Does acute psychological stress increase perception of oesophageal acid?

Abstract Gastro‐oesophageal reflux disease (GORD) patients often report an increase in their reflux symptoms during stressful situations. The aim of this study was to assess the influence of acute psychological stress on oesophageal acid perception. In 15 healthy volunteers and 10 GORD patients with a positive symptom–reflux association an oesophageal acid perfusion test was performed, once with and once without the presence of an acute psychological stressor (IQ test). The order of the measurements was randomized. The time from onset of the acid infusion to first acid perception, discomfort and pain was noted. Blood pressure was measured to assess the effect of the stress task. In healthy volunteers, the time to first perception (control task: 617 ± 174 s vs stress task: 561 ± 162 s), discomfort (control task: 969 ± 158 s vs stress task: 940 ± 151 s) or pain (control task: 1393 ± 122 s vs stress task: 1366 ± 121 s) did not differ significantly between both measurements. In GORD patients, no significant differences between both measurements were found either in time to first perception (control task: 63 ± 26 s vs stress task: 43 ± 15 s), discomfort (control task: 153 ± 44 s vs stress task: 249 ± 62 s) or pain (control task: 558 ± 139 s vs stress task: 633 ± 118 s). Systolic blood pressure rose significantly during the stress task in both the healthy volunteers (6 ± 1 mmHg) and the GORD patients (9 ± 2 mmHg). Neither in the healthy volunteers nor in the GORD patients, the acute psychological stress induced by an IQ test increased oesophageal acid perception. The observed increase in systolic blood pressure shows that the experimental stressors were effective.     

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.     

Patients with physiological acid exposure and positive symptom association scores: a distinct group within the GORD spectrum

Abstract  Studies comparing pH-metrically well-characterized gastro-oesophageal reflux disease (GORD) patients with physiological reflux to GORD patients with pathological reflux, with regard to clinical and epidemiological data, are lacking. We included 273 GORD patients with pathological 24-h pH-monitoring (pH+), defined as pH<4 ≥ 6% of time. A symptom index (SI) ≥ 50% was considered positive, as well as a symptom association probability (SAP) ≥ 95%. We included 84 GORD patients with physiological acid exposure (pH−) and a positive SI and/or SAP. Manometry and endoscopy reports were reviewed. Subjects completed questionnaires about demographics and medical history, functional dyspepsia and irritable bowel syndrome, the Nepean Dyspepsia Index symptom score and the RAND-36 quality of life scale. pH− patients were younger (45 vs 50 years, P  = 0.003), more often female (60% vs 39%, P  = 0.001), smoked more (31% vs 19%, P  = 0.021) and reported proton pump inhibition failure more often (47% vs 32%, P  = 0.027). A hypotensive lower oesophageal sphincter was less common in pH− patients (18% vs 34%, P  = 0.008) and distal oesophageal contraction amplitude was higher (11 vs 9.5 kPa, P  = 0.045). pH− patients had hiatal hernia and oesophagitis less often (48% vs 73%, P  < 0.0005; 36% vs 54%, P  = 0.012 respectively). pH− patients less often reported no other symptoms besides GORD (20% vs 34%, P  = 0.015). pH− patients scored worse at the Nepean (reflux 19 vs 12 out of 39, P  < 0.0005; dyspepsia 54 vs 38 out of 156, P  < 0.0005). In the subgroup of patients who have physiological oesophageal acid exposure the enhancement of the perceived symptom burden appears to be the most important mechanism in GORD pathogenesis.     

Increased swallowing frequency in GORD is likely to be caused by perception of reflux episodes

Abstract  Patients with gastro-oesophageal reflux disease (GORD) swallow air more frequently and have more gas-containing reflux episodes than healthy controls. One explanation for this phenomenon may be that GORD patients primarily swallow more frequently and, as a consequence, have more swallow- or transient lower oesophageal sphincter relaxation-associated reflux episodes. Another explanation may be that GORD patients swallow more often in response to perception of reflux episodes. The aim of this study was to differentiate between these two possible mechanisms. In 34 patients with typical reflux symptoms oesophageal 24-h pH-impedance monitoring was performed twice, once off and once on proton pump inhibitor (PPI) therapy. The number of reflux episodes and number of swallows and air swallows was evaluated. The symptom association probability (SAP) was used to distinguish patients with a good relationship between symptoms and reflux episodes (SAP+) from those who had not (SAP−). In both the SAP+ ( n  = 21) as SAP− patients ( n  = 13), the acid exposure time decreased during PPI therapy. In the SAP+ patients, the number of swallows decreased on PPI (829 ± 85 off vs 701 ± 79 on PPI, P  < 0.05), whereas in the SAP− patients, the incidence of swallows (802 ± 93 off vs 814 ± 69 on PPI, P  = NS) was not influenced by the PPI therapy. PPI therapy reduces the number of swallows in patients with a positive SAP, but not in those with a negative SAP. This finding supports the hypothesis that the increased incidence of swallows in GORD is brought about by responses to perceived reflux events.     

