The Utility of Novel pH-Impedance Monitoring Parameters (PSPW Index and MNBI) in Pediatric Gastroesophageal Reflux Disease Phenotypes-A Systematic Review.

Background/Objectives: Researchers have proposed two novel impedance-pH parameters, mean nocturnal baseline impedance (MNBI) and the post-reflux swallow-induced peristaltic wave (PSPW) index, to enhance the diagnosis of gastroesophageal reflux disease (GERD) and enable better predictions of the effectiveness of anti-reflux therapies. This systematic review aims to synthesize the available evidence on the utility of the PSPW index and MNBI as diagnostic tools for pediatric GERD. Methods: A systematic search of studies reporting PSPW index and MNBI values in patients with GERD was performed in PubMed, Embase, Clarivate, Scopus, Cochrane and Google Scholar databases from their beginning until April 2024. The following terms were used: GERD, children, pediatric, PSPW and MNBI. Results: Eight studies were included, describing 479 patients ranging from 2 months to 17 years old over an 8-year period in 12 pediatric centers. Four studies demonstrated that children with pathological acid exposure have a significantly lower MNBI, with a good discriminatory ability to diagnose GERD. The PSPW index showed lower values in patients with reflux hypersensitivity (RH) compared to those with functional heartburn (FH). Conclusions: Patients with pathological acid exposure tend to exhibit lower MNBI and PSPW index values compared to those with normal acid exposure. MNBI and the PSPW index show promise as diagnostic tools in distinguishing between different GERD phenotypes. Further research is needed to establish standardized diagnostic criteria and optimize the clinical applicability in GERD diagnosis and management.

Proximal esophageal impedance baseline increases the yield of impedance-pH and is associated with response to PPIs in chronic cough patients.

BACKGROUND: Chronic cough significantly impairs the quality of life. Although various studies focused on MNBI as assessed in the distal esophagus, scarce data are available on the clinical value of proximal measurements. AIM: To investigate the role of proximal MNBI in the workup of patients with chronic cough and its ability to predict PPI response. METHODS: Demographic, clinical, endoscopy findings, impedance-pH and HRM tracings from consecutive cough patients were evaluated. MNBI was calculated at proximal and distal esophagus. RESULTS: One hundred and sixty four patients were included. In addition to traditional variables, when considering also the PSPW index or MNBI at 3 cm or 15 cm, the proportion of patients with pathological impedance-pH monitoring significantly increased. 70/164 patients were responders, while 94 (57.3%) were non-responder to double PPI dose (p < 0.05). Patients with pathologic MNBI at 3 cm and/or 15 cm as well as those with pathologic PSPW index were characterized by a significantly higher proportion of responders than that observed among patients with normal impedance-pH variables (p < 0.001). The proportion of responders with pathological MNBI at 15 cm was significantly higher than the proportion of responders with pathological MNBI at 3 cm (82.8% vs. 64.3%, p < 0.05). At multivariable model, pathological MNBI at both 3 cm and 15 cm as well as PSPW index were associated with PPI responsiveness. The strongest association with PPI response was observed for MNBI at 15 cm. CONCLUSIONS: The assessment of MNBI at proximal esophagus increases the diagnostic yield of impedance-pH monitoring and may represent a useful predictor of PPI responsiveness in the cumbersome clinical setting of suspected reflux-related cough.

Association between Mean Nocturnal Baseline Impedance (MNBI) and Post-Reflux Swallow-Induced Peristaltic Wave Index (PSPW) in GERD Patients.

Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal disorders in the world. Two parameters, mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave index (PSPW), have been recently proposed to help differentiate GERD phenotypes. Our study aimed to assess whether there is any correlation between the two parameters, while also taking a look at their ability to distinguish between GERD phenotypes. We recruited 81 patients who were divided into 4 groups based on their GERD phenotype: erosive reflux disease (ERD), non-erosive reflux disease (NERD), reflux hypersensitivity (RH), and functional heartburn (FH). Both MNBI (AUROC 0.855) and PSPW (AUROC 0.835) had very good performances in separating ERD patients from non-ERD patients. PSPW (AUROC 0.784) was superior to MNBI (AUROC 0.703) in distinguishing NERD patients from patients with RH or FH. The PSPW index (AUROC 0.762) was more effective than MNBI (AUROC 0.668) in separating RH from FH. We found that PSPW and MNBI have a strong statistical correlation (Pearson correlation coefficient, r = 0.722, p < 0.001). Furthermore, PSPW predicted pathological MNBI (<2292 Ω) with good performance (AUROC 0.807). MNBI and PSPW are useful in distinguishing GERD phenotypes, with a strong correlation between the two parameters.

