Summary
Background
The pathogenesis of gastro‐oesophageal reflux disease (GERD) is complex and multifactorial. The oesophageal hypervigilance and anxiety scale (EHAS) is a novel cognitive‐affective ...evaluation of visceral sensitivity.
Aims
To investigate the interrelationship between EHAS and reflux symptom severity, psychological stress, acid reflux burden, phenotypes, and oesophageal mucosal integrity in patients with GERD.
Methods
Patients with chronic reflux symptoms and negative endoscopy underwent 24‐hour impedance‐pH monitoring for phenotyping, acid reflux burden, and mucosal integrity with mean nocturnal baseline impedance (MNBI) calculation. Validated scores for patient‐reported outcomes, including EHAS, GERD questionnaire (GERDQ), State‐Trait Anxiety Inventory score, and Taiwanese Depression Questionnaire score, were recorded.
Results
We enrolled 105 patients, aged 21‐64 years (mean, 48.8), of whom 58.1% were female; 27 had non‐erosive reflux disease, 43 had reflux hypersensitivity and 35 had functional heartburn. There were no significant differences in sex, EHAS, GERDQ, questionnaires of depression or anxiety among GERD phenotypes. EHAS was significantly correlated with GERDQ, questionnaires of depression and anxiety (P < 0.05). However, there were no significant correlations between GERDQ and questionnaires of depression or anxiety. Regarding patient‐reported outcomes, GERDQ positively correlated with acid exposure time and negatively correlated with MNBI (P < 0.05).
Conclusions
EHAS associates with reflux symptom severity and psychological stress but not with acid reflux burden or mucosal integrity. Thus, EHAS assessment shows promise in assessment of subjective patient outcome and satisfaction with treatment, a hitherto unmet clinical need.
The putative modulators for reflux symptom severity.
Background/Aim
Reflux episodes and postreflux swallow‐induced peristaltic wave (PSPW) index are useful impedance parameters that can augment the diagnosis of gastroesophageal reflux disease (GERD). ...However, manual analysis of pH‐impedance tracings is time consuming, resulting in limited use of these novel impedance metrics. This study aims to evaluate whether a supervised learning artificial intelligence (AI) model is useful to identify reflux episodes and PSPW index.
Methods
Consecutive patients underwent 24‐h impedance‐pH monitoring were enrolled for analysis. Multiple AI and machine learning with a deep residual net model for image recognition were explored based on manual interpretation of reflux episodes and PSPW according to criteria from the Wingate Consensus. Intraclass correlation coefficients (ICCs) were used to measure the strength of inter‐rater agreement of data between manual and AI interpretations.
Results
We analyzed 106 eligible patients with 7939 impedance events, of whom 38 patients with pathological acid exposure time (AET) and 68 patients with physiological AET. On the manual interpretation, patients with pathological AET had more reflux episodes and lower PSPW index than those with physiological AET. Overall accuracy of AI identification for reflux episodes and PSPW achieved 87% and 82%, respectively. Inter‐rater agreements between AI and manual interpretations achieved excellent for individual numbers of reflux episodes and PSPW index (ICC = 0.965 and ICC = 0.921).
Conclusions
AI has the potential to accurately and efficiently measure impedance metrics including reflux episodes and PSPW index. AI can be a reliable adjunct for measuring novel impedance metrics for GERD in the near future.
Inter‐rater agreements between artificial intelligence (AI) and manual interpretations achieved excellent for individual numbers of reflux episodes and postreflux swallow‐induced peristaltic wave (PSPW): Intraclass correlation coefficient (ICC) was 0.965 and 0.921, respectively.
Laryngopharyngeal reflux (LPR) is a clinical conundrum without a diagnostic gold standard. The Esophageal Hypervigilance and Anxiety Scale (EHAS) is a questionnaire designed for cognitive-affective ...evaluation of visceral sensitivity. We hypothesized that esophageal hypervigilance and symptom-specific anxiety have an etiopathological role in generation of LPR symptoms, especially when gastroesophageal reflux disease (GERD) cannot explain these symptoms.
Consecutive patients with LPR and/or GERD symptoms lasting >3 months were prospectively enrolled and characterized using the Reflux Symptom Index, GERD questionnaire, and EHAS. Eligible patients with negative endoscopy underwent 24-hour impedance-pH monitoring off acid suppression for phenotyping GERD and assessment of reflux burden, using conventional metrics (acid exposure time and number of reflux episodes) and novel metrics (mean nocturnal baseline impedance and postreflux swallow-induced peristaltic wave index).