The gastro-oesophageal common cavity revisited

The manometric common cavity phenomenon has been used as indicator of gastro-oesophageal reflux of liquid or gaseous substances. Using combined pH and impedance recording as reference standard the value of a common cavity as indicator of gastro-oesophageal reflux was tested. Ten healthy male subjects underwent combined stationary pressure, pH and impedance recording for 4.5 h. After 1.15 h of recording, a reflux-eliciting meal was consumed. The chi-squared and Kolmogorov-Smirnov tests were used for the statistical analysis. A common cavity was found in 95 (43%) of the 223 reflux events detected by impedance, while seven common cavities were unrelated to a reflux episode. In 54% of the reflux events detected by impedance without a common cavity, a possible common cavity was obscured by either contractile activity or artefacts of various origin. The types of reflux associated with a common cavity (liquid 60%, mixed 31%, gas 9%) and without a common cavity (liquid 59%, mixed 29%, gas 12%) did not differ, or did the acidity of the reflux episodes (with common cavity: acid 67%; without common cavity: acid 58%). The common cavity is a specific but not a sensitive marker of gastro-oesophageal reflux. Furthermore, common cavities are not specific for a particular type of reflux.     

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.     

Relationship between the mechanism of gastro-oesophageal reflux and oesophageal acid exposure in patients with reflux disease

Abstract  This study investigated the relationship between the oesophageal acid exposure time and the underlying manometric motor events in patients with gastro-oesophageal reflux disease (GORD). In 31 patients, 3-hour oesophageal motility and pH were measured after a test meal. Ten patients underwent 24-hour ambulatory manometry and pH recording. In the 3-hour postprandial study, of 367 reflux episodes 79% was associated with a transient lower oesophageal sphincter relaxation (TLOSR), 14% with absent basal lower oesophageal sphincter (LOS) pressure and the remaining 7% with other mechanisms, representing 62, 28 and 10% of the acid exposure time, respectively. Acid reflux duration per motor mechanism was longer for absent basal LOS pressure than for TLOSR (189 ± 23 s and 41 ± 5 s, respectively, P  < 0.001). In the 24-hour ambulatory study, the contribution of TLOSRs to reflux frequency vs acid exposure time were 65 vs 54% interprandially and 74 vs 53% after the meal. During the night, absence of basal LOS pressure accounted for 36% of reflux events representing 71% of acid exposure time. In conclusion, the duration of oesophageal acid exposure following a TLOSR is shorter than reflux during absent basal LOS pressure. TLOSRs are, the major contributor to oesophageal acid exposure during the day. At night, however, reflux during absent basal LOS pressure is the major contributor to acid exposure.     

Assessment of oesophageal motor function using combined perfusion manometry and multi-channel intra-luminal impedance measurement in normal subjects

Multichannel intraluminal impedance (MII) is being used increasingly to assess oesophageal bolus clearance. However, there is no good standardization of the impedance parameters that define 'effective bolus clearance'. The aim of this study was to define these important impedance parameters and to determine their normal values. Concurrent perfusion manometry and MII were performed in 42 healthy volunteers. Ten, 5-mL liquid (saline) boluses and then, 10x5-mL low impedance viscous boluses were tested in each subject in the right-lateral position. Normal values for bolus presence time (BPT) at each site and total bolus transit time (TBTT) were determined from either 'normal' peristaltic responses (amplitude>or=30 mmHg in distal oesophagus) or 'super-normal' peristaltic responses (amplitudes>or=50 mmHg at all sites). The relationship between BPT and TBTT within a response and per-individual performance was determined. A total of 840 swallows of liquids and viscous responses were analysed. BPT and TBTT of viscous swallows were longer than those for liquids. Non-peristaltic responses were significantly more likely not to clear a viscous than a liquid bolus. Within a response, the number of sites with prolonged BPT strongly predicted the incidence of prolonged TBTT. Using impedance criteria, normal oesophageal bolus clearance is defined when an individual completely clears at least 70% of liquid responses and at least 60% of viscous responses. This study provides normal values for impedance measurement of bolus clearance when combined with perfusion manometry. These values will allow standardization of impedance application in oesophageal function testing, in both research and clinical setting.     

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.     

Impact of nadir lower oesophageal sphincter pressure on bolus clearance assessed by combined manometry and multi-channel intra-luminal impedance measurement

Abstract  This study aimed to assess the relationship between nadir lower oesophageal sphincter pressure (LOSP) and wave amplitude (WA) in oesophageal bolus clearance. Concurrent oesophageal manometry and impedance were performed in 146 subjects [41 healthy, 24 non-obstructive dysphagia (NOD) and 81 gastro-oesophageal reflux (GOR)]. Patients with achalasia and diffuse oesophageal spasm were excluded. Swallow responses were categorized by nadir LOSP. For each category of nadir LOSP, WA at the distal 2 recording sites were grouped into bins of 10 mmHg and the proportion of waves in each bin associated with a normal bolus presence time (BPT) was determined. Nadir LOSP, distal BPT, total bolus transit time and the proportion of impaired oesophageal clearance in patients with NOD were greater than those of healthy subjects and patients with GOR. Overall, responses with impaired oesophageal clearance had significantly lower WA (54 ± 1 vs 81 ± 1 mmHg; P  < 0.0001) and higher nadir LOSP (2.7 ± 0.4 vs 1.0 ± 0.1 mmHg, P  < 0.001). For each level of nadir LOSP, there was a direct relationship between distal WA and successful bolus clearance of both liquid and viscous boluses from the distal oesophagus. As nadir LOSP increased, the relationship between WA and bolus clearance shifted to the right and higher amplitudes were required to achieve the same effectiveness of clearance. Hypotensive responses with nadir LOSP ≥3 mmHg were less likely to clear than those with nadir LOSP <3 mmHg, for both liquid (7/29 vs 162/276; P  < 0.001) or viscous boluses (11/46 vs 176/279; P  <   0.0001). Nadir LOSP is an important determinant of bolus clearance from the distal oesophagus, particularly in patients with NOD.