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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., (© 2024 John Wiley & Sons Ltd.)

Introduction: Proton pump inhibitors (PPIs) have revolutionized the management of acid-related disorders, representing today the mainstay treatment of these conditions. However, despite their large range of indications and usefulness, the remarkable expansion of their use in the last two decades cannot be explained by the increasing prevalence of acid-related diseases only. An inappropriate prescription for clinical conditions in which the pathogenetic role of acid has not been documented has been described, with the natural consequence of increasing the costs and the potential risk of iatrogenic harm due to adverse events and complications recently emerged., Areas Covered: In this review, we summarize current indications of PPIs administration, potential adverse events associated with their chronic utilization, and misuse of PPIs. Moreover, we describe existing and possible initiatives for improving the use of PPIs, and some proposals for the future., Expert Opinion: PPI deprescribing is the preferred and most effective approach to reduce the use of PPIs, rather than adopting sharp discontinuation, probably due to fewer withdrawal symptoms. Nonetheless, large knowledge gaps still exist in clinical practice regarding the optimal approach of PPI deprescribing in various clinical scenarios. Further prospective well-designed international studies are eagerly warranted to improve our perspectives on controlling global PPI inappropriate use.

Introduction: The clinical management of chronic cough patients is challenging, and their response to proton pump inhibitors (PPIs) is considered as unsatisfactory. Few data concerning the association between impedance-pH variables and PPI response in these patients are available. Mean nocturnal baseline impedance (MNBI) and postreflux swallow-induced peristaltic wave (PSPW) index increase the diagnostic yield of impedance-pH in gastroesophageal reflux disease., Methods: Demographic, clinical, and endoscopy findings; impedance-pH; and high-resolution manometry tracings from consecutive patients assessed for cough were evaluated. Univariable and multivariable regression models were generated to evaluate the association between impedance-pH and high-resolution manometry findings, endoscopic and clinical characteristics, and PPI response., Results: A total of 178 patients were included. Eighty-four of 178 cough patients (47.2%) displayed grade C-D erosive esophagitis or were characterized by a pathological acid exposure time (AET) and/or positive symptom association probability/symptom index. When also considering MNBI and PSPW, 135 of 178 patients (75.8%) were characterized by the evidence of reflux disease (P < 0.001). Eighty patients (44.9%) had cough responding to PPIs, whereas 98 (55.1%) were nonresponders (P = 0.071). At the receiver operating characteristic analysis, both PSPW index and MNBI were associated to PPI responsiveness. MNBI and PSPW index showed higher sensitivity in predicting PPI response compared with AET and symptom association probability/symptom index. The area under the curves of MNBI and PSPW index were significantly higher than that of AET (P < 0.01 for both comparisons). When patients were stratified according to AET and excluding those with erosive esophagitis, pathological MNBI or PSPW index, hiatal hernia, and hypomotility features were associated to PPI response in all groups., Discussion: Our results demonstrate the usefulness of an up-front esophageal testing in discriminating reflux-related cough patients and predicting PPI response., (Copyright © 2021 by The American College of Gastroenterology.)