Towards a better diagnosis of gastro esophageal reflux disease.

INTRODUCTION: GERD is a common disorder and is characterized by the presence of typical or atypical symptoms. In GERD patients, the presence of mucosal alterations in endoscopy is detected in up to 30% of individuals. The clinical presentation of GERD patients may be complex and their management is challenging, due to the heterogeneous clinical presentation. The present review has been performed searching all relevant articles in this field, over the past years, using PubMed database. AREAS COVERED: The diagnosis and management of GERD have been significantly improved in the last years due to the increasing availability of reflux monitoring techniques and the implementation of new procedures in the therapeutic armamentarium. Beside traditional impedance-pH variables, new metrics have been developed, increasing the diagnostic yield of reflux monitoring and better predicting the treatment response. Traditional pharmacological treatments include acid-suppressive-therapy and/or anti-acid. On the other hand, surgical treatment and, more recently, endoscopic procedures represent a promising field in the therapeutic approach. EXPERT OPINION: Diagnosis and treatment of GERD still represent a challenging area. However, we believe that an accurate upfront evaluation is, nowadays, necessary in addressing patients with GERD to a more accurate diagnosis as well as to the best treatment options.

Novel Impedance-pH Parameters in Pre-Bariatric Assessment of Patients: A Pilot Study.

Novel impedance-pH parameters, Mean Nocturnal Baseline Impedance (MNBI) and Post-Reflux Swallow-Induced Peristaltic Wave (PSPW) index, have been proposed to improve the gastro-esophageal reflux disease (GERD) diagnostic yield. This study aims to determine the integrity of the esophageal epithelial barrier and chemical clearance using these novel parameters and to correlate them with acid exposure time (AET) and acid clearance time (ACT) in obese patients who are candidates for bariatric surgery (BS). Twenty impedance-pHmetry tracings of patients prior to BS were reviewed. Nine (45%) patients with a conclusive diagnosis of GERD had significantly higher ACT, lower MNBI in the distal esophagus and lower PSPW indexes compared to obese patients without GERD. Moreover, 100% of obese patients with GERD had a pathological ACT compared to obese patients without GERD (p = 0.003). However, the percentage of pathological MNBI and PSPW index did not differ between obese patients with and without GERD. The PSPW index and MNBI of the distal channel significantly correlated with ACT and AET. Further studies are needed to assess the role of time-consuming novel parameters in the routine evaluation of morbidly obese patients candidates for BS. The value of acid clearance time is confirmed as a relevant impedance-pH parameter in these patients.

On-therapy impedance-pH monitoring can efficiently characterize PPI-refractory GERD and support treatment escalation.

BACKGROUND: On-therapy impedance-pH monitoring is recommended in patients with documented GERD and PPI-refractory heartburn in order to establish whether the unremitting symptom is reflux-related or not. AIMS: To define on-PPI cut-offs of impedance-pH metrics allowing proper interpretation of on-therapy impedance-pH monitoring. METHODS: Blinded expert review of impedance-pH tracings performed during double-dosage PPI, prospectively collected from 150 GERD patients with PPI-refractory heartburn and 45 GERD patients with PPI-responsive heartburn but persisting extra-esophageal symptoms. Acid exposure time (AET), number of total refluxes (TRs), post-reflux swallow-induced peristaltic wave (PSPW) index, and mean nocturnal baseline impedance (MNBI) were assessed. On-PPI cut-offs were defined and evaluated with ROC analysis and the area under curve (AUC). RESULTS: All the four impedance-pH metrics significantly differed between PPI-refractory and PPI-responsive heartburn cases. At ROC analysis, AUC was 0.73 for AET, 0.75 for TRs, 0.81 for PSPW index, and 0.71 for MNBI; best cut-offs were ≥1.7% for AET, ≥45 for TRs, ≤36% for PSPW index, and ≤ 1847 Ω for MNBI; AUC of such cut-offs was 0.66, 0.71, 0.73, and 0.68, respectively. Analysis of PSPW index and MNBI added to assessment of AET and TRs significantly increased the yield of on-therapy impedance-pH monitoring in the PPI-refractory cohort (97% vs. 83%, p < 0.0001). Notably, suboptimal acid suppression as shown by AET ≥1.7% was detected in 43% of 150 PPI-refractory cases. CONCLUSIONS: We have defined on-PPI cut-offs of impedance-pH metrics by which comprehensive assessment of impedance-pH tracings, including analysis of PSPW index and MNBI can efficiently characterize PPI-refractory GERD and support treatment escalation.

