How to diagnose GERC more effectively: reflections on post-reflux swallow-induced peristaltic wave index and mean nocturnal baseline impedance.

INTRODUCTION: Post-reflux swallow-induced peristaltic wave index (PSPWI) and mean nocturnal baseline impedance (MNBI) are novel parameters reflect esophageal clearance capacity and mucosal integrity. They hold potential in aiding the recognition of gastroesophageal reflux-induced chronic cough (GERC). Our study aims to investigate their diagnostic value in GERC. METHODS: This study included patients suspected GERC. General information and relevant laboratory examinations were collected, and final diagnosis were determined following guidelines for chronic cough. The parameters of multichannel intraluminal impedance-pH monitoring (MII-pH) in patients were analyzed and compared to explore their diagnostic value in GERC. RESULTS: A total of 186 patients were enrolled in this study. The diagnostic value of PSPWI for GERC was significant, with the area under the working curve (AUC) of 0.757 and a cutoff value of 39.4%, which was not statistically different from that of acid exposure time (AET) (p > 0.05). The combined diagnostic value of AET > 4.4% and PSPWI < 39.4% was superior to using AET > 4.4% alone (p < 0.05). Additionally, MNBI and distal MNBI also contributed to the diagnosis of GERC, with AUC values of 0.639 and 0.624, respectively. AET > 4.4% or PSPWI < 39.4% is associated with a 44% reduction in missed diagnoses of non-acid GERC compared to AET > 6.0% or symptom association probability (SAP) ≥ 95%, and may be more favorable for identifying GERC. CONCLUSION: The diagnostic value of PSPWI for GERC is comparable to that of AET. Combining PSPWI < 39.4% or AET > 4.4% can improve the diagnostic efficiency by reducing the risk of missed diagnoses in cases where non-acid reflux is predominant. Distal MNBI and MNBI can serve as secondary reference indices in the diagnosis of GERC.

Post-reflux swallow-induced peristaltic wave index: a new parameter for the identification of non-acid gastroesophageal reflux-related chronic cough.

BACKGROUND: The current available diagnostic criteria for gastroesophageal reflux-related chronic cough (GERC) dominated by non-acid reflux is imperfect. The post-reflux swallow-induced peristaltic wave index (PSPWI) is a parameter reflecting esophageal clearance function. OBJECTIVES: This study aims to investigate its diagnostic value for non-acid GERC. DESIGN: This study sought to compare the diagnostic value of PSPWI in different types of GERC, particularly non-acid GERC, and explore the clinical significance of PSPWI in the diagnosis of non-acid GERC through diagnostic experiments. METHODS: A retrospective analysis was performed based on 223 patients with suspected GERC who underwent multichannel intraluminal impedance-pH monitoring (MII-pH) in the outpatient clinic of our department from August 2016 to June 2021. Their clinical information, laboratory test results, and treatment responses were assessed and the underlying etiologies of chronic cough were categorized. The predictive value of the PSPWI in diagnosing different types of GERC, especially non-acid GERC, was analyzed and compared. RESULTS: A total of 195 patients with chronic cough who met the inclusion criteria underwent MII-pH monitoring. 143 patients had a definitive diagnosis of GERC, including 98 with acid GERC and 45 with non-acid GERC. The diagnostic value of PSPWI alone was moderate for GERC with an area under the working curve (AUC) 0.760, but poor for non-acid GERC with an AUC of 0.569. However, PSPWI < 39.8% combining with acid exposure time (AET) ⩽ 6.2% demonstrated a moderate diagnostic value for non-acid GERC, with an AUC of 0.722. When PSPWI < 39.8% combined with a non-acid reflux ratio >68.75%, the diagnostic value for non-acid GERC was improved (AUCROC = 0.80 versus AUCROC = 0.722, p < 0.05), which was significantly superior to non-acid symptom index (AUCROC = 0.804 versus AUCROC = 0.550, p < 0.05) and non-acid symptom association probability (AUCROC = 0.804 versus AUCROC = 0.571, p < 0.05). CONCLUSION: PSPWI < 39.8% and AET ⩽ 6.2% have demonstrated good diagnostic value for non-acid GERC. The diagnostic value was further improved when combined with non-acid reflux ratio >68.75%.

Novel Diagnostic Techniques in the Evaluation of Gastroesophageal Reflux Disease (GERD).