Background: The Lyon Consensus delineates impedance-pH parameters that can demonstrate/exclude gastro-oesophageal reflux disease (GERD). In patients with acid exposure time between 4% and 6%, GERD diagnosis has been considered inconclusive. In these cases, mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave (PSPW) index may either confirm or refute GERD diagnosis and represent predictors of proton pump inhibitor (PPI) response., Aims: To investigate the diagnostic yield of MNBI and PSPW index and their relationship with PPI response in patients with inconclusive GERD diagnosis., Methods: Review of impedance-pH tracings from PPI responder/non-responder patients with typical reflux symptoms. Multivariate regression analysis was performed to determine the association of MNBI and PSPW index to PPI response., Results: Among 233 patients evaluated, 145/233 (62.2%) were PPI responders; 62 had conclusive and 65 inconclusive evidence of GERD, 46 had reflux hypersensitivity, and 60 functional heartburn. Abnormal MNBI and PSPW index were significantly more frequent in inconclusive GERD as compared to the functional heartburn group (P < 0.001). Within the inconclusive GERD group, 35/65 (54%) patients were PPI responders and displayed a significantly higher proportion of cases with pathological MNBI or PSPW index as compared to non-responders (32/35 [91.4%] and 30/35 [85.7%] vs 9/30 [30%] and 7/30 [23.3%], P < 0.001). By multivariate analysis, pathological PSPW index and/or MNBI values were significantly associated with PPI response in all groups., Conclusions: The present study highlights the value of MNBI and PSPW index as adjunctive metrics in characterising patients with inconclusive evidence of GERD and identifying those responsive to PPI treatment., (© 2021 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background: The real size of the gastro-oesophageal reflux disease (GERD) population not responding to proton pump inhibitor (PPI) therapy has still not been fully elucidated. Causes of PPI refractoriness include incorrect diagnosis and lack of adherence to therapy, in terms of incorrect dosage and timing., Aims: To evaluate the prevalence of refractoriness to optimal PPI therapy and the contribution of non-erosive reflux disease (NERD), reflux hypersensitivity, and functional heartburn, to PPI refractoriness. The association of functional GI symptoms in non-responders was evaluated., Methods: Frequency and severity of GERD symptoms (heartburn, regurgitation, chest pain), dysphagia, belching, epigastric pain, postprandial distress, irritable bowel syndrome (IBS), globus, and ear nose and throat (ENT) symptoms were evaluated in patients previously classified as non-responders. Patients with at least one of the oesophageal symptoms with a frequency ≥3 /week were treated with esomeprazole 40 mg once daily for 8 weeks and then re-evaluated. Non-responders (patients with oesophageal symptoms ≥3 times per week) underwent 24 hour multichannel intraluminal impedance-pH monitoring., Results: Of 573 consecutive patients, 92 with oesophageal symptoms and classified as PPI-refractory underwent the esomeprazole trial; 60 did not respond. IBS, epigastric pain, and post-prandial distress episodes were associated with a poor response on multivariate analysis. NERD, reflux hypersensitivity, and functional heartburn patients constituted 32%, 42%, and 26%, respectively of the PPI-refractory group., Conclusions: True refractoriness in patients with GERD symptoms attending a secondary care setting is lower than previously reported. Following a careful history and optimal PPI dosing, the rate of refractoriness was 20%. True NERD constitutes only a third of the PPI-refractory group., (© 2018 John Wiley & Sons Ltd.)

Goals: The present study was aimed at evaluating, in dysphagic patients, the role of high-resolution manometry (HRM) findings, presence of gastroesophageal reflux disease (GERD), and proton-pump inhibitor (PPI) therapy on dysphagia perception., Background: A relevant proportion of patients with nonobstructive dysphagia present normal esophageal HRM findings. Patients with GERD often complain of dysphagia and factors, such as hypersensitivity, might be involved in its occurrence., Study: In total, 37 nonerosive reflux disease (NERD) patients with only dysphagia (group 1) and 52 patients with both dysphagia and typical GERD symptoms (group 2) were evaluated with symptom scores, HRM combined with impedance and 24 hours impedance-pH monitoring. In total, 44 NERD patients, not presenting dysphagia, underwent the same protocol. A total of 22/37 group 1 patients [11 with pathologic acid exposure time (AET)] were treated with esomeprazole 40 mg oid for 4 weeks and were reassessed during the last week of therapy., Results: A total of 15/37 group 1 patients (40%), 27/52 group 2 patients (52%), and 19/44 (43%) NERD patients presented pathologic AET [P=not significant (NS)]. Group 1 patients with a pathologic AET showed a significantly lower mean distal contractile integral (DCI) and a significant correlation (ρ=-0.71) between individual DCI and total bolus transit time values. During PPI therapy, in group 1 patients with pathologic AET, the mean dysphagia score value decreased significantly [7.5 (range, 3 to 9) before, 4 (range, 2 to 6) during PPI; P<0.01)] and mean DCI value increased significantly., Conclusions: In total, 40% of dysphagic patients show a pathologic AET and reduced peristaltic vigor. In these patients, an adequate PPI therapy significantly decreases dysphagia frequency and severity and improves the esophageal peristaltic force.