Clinical use of mean nocturnal baseline impedance and post-reflux swallow-induced peristaltic wave index for the diagnosis of gastro-esophageal reflux disease.

The clinical diagnosis of gastro-esophageal reflux disease (GERD) is based on the presence of typical esophageal troublesome symptoms. In clinical practice, heartburn relief following a proton pump inhibitor (PPI) trial or endoscopy can confirm a diagnosis of GERD. In cases of diagnostic uncertainty or before anti-reflux interventions, combined impedance-pH monitoring (MII-pH) provides a comprehensive assessment of both physical and chemical properties of the refluxate, allowing to achieve a conclusive diagnosis of GERD. Recently, the Lyon Consensus proposed the use of mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave index (PSPW-I) as novel MII-pH metrics to support the diagnosis of GERD. The calculation of MNBI and PSPW-I currently needs to be performed manually, but artificial intelligence systems for the automated analysis of MII-pH tracings are being developed. Several studies demonstrated the increased diagnostic yield MNBI and PSPW-I for the categorization of patients with GERD at both on- and off-PPI MII-pH monitoring. Accordingly, we performed a narrative review on the clinical use and diagnostic yield of MNBI and PSPW-I when the diagnosis of GERD is uncertain. Based on currently available evidence, we strongly support the evaluation of PSPW-I and MNBI as part of the standard assessment of MII-pH tracings for the evaluation of GERD, especially in patients with endoscopy-negative heartburn.

Reflux characteristics triggering post-reflux swallow-induced peristaltic wave (PSPW) in patients with GERD symptoms.

BACKGROUND: Esophageal chemical clearance has been evaluated with the post-reflux swallow-induced peristaltic wave (PSPW) index. The factors triggering PSPW in Gastro-esophageal reflux disease (GERD) have not yet been investigated. This multicenter study was aimed at evaluating the characteristics of reflux episodes associated with PSPW occurrence in patients with typical GERD symptoms. METHODS: Impedance-pH tracings from patients with typical reflux symptoms were analyzed. Sixteen healthy subjects were included for comparison. Multivariate analysis was performed to determine predictors of PSPW events. KEY RESULTS: Impedance-pH tracings from 60 patients and 16 healthy subjects were evaluated. A total of 3454 refluxes were recorded. In patients, comparing reflux episodes followed with those not followed by a PSPW, significantly higher proportions of acid (79% vs. 74%, p: 0.02), mixed (47% vs. 32%, p: 0.0001) and proximal refluxes (34% vs. 20%, p: 0.0001) were observed. A multivariate analysis, acid (OR: 1.3, 95% CI: 1.05-1.6), mixed (OR: 2, 95% CI: 1.6-2.3), and proximal (OR: 2.1, 95% CI: 1.7-2.5) refluxes were independently associated with PSPWs. Reflux episodes followed by a PSPW were characterized by a significantly higher bolus clearing time [(mean ± SD) 41 s ± 6 s vs. 30 s ± 5 s, p < 0.05] whereas nadir pH value of reflux events preceding PSPWs was tangentially but not significantly lower [(mean ± SD) 2.61 ± 1.22 vs. 2.74 ± 1.26, p: 0.057]. CONCLUSIONS AND INFERENCES: Acid, mixed and proximal refluxes, and their duration are key factors in eliciting PSPWs. PSPW represents a response to reflux directly related to the potential harmfulness of reflux contents.

Postreflux swallow-induced peristaltic wave index from pH-impedance monitoring associates with esophageal body motility and esophageal acid burden.