Of 269 enrolled patients (mean age 47.1 years, 21-65 years, 60.6% female), 90 patients were with concomitant GERD and LPR symptoms, 32 patients were with dominant LPR symptoms, 102 patients were with dominant GERD symptoms, and 45 were controls. Patients with concomitant GERD and LPR symptoms had higher EHAS than those with dominant GERD symptoms and controls ( P ≤ 0.001); patients with dominant LPR symptoms had higher EHAS than controls ( P = 0.007). On Pearson correlation, EHAS positively correlated with the Reflux Symptom Index.
Esophageal hypervigilance and symptom-specific anxiety may be more important than reflux burden in LPR symptom perception.
Background
Contractile segment impedance (CSI) obtained from high‐resolution impedance manometry (HRIM) is a measure of mucosal integrity that predicts gastroesophageal reflux disease (GERD). While ...straight leg raise (SLR) maneuver augments esophageal peristaltic vigor, it remains unclear whether SLR affects CSI values. This study was aimed to evaluate whether CSI with SLR is feasible and useful to complement the diagnosis of GERD.
Methods
We prospectively recruited 48 patients with typical GERD symptoms who underwent esophagogastroduodenoscopy, HRIM with SLR maneuver, and multichannel intraluminal impedance‐pH (MII‐pH) testing. The capability of mean nocturnal baseline impedance (MNBI), resting baseline impedance (RBI), CSI with or without SLR maneuver in predicting GERD was assessed using receiver operating characteristics (ROC) analysis.
Key Results
Among 20 GERD patients and 28 non‐GERD patients, all values of impedance‐based metrics were lower in GERD patients compared to non‐GERD patients (p < 0.001). For GERD identification, area under receiver operating characteristic curve (AUROC) values of CSI with SLR maneuver, CSI, MNBI, and RBI were 0.901, 0.858, 0.865, and 0.797. Particularly in ineffective esophageal motility (IEM) patients, SLR maneuver increased mean distal contractile integral from 436 to 828.7 mmHg.s.cm (p = 0.018) and enhanced AUROC values of CSI for GERD identification from 0.917 to 0.958.
Conclusions & Inferences
CSI measurement during HRIM appears to be a reliable, time‐saving, and less invasive tool for complementing GERD diagnosis. Our results also suggest a simple SLR maneuver during HRIM could enhance diagnostic accuracy of CSI for GERD identification especially in IEM patients.
Background/aim
The cold receptor, transient receptor potential melastatin 8 (TRPM8), has been reported to be expressed in esophageal vagal afferents. Esophageal infusion of menthol modulates ...esophageal perception in reflux patients via TRPM8, but the effects of menthol on esophageal motility are not well investigated. This study aimed to test the hypothesis whether the infusion of menthol into the esophagus could affect esophageal peristaltic characteristics.
Methods
Eighteen healthy adults (men 13, mean age 27) underwent high‐resolution manometry (HRM) using a catheter with the injection port located in mid‐esophagus. Primary peristalsis was performed with ten wet swallows, while secondary peristalsis was generated by 10 rapid air injections. Two different sessions were randomly performed including acute administration of menthol (3 mM) and the placebo.
Results
Menthol significantly decreased upper esophageal (UES) pressure of primary peristalsis than the placebo (p = 0.019). There was no difference in distal contractile integral (p = 0.33), distal latency (p = 0.86), basal lower esophageal sphincter pressure (p = 0.19), or 4‐second integrated relaxation pressure (p = 0.75) between menthol and placebo. Menthol significantly decreased the frequency of secondary peristalsis subsequent to the administration of menthol during rapid injections with 20 mL air (p = 0.04).
Conclusions
Intraluminal infusion of menthol reduces UES basal pressure and inhibits peristaltic frequency of secondary peristalsis. The data suggest that the triggering of secondary peristalsis is probably modulated by TRPM8‐sensitive mechanoreceptors; however, the activation of TRPM8 from menthol does not alter esophageal motility following deglutition or distension‐induced secondary peristalsis.
This study utilized HRM to evaluate the physiological effects of menthol on esophageal peristalsis in healthy adults. The results showed that esophageal infusion of menthol could inhibit peristaltic frequency of secondary peristalsis as induced by rapid air distension. Additionally, there appears to be a distinct effect of menthol on primary peristalsis characterized by reduced UES basal pressure.
