61 +/- 7 and 70 +/- 5% of the reflux episodes in visits 1 and 2, respectively. CONCLUSIONS: These data for the first time provide information on the variability of TLOSRs and reflux evoked by meal ingestion, which is of crucial importance for the design and power calculations of future clinical studies evaluating the efficacy of new drugs targeting TLOSRs.     

Postprandial gastric antral contractions in patients with gastro-oesophageal reflux disease: a scintigraphic study

Abstract  Disturbed gastric contractility has been found in manometric studies in patients with gastro-oesophageal reflux disease (GORD), but the pathophysiological role of this abnormality is unclear. We aimed at assessing postprandial gastric antral contractions and its relationships with gastric emptying and gastro-oesophageal reflux in GORD patients. Fasted GORD patients ( n  = 13) and healthy volunteers ( n  = 13) ingested a liquid meal labelled with 72 MBq of ^99mTechnetium-phytate. Gastric images were acquired every 10 min for 2 h, for measuring gastric emptying half time. Dynamic antral scintigraphy (one frame per second), performed for 4 min at 30-min intervals, allowed estimation of both mean dominant frequency and amplitude of antral contractions. In GORD patients ( n  = 10), acidic reflux episodes occurring 2 h after the ingestion of the same test meal were determined by ambulatory 24-h oesophageal pH monitoring. Gastric emptying was similar in GORD patients and controls (median; range: 82 min; 58–126 vs 80 min; 44–122 min; P  = 0.38). Frequency of antral contractions was also similar in both groups (3.1 cpm; 2.8–3.6 vs 3.2 cpm; 2.4–3.8 cpm; P  = 0.15). In GORD patients, amplitude of antral contractions was significantly higher than in controls (32.7%; 17–44% vs 23.3%; 16–43%; P  = 0.01), and correlated positively with gastric emptying time ( R _s = 0.58; P  = 0.03) and inversely with the number of reflux episodes ( R _s = −0.68; P  = 0.02). Increased amplitude of postprandial gastric antral contractions in GORD may comprise a compensatory mechanism against delayed gastric emptying and a defensive factor against acidic gastro-oesophageal reflux.     

Relationships between air swallowing, intragastric air, belching and gastro-oesophageal reflux

BACKGROUND: With each swallow a certain amount of air is transported to the stomach. The stomach protects itself against excessive distention by swallowed air through belching (gas reflux). The mechanism of belching (transient lower oesophageal sphincter relaxation) is also one of the mechanisms underlying gastro-oesophageal reflux. AIM: To investigate whether swallowing of air leads to an increase in size of the intragastric air bubble and to gastro-oesophageal reflux. METHODS: Multichannel intraluminal impedance measurement was used to quantify the incidence of swallowing of air in 20 healthy volunteers before and after a meal. Radiography was used to measure the size of the intragastric air bubble. Gastro-oesophageal reflux was assessed by concurrent impedance and pH measurement. RESULTS: The rate of air swallowing was correlated to the size of the intragastric air bubble postprandially and to the rate of gaseous gastro-oesophageal reflux. The number of air swallows and the size of the intragastric air bubble did not correlate with the number of liquid acid and non-acid reflux episodes. CONCLUSIONS: In healthy subjects, air swallowing promotes belching but does not facilitate acid reflux.     

Regional gastric emptying abnormalities in functional dyspepsia and gastro-oesophageal reflux disease

To characterize proximal and distal stomach emptying in functional dyspepsia (FD) and gastro-oesophageal reflux disease (GORD). Eighty-three patients underwent gastric emptying (GE) scintigraphy and symptom scoring for the evaluation of upper gastrointestinal symptoms and were divided into three groups: FD (n = 25), GORD (n = 20) and FD + GORD (n = 38). Total, proximal and distal gastric retention were determined scintigraphically and compared with normal controls. Delayed total GE was observed in each subgroup: FD (56%), GORD (45%) and FD + GORD (55%). Greater proximal gastric retention was observed after meal ingestion in GORD compared to FD. Greater distal gastric retention was observed in FD and FD + GORD but it was only mild in GORD. Nausea, vomiting, early satiety, distention and regurgitation were associated with proximal gastric retention whereas there was no symptom associated with distal gastric retention. Multiple regression demonstrated total gastric retention at 30 min and 1 h was positively correlated with regurgitation whereas early proximal gastric retention was positively correlated with regurgitation and negatively correlated with nausea. Selective abnormalities of proximal and distal stomach emptying were demonstrated in GORD and FD. GORD and FD symptoms were associated with proximal gastric retention suggesting that proximal stomach motor function may be important in the pathogenesis of symptoms associated with these disorders.     