In our present clinical paradigm, patient symptoms and presentation in the setting of traditional findings from endoscopy (erosive esophagitis, Barrett's esophagus, reflux-mediated stenosis), esophageal high-resolution manometry, and/or ambulatory reflux monitoring (distal esophageal acid exposure time, numbers of reflux events, reflux-symptom association) guide the care of patients with suspected GERD. However, novel metrics and techniques acquired from or performed at endoscopy, manometry, or pH-impedance monitoring, beyond conventional evaluation, are of great interest to the gastroenterology community given the frequent (and sometimes challenging) presentation of suspected GERD. These novel and evolving diagnostic approaches have the potential to enhance the evaluation of these patients and optimize their management. In this invited review, we discuss the present evidence and potential clinical utility of selected GERD metrics and techniques of interest at endoscopy (dilated intercellular spaces, mucosal impedance), manometry (contractile integral, impedance analysis, straight leg raise, multiple rapid swallow maneuvers), and reflux monitoring (mean nocturnal baseline impedance, post-reflux swallow-induced peristaltic wave indices), and how these tools may be most optimally adopted and utilized for clinical care (Fig. 1).

Application of Artificial Intelligence in Measuring Novel pH-Impedance Metrics for Optimal Diagnosis of GERD.

Novel metrics extracted from pH-impedance monitoring can augment the diagnosis of gastroesophageal reflux disease (GERD). Artificial intelligence (AI) is being widely used to improve the diagnostic capabilities of various diseases. In this review, we update the current literature regarding applications of artificial intelligence in measuring novel pH-impedance metrics. AI demonstrates high performance in the measurement of impedance metrics, including numbers of reflux episodes and post-reflux swallow-induced peristaltic wave index and, furthermore, extracts baseline impedance from the entire pH-impedance study. AI is expected to play a reliable role in facilitating measuring novel impedance metrics in patients with GERD in the near future.

Esophageal chemical clearance and mucosa integrity values in refractory gastroesophageal reflux disease patients with different esophageal dynamics.

OBJECTIVES: Esophageal post-reflux swallow-induced peristaltic wave index (PSPWI) and mean nocturnal baseline impedance (MNBI), novel impedance-based markers of reflux burden, are associated with esophageal dynamics. We aim to investigate the characteristics of PSPWI and MNBI in Chinese refractory gastroesophageal reflux disease (RGERD) patients with different esophageal dynamic changes. MATERIALS AND METHODS: 201 RGERD and 76 functional heartburn patients, undergone off-PPI endoscopy, esophageal manometry and impedance-pH monitoring, were included. Comparisons of conventional and novel impedance-pH metrics were made among different esophageal dynamics groups. Receiver operating-characteristic analyses were utilized to evaluate the diagnostic efficacy of PSPWI and MNBI in differentiating abnormal esophageal dynamics. Correlations were used to investigate their associated factors. RESULTS: PSPWI and MNBI of RGERD with esophagogastric junction (EGJ) injury and esophageal dysmotility were lower than EGJ injury alone or normal dynamics (p < 0.05 for both comparisons). PSPWI with esophageal peristalsis abnormality was lower than EGJ injury (p = 0.049), while MNBI showed no statistical difference. PSPWI, MNBI and their combination have auxiliary diagnostic values for esophageal peristalsis [area under the curves (AUCs): 0.683, 0.656, 0.708)] while only their combination for EGJ injury (AUC: 0.610). And they positively correlated with esophageal motility while negatively correlated with ineffective swallows and acid reflux events. CONCLUSIONS: PSPWI and MNBI, indicating impairment of esophageal chemical clearance and mucosa integrity, were lower in RGERD patients with multiple esophageal dynamic injuries than single injuries or normal dynamics. Moreover, they provided useful contributing information for potential dynamic injuries if manometry has already been found normal or marginal.

Difference in meal-related esophageal intraluminal impedance change between gastroesophageal reflux disease and functional disorders.