Background and Aim
Opioid receptors agonists have been demonstrated to impair lower esophageal sphincter (LES) relaxation and induce spastic esophageal dysmotility, but little was known for their ...impact on distension‐induced secondary peristalsis. The aim of the study was to investigate the hypothesis whether acute administration of codeine can influence physiological characteristics of primary and secondary peristalsis in healthy adults.
Methods
Eighteen healthy volunteers (13 men, mean age 27.5 years, aged 20–43 years) underwent high resolution manometry (HRM) with a catheter containing an injection port in mid‐esophagus. Secondary peristalsis was performed with 10 and 20 mL rapid air injections. Two different sessions including acute administration of codeine (60 mg) or the placebo were randomly performed.
Results
Codeine significantly increased 4‐s integrated relaxation pressure (IRP‐4s) (P = 0.003) and shortened distal latency (DL) (P = 0.003) of primary peristalsis. The IRP‐4s of secondary peristalsis was also significantly higher after codeine than the placebo during air injections with 10 mL (P = 0.048) and 20 mL (P = 0.047). Codeine significantly increased the frequency of secondary peristalsis during air injections with 10 mL than the placebo (P = 0.007), but not for air injection with 20 mL (P = 0.305).
Conclusions
In addition to impair LES relaxation and reduce distal latency of primary peristalsis, codeine impairs LES relaxation of secondary peristalsis and increases secondary peristaltic frequency. Our study supports the notion in human esophagus that the impact of opioids on peristaltic physiology appears to be present in both primary and secondary peristalsis.
The GABA(B) receptor agonist baclofen is known to suppress the rate of spontaneous swallowing but not pharyngeal muscle contraction. The extent to which baclofen may alter volitional swallowing is ...not currently known. We investigated the effects of baclofen in healthy subjects, hypothesizing that baclofen exposure would alter volume‐regulation and/or piecemeal deglutition behaviors during volitional swallowing attempts. Pharyngeal high‐resolution manometry impedance (P‐HRM‐I) protocol was used to assess swallowing function of 22 healthy adult volunteers (median 29 years) who were investigated on two occasions, receiving 40 mg baclofen (oral) 1 h before study, or placebo (randomized). Standard swallow function variables recommended by the pharyngeal HRM Working Group were derived for 5 ml, 10 ml, and 20 ml volumes of thin and extremely thick liquid challenges. Multiple swallow behaviors, comprising two swallows <5 s apart, were characterized. The spontaneous swallow rate was also determined. Baclofen exposure had no overall significant effect on swallow variables. Upper esophageal sphincter pressure was weaker during exposure to baclofen, during both the pre‐deglutitive and post‐deglutitive phases of the swallow (p < 0.05 during thick liquid swallows). Piecemeal swallows, where the bolus is separated in two potions, were significantly more common during 20 ml boluses (p = 0.002). Baclofen decreased the frequency of piecemeal deglutition overall. Baclofen has limited to no effect on volitional swallowing measures, however, does reduce the likelihood of initiation of piecemeal deglutition to large volume challenges.
Background and Aim
Prucalopride, a high‐affinity 5‐hydroxytryptamine 4 receptor agonist, promotes esophageal peristalsis, while phosphodiesterase type 5 inhibitor sildenafil inhibits esophageal ...peristalsis. The present study was aimed to evaluate whether prucalopride would augment esophageal peristalsis subsequent to the application of sildenafil.
Methods
Seventeen healthy adults underwent high‐resolution manometry by a catheter with one injection port located in the mid‐esophagus. Secondary peristalsis was assessed by rapid air injections after water swallows. Two sessions were randomly performed including acute administration of sildenafil 50 mg after pretreatment with prucalopride or the placebo.
Results
The frequency of primary peristalsis subsequent to the administration of sildenafil was significantly increased by prucalopride (P = 0.02). Prucalopride also significantly increased distal contractile integral of primary peristalsis subsequent to the administration of sildenafil (P = 0.03). No difference in the frequency of secondary peristalsis subsequent to the administration of sildenafil for air injects of 10 mL (P = 0.14) or 20 mL (P = 0.21) was found between prucalopride and placebo. Prucalopride did not change distal contractile integral of secondary peristalsis subsequent to the administration of sildenafil for air injections of 10 mL (P = 0.09) or 20 mL (P = 0.12).