Background: Gastro-oesophageal reflux disease (GERD) may contribute to the onset of chronic cough (CC); however, the multichannel intraluminal impedance-pH (MII-pH) monitoring is often within the normal range and the response to proton pump inhibitors (PPIs) unsatisfactory. The measure of impedance baseline (IB) increases the sensitivity of MII-pH in patients with typical symptoms., Aim: To evaluate the role of MII-pH variables, including IB, in predicting PPI response and to define the characteristics of the reflux pattern in CC patients., Methods: Prospectively selected CC patients suspected GERD-related underwent MII-pH monitoring and, therefore, received a double dose of PPIs for at least 6 weeks. Patients filled symptom scores before MII-pH and after PPI therapy. MII-pH data were compared with those obtained in 60 non-erosive reflux disease patients with typical symptoms., Results: A total of 156 CC patients entered the study: 68 (43.5%) responders and 88 (56.5%) nonresponders to PPIs. The number of reflux episodes was significantly higher in CC compared with that in typical symptoms patients. Nonresponder CC patients with a pathological acid exposure time (AET) and/or IB value were 43/88 (49%), while 15/88 (17%) presented only pathological AET (P < 0.001). CC patients with a pathological AET or IB, or with both a pathological AET and IB, showed a probability of PPI response twofold greater than patients with normal AET and IB., Conclusions: The presence of a pathological AET or pathological IB in CC patients is associated with a greater probability of PPI response. IB is a promising variable in patients with CC, as it increases the diagnostic yield of MII-pH and allows confirmation of the GERD diagnosis in these patients., (© 2014 John Wiley & Sons Ltd.)

Gastro-esophageal reflux disease (GERD) is one of the most prevalent chronic diseases. Although proton pump inhibitors (PPIs) represent the mainstay of treatment both for healing erosive esophagitis and for symptom relief, several studies have shown that up to 40% of GERD patients reported either partial or complete lack of response of their symptoms to a standard PPI dose once daily. Several mechanisms have been proposed as involved in PPIs resistance, including ineffective control of gastric acid secretion, esophageal hypersensitivity, ultrastructural and functional changes in the esophageal epithelium. The diagnostic evaluation of a refractory GERD patients should include an accurate clinical evaluation, upper endoscopy, esophageal manometry and ambulatory pH-impedance monitoring, which allows to discriminate non-erosive reflux disease patients from those presenting esophageal hypersensitivity or functional heartburn. Treatment has been primarily based on doubling the PPI dose or switching to another PPI. Patients with proven disease, not responding to PPI twice daily, are eligible for anti-reflux surgery.

Background: It was recently shown that GERD patients have lower impedance baseline (IB) values than healthy controls and, that the esophageal acid exposure time (AET) correlates with IB levels., Goals: To explore the sensitivity of IB measurements in NERD patients, responders and non-responders to PPIs, when compared with pH-impedance (MII-pH) variables, and to evaluate whether this variable could represent a marker of GERD symptoms. Reproducibility and inter-observer agreement of IB measurement were also assessed. Study. MII-pH tracings from 44 NERD responders and 22 non-responders were analysed. Ten healthy volunteers underwent the same protocol. IB values were measured at the distal and proximal esophagus. IB was also analysed in a subgroup of patients and in controls with two methods and by two blinded operators., Results: Mean IB values at the distal esophagus were significantly lower in NERD patients than in controls. IB values did not differ between responders and non-responders. Of the 8 responders with negative AET and symptom association probability (SAP), 3 (37.5%) showed IB values lower than controls. IB values in responders with positive and negative SAP were similar (1832 (1596-2068) Ω vs 1667 (1361-1973) Ω, p: n.s.). No differences were found between the IB values measured with the two methods and the inter-observer agreement was good., Conclusions: IB is a promising and easy to calculate MII-pH variable and appears to increase the sensitivity of MII-pH monitoring. IB values cannot predict PPI response and are not associated with reflux perception in NERD patients.