Heartburn during sleep: a clinical marker of gastro-oesophageal reflux disease in morbidly obese patients

Abstract Gastro‐oesophageal reflux disease (GORD) and morbid obesity are entities with increasing prevalence. New clinical strategies are cornerstones for their management. The aim of this study was to assess the prevalence of heartburn during sleep (HDS) and whether this symptom predicts the presence of objective GORD parameters and increased heartburn perception in morbidly obese patients. Ninety‐one consecutive morbidly obese patients underwent clinical evaluation, upper gastrointestinal endoscopy and oesophageal pH monitoring. HDS was characterized when patients replied positively to the question, ‘Does heartburn wake you from sleep?’. A General Score for Heartburn (GSH) ranging between 0 and 5 was assessed with the question ‘How bad is your heartburn?’. HDS was reported by 33 patients (36%). More patients with HDS had abnormal acid contact time or reflux oesophagitis than patients without HDS (94%vs 57%, P < 0.001). HDS had a positive predictive value of 94% (0.95 CI 82–98), sensitivity of 48% (0.95 CI 37–60%) and specificity of 93% (0.95 CI 77–98%) for detection of GORD. A higher proportion of patients with HDS perceived heartburn preceded by acid reflux in diurnal (39%vs 9%; P < 0.001) periods during pH‐metry. HDS patients showed higher GSH (2.4 ± 0.5 vs 1.7 ± 0.4; P < 0.0001) compared with patients who denied HDS but reported diurnal heartburn. HDS occurs in a significant minority of patients with morbid obesity and has high positive predictive value for GORD. Symptomatic reflux during the sleep seems to be a marker of increased heartburn perception in this population.     

Gastro-oesophageal reflux of liquids and gas during transient lower oesophageal sphincter relaxations

Some transient lower oesophageal sphincter relaxations (TLOSRs) are accompanied by gastro-oesophageal reflux and others are not. We aimed to investigate what factors determine the occurrence and type of reflux during TLOSRs. In 12 healthy subjects prolonged high-resolution manometry was performed. Reflux was detected using pH-impedance monitoring. A total of 219 TLOSRs were detected; no differences were observed between the duration of TLOSRs with liquid-containing reflux (20.2 +/- 1.0 s), gas reflux (17.0 +/- 1.0 s) and no reflux (19.0 +/- 1.0 s). Trans-sphincteric pressure gradient was similar in TLOSRs with liquid reflux (1.6 +/- 0.1 kPa), gas reflux (1.5 +/- 0.1 kPa) and no reflux (1.7 +/- 0.3 kPa). Prevalence, duration and amplitude of oesophageal pre-contractions and sphincteric after-contractions were not different for TLOSRs with and without reflux. The total number of TLOSRs decreased significantly from 8.2 +/- 0.8 in the first to 5.7 +/- 0.5 in the second and 4.4 +/- 0.6 in the third 70-min recording period. The number of TLOSRs accompanied by liquid-containing reflux decreased from 4.7 +/- 0.9 to 3.0 +/- 0.4 to 1.6 +/- 0.4, while the numbers of TLOSRs with gas reflux remained unchanged (2.1 +/- 0.6-2.1 +/- 0.7-2.2 +/- 0.6). Besides, time after the meal, no differences were observed in the characteristics of TLOSRs with and without gastro-oesophageal reflux. We conclude that factors, other than TLOSR characteristics, are important of whether or not a TLOSR is reflux-related.     

Transient lower oesophageal sphincter relaxations play an insignificant role in gastro-oesophageal reflux to the proximal oesophagus.

Gastro-oesophageal reflux to the proximal oesophagus may cause atypical symptoms of gastro-oesophageal reflux disease (GORD). The motor abnormalities underlying reflux into the proximal oesophagus are still unclear. The aim of this study was to analyse the oesophageal motility during reflux into the proximal oesophagus in a group of healthy subjects and in patients with atypical symptoms of GORD. We concentrated particularly on lower oesophageal sphincter (LOS) activity and transient lower oesophageal sphincter relaxations (TLOSRs). Ten patients (7M, 3F, age 25-51 years) with mild oesophagitis (Savary-Miller grade I-II) and 10 healthy subjects (6M, 4F, age 23-54 years) underwent a 24-h dual pH-metric and manometric recording, using an electronic portable device. This recorded distal and proximal oesophageal pH values, oesophageal body and LOS motility. GORD patients had more distal and proximal reflux (DR and PR) compared with healthy controls (DR P < 0.001; PR P < 0.05). TLOSRs were the most frequent event during reflux into the distal oesophagus, whereas TLOSR frequency was much lower during reflux to the proximal oesophagus in GORD patients and in healthy controls (P < 0.05 and P < 0.01 vs. distal reflux, respectively). A significant relationship between TLOSRs and distal refluxes was present but no relationship with proximal reflux was detected. We conclude that TLOSRs are much less frequent during reflux to the proximal oesophagus than distal oesophageal reflux in patients with mild GORD suffering from atypical manifestations. The mechanism of acid reflux to the proximal oesophagus is unclear.     