Conclusions
Prucalopride modulates sildenafil‐induced inhibition of primary peristalsis by increasing its effectiveness and peristaltic wave amplitude. Our findings suggest that activation of 5‐hydroxytryptamine 4 receptors plays a role in mediating sildenafil‐induced inhibition of esophageal primary peristalsis rather than secondary peristalsis.
Background/aim
Increased intra‐abdominal pressure from abdominal compression augments esophageal peristalsis during high‐resolution manometry (HRM), and straight leg raise (SLR) while supine ...increases intra‐abdominal pressure. We determined if water swallows performed during SLR can mimic contraction reserve seen with multiple rapid swallows (MRS).
Methods
Consecutive patients evaluated for GERD symptoms completed validated GERD questionnaires, esophageal HRM, and upper endoscopy. Distal contractile integral (DCI) was analyzed during single water swallows (10 × 5 mL), MRS (5 × 2 mL), and during SLR (5x5 mL). Peristaltic breaks were measured using software tools with a 20 mm Hg isobaric contour. Univariate correlational analyses were performed to compare esophageal motor patterns and DCI values during single water swallows, MRS, and SLR.
Results
Of 103 study patients (mean age: 46.7 ± 12.3 years, 56.3% female), 50 (48.5%) had ineffective esophageal motility (IEM). Contraction reserve was observed on MRS in 62% with IEM, and 35.8% with normal motility (p = 0.008). DCI was significantly higher during SLR compared to mean single swallow DCI in both IEM and normal motility patients (p < 0.001 for each comparison). In IEM patients, SLR significantly reduced swallows with peristaltic breaks (6.1 ± 3.7 vs 3.6 ± 3.6; p < 0.001) and shortened the length of the largest break (4.8 ± 3.4 vs 3.0 ± 3.0 cm; p < 0.001). DCI response following MRS correlated with DCI with swallows during SLR, with a correlational coefficient (Pearson's r) of 0.70 (p < 0.001).
Conclusions
Swallowing against the resistance of increased intra‐abdominal pressure from SLR improves esophageal body peristaltic performance and predicts esophageal body contraction reserve.
This study utilized HRM to investigate if water swallows during SLR can mimic contraction reserve seen with MRS. SLR not only increases esophageal body contractile vigor but also reduces swallows with peristaltic breaks. The result provides evidence that using SLR maneuver, findings similar to MRS can be obtained in patients with esophageal hypomotility.
Background:
Acid sensitivity can be altered in patients with gastroesophageal reflux disease (GERD). Secondary peristalsis helps clear gastro-esophageal refluxate and residual ingested food bolus.
...Objectives:
The aim of this study was to investigate the associations among acid sensitivity, esophageal mucosal integrity, chemical clearance, and secondary peristalsis before and after esophageal acid infusion.
Design:
This was an investigator-initiated, prospective, cross-sectional study.
Methods:
Adult reflux patients underwent high resolution manometry and 24 h impedance-pH monitoring off acid suppression to identify GERD phenotypes, including non-erosive reflux disease (NERD), reflux hypersensitivity (RH), and functional heartburn (FH). Secondary peristalsis was assessed using five rapid 20 mL air injections into the esophagus before and after infusion of hydrochloric acid (0.1 N) into the mid-esophagus. Conventional acid infusion parameters recorded included lag time, intensity rating, and sensitivity score. Chemical clearance was evaluated using the post-reflux swallow-induced peristaltic wave (PSPW), and mucosal integrity was assessed by the mean nocturnal baseline impedance (MNBI) derived from impedance-pH monitoring.
Results:
A total of 88 patients (age 21–64 years, 62.5% women) completed the study including 12 patients with NERD, 45 with RH, and 31 with FH. There was no significant difference in acid infusion parameters between patients with NERD, RH, and FH. Upon acid infusion, patients who exhibited successful secondary peristalsis had longer lag time, higher MNBI, and shorter bolus contact time than those without secondary peristalsis. Meanwhile, patients with intact PSPW demonstrated significantly higher intensity ratings in response to acid perfusion and higher MNBI than those with impaired PSPW. The lag time correlated positively with MNBI (r = 0.285; p = 0.007).
Conclusion:
In conclusion, the protective effect of esophageal secondary peristalsis and chemical clearance on esophageal mucosal integrity was demonstrated. Concerning acid sensitivity, longer lag time in patients with intact secondary peristalsis may be attributed to better esophageal mucosal integrity, while stronger intensity ratings may have a greater tendency to induce PSPW and protect esophageal mucosal integrity.