Background: The unsatisfactory response to medical treatment in non-erosive patients is becoming a real challenge for gastroenterologists. Non-responder patients, evaluated under treatment, present symptoms which are related to non-acidic, mixed and proximal reflux episodes., Methods: To elucidate the reflux pattern and mechanisms related to persistence of symptoms despite treatment, oesophageal pH-impedance was performed in 55 non-erosive responder and 24 non-responder patients, studied off therapy. Ten responder and 10 non-responder patients underwent a repeated study during proton pump inhibitor treatment., Results: Non-responders were characterised by a higher overall number and larger proportion of symptomatic reflux episodes. Non-responders were also characterised by an enhanced sensitivity to acidic, mixed and proximal refluxes. Weakly acidic reflux accounted for 29% of symptomatic refluxes in non-responders and 34% in responders. Proportions of acidic and weakly acidic reflux episodes were comparable both in responders and non-responders when analysed off and on treatment., Conclusions: An increased overall number of reflux episodes and enhanced sensitivity to reflux are strongly associated with treatment failure. Treatment strategies aimed at decreasing transient lower oesophageal sphincter relaxations, pain modulators or anti-reflux surgery should be considered in non-responders in whom a significant relationship between symptoms and reflux has been confirmed., (Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background Non-erosive reflux disease ( NERD) patients are more sensitive than erosive esophagitis patients to weakly acidic reflux and to the presence of gas in the refluxate. Intra-esophageal acid perfusion sensitizes esophageal receptors to mechanical and chemical stimuli. Methods To establish whether acid sensitization plays a role in the perception of weakly acidic and mixed reflux episodes, 29 NERD patients, responders and 14 non-responders to proton pump inhibitors ( PPIs), underwent pH-impedance monitoring. Non-responders repeated the study while on PPIs. To assess the effect of acid exposure on symptom perception, the time period with pH below 4 was measured in 15- and 30-minute time-windows preceding the onset of each reflux episode. Key Results Considering weakly acidic and mixed refluxes, both in responder and non-responder patients (off PPIs), the symptomatic refluxes were preceded by a significantly higher cumulative acid exposure than the asymptomatic refluxes. In all patients, following acid reflux, the percentage of symptomatic weakly acidic reflux episodes was significantly higher than that of asymptomatic refluxes. Non-responder patients, off-treatment, were characterized by a lower proportion of weakly acidic reflux and mixed reflux episodes. In the non-responder patients on PPI, only mixed and weakly symptomatic reflux episodes were preceded by a higher cumulative acid exposure. Conclusions & Inferences In NERD patients, spontaneous acid reflux enhances subsequent reflux perception, regardless of acidity or liquid/mixed composition of episodes; in non-responder patients on PPIs, only the perception of mixed and weakly acidic reflux episodes seems to be mediated by a preceding acid exposure. [ABSTRACT FROM AUTHOR]

The article discusses a study of the diagnostic accuracy of acid exposure (AE) measurement at proximal esophagus (PE) in non-erosive reflux disease (NERD) patients. The authors recruited 93 NERD patients with typical symptoms responsive to proton pump inhibitor treatment to undergo esophageal manometry and multi-channel 24-hour pH-monitoring. They found that the measurement of distal AE improves the diagnostic yield as well as symptom-reflux correlation in erosive esophagitis but not in NERD patients.

Background Proximal acid reflux is common in gastro-oesophageal reflux disease and is a determinant of symptoms. Patients with hiatal hernia complain of more symptoms than those without and are less responsive to proton-pump inhibitors. Aim To evaluate the role of hiatal hernia on spatiotemporal characteristics of acid reflux. Methods Thirty seven consecutive gastro-oesophageal reflux disease patients underwent endoscopy, videofluoroscopy, manometry and multichannel 24-h pH test. Data were compared with those of 15 asymptomatic controls. Multivariate linear regression was used for statistical analysis. Results At videofluoroscopy, hiatal hernia was found in 16 of 37 patients. The mean size of hiatal hernia was 3.4 cm. Patients showed significantly prolonged acid clearance time, both at proximal and distal oesophagus, compared with controls. Hiatal hernia patients showed a significantly delayed acid clearance, along the oesophageal body, compared with non-hiatal hernia patients. The prolonged acid exposure was maintained during upright and supine position. The presence of hiatal hernia significantly predicted acid clearance delay in the distal and proximal oesophagus [at 10 cm below upper oesophageal sphincter: Δ + 2.5 min (95% confidence interval: 0.4–4.5); P < 0.02]. Conclusions The presence of hiatal hernia is a strong predictor of more prolonged proximal oesophageal acid exposure and clearance. Hiatal hernia is likely to play a role in the pathophysiology of gastro-oesophageal reflux disease symptoms, and should be taken into greater consideration in the treatment strategies of the disease. [ABSTRACT FROM AUTHOR]