Characterization of intraluminal impedance patterns associated with gas reflux in healthy volunteers

Abstract  Multichannel intraluminal impedance (MII) recording allows assessment of flow through the oesophagus and differentiation between liquid and gas contents. Existing MII criteria for recognition of gas gastro-oesophageal reflux (GOR) have not been validated during known gas GOR in humans. Aims: (i) Characterize MII patterns of known gas GOR and optimize criteria. (ii) Clarify interrelationships between magnitude of maximal impedance change, luminal diameter and electrode-mucosa contact. Ten healthy volunteers (six male, 21–37 years) were studied using an oesophageal MII-manometry catheter. After catheter placement, subjects were asked to drink 600 mL of carbonated soft drink. Recordings were made for 20 min and the protocol repeated. Reported belches confirmed manometrically (triggered by transient lower oesophageal sphincter relaxations) were included for analysis. Those episodes were compared against commonly used criteria. Another five subjects (three male, 26–52 years) underwent simultaneous MII and videofluoroscopy using the same protocol. Videofluoroscopic images were analyzed for luminal diameter and the presence of electrode–mucosa contact. All analyzed gas GOR episodes ( n  = 88) were associated with a pattern of impedance rise which was either retrograde (62.5%), synchronous (19.3%) or antegrade (18.2%). Depending on the exact criteria used, sensitivity ranged from 33% to 75%. A multivariate regression model including luminal diameter and the presence of electrode-mucosa contact as independent factors accounted for 53% of all variation in impedance changes. In conclusion, a significant number of gas GOR episodes does not meet criteria for their recognition. New criteria are proposed to include specific antegrade patterns of impedance rise. Luminal diameter and the extent of contact between the oesophageal mucosa and MII-electrodes influence the magnitude and patterning of impedance change.     

Relationship between gastro-oesophageal reflux pattern and severity of mucosal damage

Abstract  The aim of the study is to compare the characteristics of reflux episodes in controls and in patients with various degrees of oesophagitis and Barrett's oesophagus. Ambulatory 24-h impedance-pH tracings were analysed from healthy volunteers, patients with non-erosive reflux disease (NERD), patients with grade A oesophagitis, grade B oesophagitis, grade C or D oesophagitis and patients with a short segment (<2 cm) of Barrett's metaplasia. The number of acid and weakly acidic reflux episodes increased from 25.9 ± 3.9 to 17.9 ± 1.5 in the controls, 39.9 ± 6.3 to 33.4 ± 5.7 in the patients with NERD, 46.6 ± 6.2 to 40.4 ± 9.2 in grade A, 68.2 ± 9.2 to 49.2 ± 12.3 in grade B, 79.8 ± 15.6 to 47.4 ± 4.6 in grade C/D and 75.1 ± 7.9 to 37.3 ± 8.5 in the patients with Barrett. The proportion of reflux episodes that is acidic or alkaline was similar all groups. Comparison with normal values revealed that none of the controls, 40% of the patients with NERD, 50% of the patients with grade A, 80% of the patients with grade B and all patients with grade C/D or Barrett's oesophagus had an abnormally high total number of reflux episodes. In the patients with severe oesophagitis a significantly higher percentage of reflux episodes reached the proximal oesophagus (43.8%) compared to the patients with Barrett's oesophagus (19.2%). With increasing degrees of oesophagitis, patients have more reflux episodes but a large overlap between the groups exists making comparison with normal values of limited relevance. In patients with Barrett's oesophagus fewer reflux episodes reach the proximal oesophagus which might explain their low sensitivity to reflux.     

Proximal oesophagus: the added value in understanding GORD symptoms

Abstract  Over the past decade, the approach to the understanding of the mechanisms involved in the aetiology of gastro-oesophageal reflux disease (GORD) symptoms has changed, and growing evidence now supports the concept that visceral hyper-sensitivity to intra-oesophageal stimuli plays a major role. Among the recent advances, one of the more consistent findings is that the contact of the refluxate, either acidic or weakly acidic, with the proximal oesophageal mucosa, is a main determinant of GORD symptoms, particularly in the large majority of patients affected by non-erosive reflux disease. The data reported in the current issue of Neurogastroenterology and Motility by Bredenoord et al ., showing only a small proportion of proximal reflux in patients with Barrett's oesophagus, who are less sensitive to gastro-oesophageal reflux, further support the consistency of this finding in the pathogenesis of symptoms. In the light of these results, we shall look forward, in the management of patients, to approaches aimed at restoring the antireflux barrier, hopefully decreasing the amount of reflux and, in turn, its proximal extent.