BACKGROUND: Postreflux swallow-induced peristaltic wave (PSPW) on pH-impedance monitoring and contraction vigor on high-resolution manometry (HRM) both assess esophageal peristaltic response. We aimed to evaluate relationships between PSPW and esophageal peristalsis on HRM in the context of reflux disease in this multicenter cohort study. METHODS: pH-impedance and HRM studies performed on patients with persisting reflux symptoms were reviewed from 6 centers (5 in Europe and 1 in US). Total, upright and supine acid exposure time (AET) were evaluated from pH-impedance studies; PSPW index (PSPWI) and mean nocturnal baseline impedance (MNBI) were calculated using standard methodology. Esophageal body contraction vigor was analyzed using distal contractile integral (DCI), and DCI ratio > 1 between single swallows and multiple rapid swallows (MRS) defined presence of contraction reserve. Student's t test, ANOVA, and linear regression were utilized to investigate relationships between PSPW, contraction vigor, and contraction reserve. KEY RESULTS: Of 296 patients (52.8 ± 0.8 yr, 63% F), median PSPWI was 0.475. Only 24.0% had intact DCI; the remainder had varying degrees of hypomotility. As hypomotility increased, PSPWI and MNBI decreased significantly, while total AET and reflux episodes had an inverse response (P ≤ .002 for each). MRS data were available in 167 (56.4%), 72.5% had contraction reserve. MRS cohorts with normal PSPWI had significantly lower reflux burden compared to low PSPWI, regardless of presence or absence of contraction reserve (P ≤ .001). CONCLUSIONS AND INFERENCES: PSPWI correlates with esophageal hypomotility and reflux burden, and complements clinical reflux evaluation. Intact PSPW is more relevant to esophageal reflux clearance than contraction reserve.

Advances in the diagnosis of GERD.

Gastroesophageal reflux disease (GERD) is considered one of the most frequent chronic gastrointestinal diseases globally with high costs due to treatment and investigations.First line therapy is with proton pump inhibitors, those who do not respond to initial treatment usually require further investigations such as upper gastrointestinal endoscopy or ambulatory 24-hours esophageal pH monitoring. The total time of exposure to acid and the DeMeester score represent the most useful parameters associated with conventional pH-metry, because they can identify gastroesophageal reflux disease.Although pH-metry is considered the gold standard for the evaluation of gastroesophageal reflux disease, new impedance-based parameters have been introduced in recent years with the role of increasing the accuracy of diagnosing gastroesophageal reflux disease and characterizing the type of reflux. The development of multichannel intraluminal pH-impedance has improved the ability to detect and quantify gastroesophageal reflux. New parameters such as post-reflux swallowing peristaltic wave (PSPW) index and the mean nocturnal basal impedance (MNBI) have recently been introduced to assess GERD phenotypes more accurately. This review evaluates current GERD diagnotic tools while also taking a brief look at newer diagnostic parameters like PSPW and MNBI.

Bile reflux in patients with nerd is associated with more severe heartburn and lower values of mean nocturnal baseline impedance and chemical clearance.

BACKGROUND: Mean nocturnal baseline impedance (MNBI) and postreflux swallow-induced peristaltic wave (PSPW) index are novel impedance-based markers of reflux, but the effect of bile reflux on these metrics is unknown. The aim of this study was to evaluate bile reflux, MNBI, and PSPW index in patients with endoscopy-negative GERD partially responsive to PPI therapy. METHODS: All patients underwent off-PPI endoscopy, esophageal manometry, multichannel intraluminal impedance pH (MII-pH), and bile reflux monitoring. Abnormal esophageal acid exposure time (AET) was required for inclusion. Symptom intensity (using 10-cm visual analog scales), and conventional and novel MII-pH metrics were compared between patients with and without abnormal bile reflux. KEY RESULTS: We evaluated 42 NERD patients (29 males, mean age: 53.4 ± 13. years), mean AET 6.1 ± 2%, of which 21 had abnormal bile reflux (Group A, 10.2 ± 4.9%), and 21 had normal bile reflux (Group B, 0.4 ± 0.1%, P < .05 compared with Group A). Heartburn reporting on PPI was higher in Group A (7.2 ± 2.1 vs 5.8 ± 0.9; P = .002), but AET, number of reflux events (acidic and weakly acidic), did not differ between the two groups. However, both PSPW index and MNBI were lower in Group A (P < .001). A strong inverse linear correlation was found between bile reflux and both MNBI (Pearson's test; R = -0.714; P < .001) and PSPW index (R = -0.722; P < .001). CONCLUSIONS AND INFERENCES: Compared to acid reflux alone, the presence of bile in an acidic esophageal environment is associated with more severe heartburn, lesser relief from PPI therapy, higher impairment of esophageal mucosal integrity and less effective chemical clearance.

Diagnosis of gastroesophageal reflux: an update on current and emerging modalities.

