The frequency of apneas in very preterm infants is increased after non‐acid gastro‐esophageal reflux

Background To evaluate whether physical and/or chemical features of gastro‐esophageal reflux (GER) influence its relationship with apnea of prematurity (AOP). Methods Fifty‐eight preterm newborns (GA ≤33 weeks) with recurrent apneas were studied by simultaneous polysomnography and combined impedance and pH monitoring, to analyze whether the correlation between GER and AOP varies according to the acidity, duration and height of GERs. Key Results The frequency of apnea (number apnea/min) occurring after‐GER [median (range) 0.07 (0–0.25)] was higher than the one detected in GER‐free period [0.06 (0.04–0.13), P = 0.015], and also than the one detected before‐GER [0 (0–0.8), P = 0.000]. The frequency of apneas detected in the 30’’ after pH‐GER [median (range), 0 min^?1 (0–1.09)] was higher than the frequency detected in the 30’’ before [0 (0–0.91), P = 0.04]; even more, the frequency of apneas detected after non‐acid MII‐GER episodes [0 (0–2)] was significantly higher than the one detected before [0 (0–1), P = 0.000], whereas the frequency of apneas detected before acid MII‐GER episodes [0 (0–0.67)] did not differ from the one detected after [0 (0–2), P = 0.137]. The frequency of pathological apneas detected in the 30’’ after‐GER (0 min^?1, range 0–0.55) was higher than the frequency detected before (0, range 0–0.09; P = 0.001). No difference in mean height or in mean duration was found between GERs correlated and those non‐correlated to apnea. Conclusions & Inferences Non‐acid GER is responsible for a variable amount of AOP detected after‐GER: this novel finding must be taken into consideration when a therapeutic strategy for this common problem is planned.     

Effect of low‐proof alcoholic beverages on duodenogastro‐esophageal reflux in health and GERD

Background Alcoholic beverages are known to increase acidic gastro‐esophageal reflux (GER) and the risk of esophagitis. Moreover, duodenogastro‐esophageal reflux (DGER), containing bile acids, was shown to harmfully alter the esophageal mucosa, alone and synergistically with HCl and pepsin. However, studies directly addressing potential effects of different low proof alcoholic beverages on DGER in health and disease are missing. Methods Bilitec readings for beer and white, rose, and red wine were obtained in vitro from pure and from mixtures with bile. One‐hour DGER monitoring and pH‐metry were performed in 12 healthy subjects and nine reflux patients with DGER after ingestion of a standardized liquid meal together with 300 mL of water, white wine, and in the volunteers, beer and rose wine. Key Results Bilitec measurement was found to be feasible in the presence of beer, white wine, and using a threshold of 0.25, rose wine. However, the presence of red wine resulted in extinction values above this threshold. The consumption of all investigated alcoholic beverages, especially of white wine, triggered increased acidic GER, both in healthy participants and patients with reflux disease. In contrast, no relevant DGER was found after intake of alcoholic beverages. Conclusions & Inferences Fiber‐optic bilirubin monitoring can be used for DGER monitoring in combination with alcoholic beverages, except with red wine. Low‐proof alcoholic beverages are a strong trigger of GER, but not of DGER, both in healthy subjects and patients with reflux disease.     

Increase of weakly acidic gas esophagopharyngeal reflux (EPR) and swallowing‐induced acidic/weakly acidic EPR in patients with chronic cough responding to proton pump inhibitors