OBJECTIVES: Gastroesophageal reflux disease (GERD) has overlapping symptoms with functional disorders such as functional heart burn. Twenty-four-hour pH with impedance monitoring is useful for differentiation. The intraluminal impedance change with meal in distal esophagus is not investigated. METHODS: We performed a retrospective investigation of clinical files, 24-hour pH with intraluminal impedance monitoring in patients with GERD and functional disorders. The post-reflux swallow induced peristaltic wave (PSPW) index as well as the impedance in distal esophagus before the first meal and 30 min and 60 min after the meal were measured and analyzed. RESULTS: A significant decrease of intraluminal impedance in distal esophagus was noted at 30 min (ΔI30min -301.5 [747.5] Ω, p = 0.018) and recovered at 60 min (ΔI60min -194.6 [766.0] Ω, p = 0.126) after meals in GERD patients. On the other hand, there was no significant change of impedance in patients with functional disorders. There were positive correlations between ΔI30min and PSPW index (correlation = 0.232, p = 0.038). Comparing GERD to functional disorders, the best cut-off value for ΔI30min was -212Ω with 74.4% sensitivity and 60.5% specificity. CONCLUSIONS: The intraluminal impedance in distal esophagus was lowered after meals in GERD patients other than functional disorders. This impedance change was correlated with PSPW index and could help differentiate GERD from functional disorders.

Sex-Based Differences in pH Parameters and Esophageal Impedance of Patients With Gastroesophageal Reflux Disease.

Background/Aims: The incidence of reflux esophagitis (RE) has a striking predominance in males. Conversely, non-erosive reflux disease (NERD) is more common in females. This imbalance of gastroesophageal reflux disease (GERD) implies sex-related differences in its pathogenesis. However, limited studies have analyzed the sex-based differences in pH parameters and esophageal impedance of GERD patients. Methods: This study evaluated sex-based pathogenesis differences by comparing reflux episodes, mean nocturnal baseline impedance (MNBI) values, and post-reflux swallow-induced peristaltic wave (PSPW) index values of males with GERD and females with GERD using 24-h multichannel intraluminal impedance and pH monitoring. Results: We analyzed 181 patients (102 males and 79 females) with GERD. Reflux symptom index (RSI) scores were higher in females than that in males (P < 0.05). Males had significantly longer acid exposure times, higher DeMeester scores, and more acid reflux episodes than females (P < 0.05). Females had more instances of weakly acidic reflux than males (P < 0.01). The PSPW index values of males and females were similar (P > 0.05). Compared with females, males had lower MNBI values for the mid and distal esophagus (P < 0.05). However, with increasing age, the MNBI values of females decreased more rapidly than those of males. MNBI values of elderly patients of both sexes older than 60 years were similar. Conclusions: Acid reflux is more likely to occur in males; however, females tend to have more instances of weakly acid reflux. The integrity of the esophageal mucosa is more fragile in males than in females; however, the esophageal mucosal barrier attenuates more rapidly with increasing age in females than in males.

Critical appraisal of Rome IV criteria: hypersensitive esophagus does belong to gastroesophageal reflux disease spectrum.

The Rome IV Committee introduced a major change in the classification of functional gastrointestinal disorders, proposing a more restrictive definition of gastroesophageal reflux disease (GERD). It was suggested that hypersensitive esophagus (HE) may sit more firmly within the functional realm. It was suggested that GERD diagnosis should be based upon abnormal acid exposure time (AET) only, implying no advantage of impedance-pH over pH monitoring. Symptom association probability (SAP), symptom index (SI) and heartburn relief with proton pump inhibitor (PPI) therapy were regarded as unreliable, whereas a lack of response to PPI was considered as evidence of functional heartburn. These assumptions are contradicted by numerous studies showing the clinical relevance of weakly acidic refluxes and the diagnostic utility of SAP, SI and new impedance parameters, namely the post-reflux swallow-induced peristaltic wave (PSPW) index and the mean nocturnal baseline impedance (MNBI). The PSPW index and MNBI provide significant diagnostic advantage, particularly in patients with normal AET who can be classified as HE when both parameters are abnormal, even though SAP and SI are negative. Visceral pain modulators are recommended by the Rome IV Committee despite scanty evidence of efficacy, but a positive outcome with medical or surgical anti-reflux treatment has been reported by several studies of HE patients. Therefore, we believe that patients with endoscopy-negative heartburn should be investigated by means of impedance-pH monitoring with analysis of PSPW index and MNBI: such an approach provides accurate identification of HE cases, who remain, in our opinion, within the realm of GERD and should be treated accordingly.