Gastroesophageal reflux disease (GERD) is a common condition characterized by troublesome symptoms or esophageal mucosal lesions attributed to excessive esophageal acid exposure. Various pathophysiological mechanisms account for GERD, including impaired esophageal peristalsis and anatomical or physiological defects at the esophagogastric junction (EGJ). Endoscopy identifies GERD complications and detects potential alternative diagnoses. However, if symptoms persist despite proton pump inhibitor therapy, functional esophageal tests are useful to characterize reflux burden and define the symptom association profile. Ambulatory pH or pH-impedance monitoring measures the 24-h acid exposure time, which remains the most reproducible reflux metric and predicts response to antireflux therapy. Apart from identifying peristaltic dysfunction, esophageal high-resolution manometry defines the morphology and contractile vigor (EGJ-CI) of the EGJ. Novel metrics obtained from pH-impedance monitoring include the postreflux swallow-induced peristaltic wave index and mean nocturnal baseline impedance, which augment the diagnostic value of pH-impedance testing. Mucosal impedance can also be recorded using a probe inserted through a gastroscope, or a novel balloon catheter with arrays of impedance electrodes inserted following sedated endoscopy. The latest developments in functional esophageal tests define the GERD phenotype based on pathogenesis, reflux exposure, structural or motility disorders, and symptom burden, facilitating appropriate treatment.

Impedance-pH Monitoring for Diagnosis of Reflux Disease: New Perspectives.

Heartburn is the most specific symptom of gastroesophageal reflux disease (GERD). In clinical practice, heartburn relief by a proton pump inhibitor (PPI) trial does suffice to confirm GERD. However, an objective diagnosis of GERD is required before anti-reflux endoscopic or surgical interventions, independently from PPI response. Thus, since normal findings at upper endoscopy are detected in the majority of patients with heartburn, reflux monitoring is often required. When traditional catheter-based or wireless pH tests are used, reflux episodes are conventionally identified by pH drops below 4.0 units. Combined impedance-pH monitoring has the advantage to provide a comprehensive assessment of both physical and chemical properties of refluxate and the distinction between acid and weakly acidic refluxes, both proven to cause heartburn. Unfortunately, the conventional impedance-pH parameters, namely acid exposure time and number of reflux events, are characterized by suboptimal diagnostic sensitivity, and the reliability of symptom-reflux association indexes remains questionable. Therefore, novel impedance parameters, namely the post-reflux swallow-induced peristaltic wave (PSPW) index and the mean nocturnal baseline impedance (MNBI), have recently been proposed in order to achieve a better diagnostic yield. In fact, they proved to be highly accurate in distinguishing reflux-related from reflux-unrelated heartburn, off- as well as on-PPI therapy. Currently, manual review of impedance-pH tracings is needed because of the modest accuracy of available software tools for automated analysis. PSPW index and MNBI are highly applicable and reproducible, and their calculation requires a few additional minutes during the manual review of impedance-pH tracings. So far, we believe that PSPW index and MNBI are ready for prime time and should become part of the standard analysis of impedance-pH tracings for GERD diagnosis in patients with endoscopy-negative heartburn.

Esophageal chemical clearance and baseline impedance values in patients with chronic autoimmune atrophic gastritis and gastro-esophageal reflux disease.

BACKGROUND: The factors influencing new markers of gastro-esophageal reflux disease detected by impedance-pH monitoring - mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave (PSPW) index - need to be evaluated. AIM: To compare endoscopy-negative heartburn with chronic autoimmune atrophic gastritis (CAAG). MATERIALS AND METHODS: 24 patients with CAAG, 25 with non-erosive reflux disease (NERD) and 25 with functional heartburn (FH) were included. In all patients the main impedance-pH monitoring parameters were calculated. RESULTS: CAAG and NERD patients had a number of reflux events (non-acid ones being more common among the former group) which was higher than that found in FH (p<0.001). MNBI decreased progressively in FH (>3000Ohm), CAAG (>2000Ohm) and NERD (<1000Ohm) patients (p=0.0046). The PSPW index was similar between CAAG and NERD patients but significantly lower in comparison to FH (p<0.0001). CONCLUSION: Patients with CAAG have evidence of non-acid reflux based on the high number of reflux events and confirmed by low values of MNBI and PSPW index. MNBI is a strong marker of acid/non-acid reflux-induced mucosal damage, whereas the PSPW index can reliably discriminate patients with reflux from those with FH, independently of the acidity of refluxate.

Recent advances in diagnostic testing for gastroesophageal reflux disease.