Background Gastro‐esophageal reflux disease (GERD)‐related chronic cough (CC) may have multifactorial causes. To clarify the characteristics of esophagopharyngeal reflux (EPR) events in CC patients whose cough was apparently influenced by gastro‐esophageal reflux (GER), we studied patients with CC clearly responding to full‐dose proton pump inhibitor (PPI) therapy (CC patients). Methods Ten CC patients, 10 GERD patients, and 10 healthy controls underwent 24‐h ambulatory pharyngo‐esophageal impedance and pH monitoring. Weakly acidic reflux was defined as a decrease of pH by >1 unit with a nadir pH >4. In six CC patients, monitoring was repeated after 8 weeks of PPI therapy. The number of each EPR event and the symptom association probability (SAP) were calculated. Symptoms were evaluated by a validated GERD symptom questionnaire. Key Results Weakly acidic gas EPR and swallowing‐induced acidic/weakly acidic EPR only occurred in CC patients, and the numbers of such events was significantly higher in the CC group than in the other two groups (P < 0.05, respectively). Symptom association probability analysis revealed a positive association between GER and cough in three CC patients. Proton pump inhibitor therapy abolished swallowing‐induced acidic/weakly acidic EPR, reduced weakly acidic gas EPR, and improved symptoms (all P < 0.05). Conclusions & Inferences Most patients with CC responding to PPI therapy had weakly acidic gas EPR and swallowing‐induced acidic/weakly acidic EPR. A direct effect of acidic mist or liquid refluxing into the pharynx may contribute to chronic cough, while cough may also arise indirectly from reflux via a vago‐vagal reflex in some patients.     

High‐resolution esophageal pressure topography is superior to conventional sleeve manometry for the detection of transient lower esophageal sphincter relaxations associated with a reflux event

Background Transient lower esophageal sphincter relaxations (TLESRs) are the main mechanism underlying gastro‐esophageal reflux and are detected during manometric studies using well defined criteria. Recently, high‐resolution esophageal pressure topography (HREPT) has been introduced and is now considered as the new standard to study esophageal and lower esophageal sphincter (LES) function. In this study we performed a head‐to‐head comparison between HREPT and conventional sleeve manometry for the detection of TLESRs. Methods A setup with two synchronized MMS‐solar systems was used. A solid state HREPT catheter, a water‐perfused sleeve catheter, and a multi intraluminal impedance pH (MII‐pH) catheter were introduced in 10 healthy volunteers (M6F4, age 19–56). Subjects were studied 0.5 h before and 3 h after ingestion of a standardized meal. Tracings were blinded and analyzed by the three authors according to the TLESR criteria. Key Results In the HREPT mode 156 TLESRs were scored, vs 143 during sleeve manometry (P = 0.10). Hundred and twenty‐three TLESRs were scored by both techniques. Of all TLESRs (177), 138 were associated with reflux (78%). High‐resolution esophageal pressure topography detected significantly more TLESRs associated with a reflux event (132 vs 119, P = 0.015) resulting in a sensitivity for detection of TLESRs with reflux of 96% compared to 86% respectively. Analysis of the discordant TLESRs associated with reflux showed that TLESRs were missed by sleeve manometry due to low basal LES pressure (N = 5), unstable pharyngeal signal (N = 4), and residual sleeve pressure >2 mmHg (N = 10). Conclusions & Inferences The HREPT is superior to sleeve manometry for the detection of TLESRs associated with reflux. However, rigid HREPT criteria are awaited.     

Reflux monitoring in children

Recently, multichannel intraluminal impedance (MII) monitoring was added to the repertoire of tests to evaluate the (patho)physiology of gastroesophageal reflux (GER) in children. Its advantage above the sole monitoring of the esophageal pH lies in the ability of the detection of both acid and nonacid GER and to discern between liquid and gas GER. Currently, combined 24 h pH‐MII monitoring is recommended for evaluation of gastro‐esophageal reflux disease (GERD) and its relation to symptoms in infants and children, despite the lack of reference values in these age groups. There is new evidence in the current issue of this Journal supporting the role of pH‐MII monitoring for the evaluation of children presenting with gastrointestinal symptoms suggestive of GERD and the prediction of the presence of reflux esophagitis. However, several issues should be taken into account when performing pH‐MII clinically.     