INTRODUCTION: Gastroesophageal reflux disease (GERD) has a large economic burden with important complications that include esophagitis, Barrett's esophagus, and adenocarcinoma. Despite endoscopy, validated patient questionnaires, and traditional ambulatory pH monitoring, the diagnosis of GERD continues to be challenging. Areas covered: This review will explore the difficulties in diagnosing GERD with a focus on new developments, ranging from basic fundamental changes (histology and immunohistochemistry) to direct patient care (narrow-band imaging, impedance, and response to anti-reflux surgery). We searched PubMed using the noted keywords. We included data from full-text articles published in English. Further relevant articles were identified from the reference lists of review articles. Expert commentary: Important advances in novel parameters in intraluminal impedance monitoring such as baseline impedance monitoring has created some insight into alternative diagnostic strategies in GERD. Recent advances in endoscopic assessment of esophageal epithelial integrity via mucosal impedance measurement is questioning the paradigm of prolonged ambulatory testing for GERD. The future of reflux diagnosis may very well be without the need for currently employed technologies and could be as simple as assessing changes in epithelia integrity as a surrogate marker for GERD. However, future studies must validate such an approach.

The Relationship of the Post-reflux Swallow-induced Peristaltic Wave Index and Esophageal Baseline Impedance with Gastroesophageal Reflux Disease Symptoms.

BACKGROUND/AIMS: The post-reflux swallow-induced peristaltic wave (PSPW) index and esophageal baseline impedance (BI) are novel impedance parameters used to evaluate esophageal chemical clearance and mucosal integrity. However, their relationship with reflux symptoms is not known. We aim to evaluate the correlations of PSPW index and esophageal BI with gastroesophageal reflux disease (GERD) symptoms. METHODS: We performed a retrospective review of multichannel intraluminal impedance and pH (MII-pH) tracings in patients with suspected GERD. Reflux symptoms were also analyzed from checklists using ordinal scales. The PSPW index and esophageal BIs in 6 spots (z1-z6) were measured. Bivariate (Spearman) correlation was used to analyze the relationship between the PSPW index or esophageal BI, and the degree of GERD symptoms measured. RESULTS: The MII-pH records of 143 patients were analyzed. The PSPW index was significantly lower in patients who had heartburn and negatively correlated with the degree of heartburn (r = -0.186, P < 0.05). On the contrary, the PSPW index was not significantly correlated with the degree of dysphagia (r = -0.013, P = 0.874). Distal esophageal BI was not significantly correlated with heartburn, but negatively correlated with the degree of dysphagia (z3: r = -0.328, z4: r = -0.361, z5: r = -0.316, z6: r = -0.273; P < 0.05). CONCLUSIONS: These findings suggest that delayed chemical clearance of the esophagus may induce heartburn, but that it is not related to dysphagia. However, a lack of esophageal mucosal integrity may be related to dysphagia.

Manually calculated oesophageal bolus clearance time increases in parallel with reflux severity at impedance-pH monitoring.

BACKGROUND: Oesophageal clearance has been scarcely studied. AIMS: Oesophageal clearance in endoscopy-negative heartburn was assessed to detect differences in bolus clearance time among patients sub-grouped according to impedance-pH findings. METHODS: In 118 consecutive endoscopy-negative heartburn patients impedance-pH monitoring was performed off-therapy. Acid exposure time, number of refluxes, baseline impedance, post-reflux swallow-induced peristaltic wave index and both automated and manual bolus clearance time were calculated. Patients were sub-grouped into pH/impedance positive (abnormal acid exposure and/or number of refluxes) and pH/impedance negative (normal acid exposure and number of refluxes), the former further subdivided on the basis of abnormal/normal acid exposure time (pH+/-) and abnormal/normal number of refluxes (impedance+/-). RESULTS: Poor correlation (r=0.35) between automated and manual bolus clearance time was found. Manual bolus clearance time progressively decreased from pH+/impedance+ (42.6s), pH+/impedance- (27.1s), pH-/impedance+ (17.8s) to pH-/impedance- (10.8s). There was an inverse correlation between manual bolus clearance time and both baseline impedance and post-reflux swallow-induced peristaltic wave index, and a direct correlation between manual bolus clearance and acid exposure time. A manual bolus clearance time value of 14.8s had an accuracy of 93% to differentiate pH/impedance positive from pH/impedance negative patients. CONCLUSIONS: When manually measured, bolus clearance time reflects reflux severity, confirming the pathophysiological relevance of oesophageal clearance in reflux disease.