Increased TRPV1 gene expression in esophageal mucosa of patients with non‐erosive and erosive reflux disease

Background Transient receptor potential channel vanilloid subfamily member‐1 (TRPV1) may play a role in esophageal perception. TRPV1 mRNA and protein expression were examined in the esophageal mucosa of non‐erosive reflux disease (NERD) and erosive esophagitis (EE) patients and correlated to esophageal acid exposure. Methods Seventeen NERD patients, eight EE patients and 10 healthy subjects underwent endoscopy after a 3‐week washout from proton pump inhibitors or H2 antagonists. Biopsies, obtained from the distal esophagus, were used for conventional histology, for Western blot analysis and/or quantitative real‐time polymerase chain reaction (qPCR). Overall 13 NERD patients, four EE patients and five controls underwent ambulatory pH‐testing. Key Results TRPV1 expression was increased in all NERD and EE patients, as measured by Western blot analysis (0.65 ± 0.07 and 0.8 ± 0.05 VS 0.34 ± 0.04 in controls; P < 0.01) and by qPCR (1.98 ± 0.21 and 2.52 ± 0.46 VS 1.00 ± 0.06; P < 0.01). Neutrophilic infiltration, in the mucosa, was detected only in EE patients. Conclusions & Inferences Non‐erosive reflux disease and EE patients presented increased TRPV1 receptors mRNA and protein, although no correlation with acid exposure was demonstrated. Increased TRPV1 in the esophageal mucosa may contribute to symptoms both in NERD and EE patients and possibly account for peripheral mechanisms responsible for esophageal hypersensitivity in NERD patients.     

Mechanism of gastroesophageal reflux in patients with obstructive sleep apnea syndrome

Background It has been reported that the prevalence of gastroesophageal reflux (GER) disease is high in patients with obstructive sleep apnea (OSA). End‐inspiratory intra‐esophageal pressure decreases progressively during OSA, which has been thought to facilitate GER in OSA patients. The aim of our study was to clarify the mechanisms of GER during sleep (sleep‐GER) in OSA patients. Methods Eight OSA patients with reflux esophagitis (RE), nine OSA patients without RE, and eight healthy controls were studied. Polysomnography with concurrent esophageal manometry and pH recording were performed. Key Results Significantly more sleep‐GER occurred in OSA patients with RE than without RE or in controls (P < 0.05). The severity of OSA did not differ between OSA patients with RE and without RE. Sleep‐GER was mainly caused by transient lower esophageal sphincter relaxation (TLESR), but not by negative intra‐esophageal pressure during OSA. During OSA gastroesophageal junction pressure progressively increased synchronous to intra‐esophageal pressure decrease. OSA patients had significantly more TLESR events during sleep related to preceding arousals and shallow sleep, but the number of TLESR events was not related to RE. Conclusions & Inferences In OSA patients, sleep‐GER was mainly caused by TLESR, but not by negative intra‐esophageal pressure due to OSA.     

Failure to respond to physiologic challenge characterizes esophageal motility in erosive gastro‐esophageal reflux disease

Background Non‐specific esophageal dysmotility with impaired clearance is often present in patients with gastro‐esophageal reflux disease (GERD), especially those with erosive disease; however the physio‐mechanic basis of esophageal dysfunction is not well defined. Methods Retrospective assessment of patients with erosive reflux disease (ERD; n = 20) and endoscopy negative reflux disease (ENRD; n = 20) with pathologic acid exposure on pH studies (>4.2% time/24 h) and also healthy controls (n = 20) studied by high resolution manometry. Esophageal motility in response to liquid and solid bolus swallows and multiple water swallows (MWS) was analyzed. Peristaltic dysfunction was defined as failed peristalsis, spasm, weak or poorly coordinated esophageal contraction (>3 cm break in 30 mmHg isocontour). Key Results Peristaltic dysfunction was present in 33% of water swallows in controls, 56% ENRD and 76% ERD respectively (P < 0.023 vs controls, P = 0.185 vs ENRD). The proportion of effective peristaltic contractions improved with solid compared to liquid bolus in controls (18%vs 33%, P = 0.082) and ENRD (22%vs 54%, P = 0.046) but not ERD (62%vs 76%, P = 0.438). Similarly, MWS was followed by effective peristalsis in 83% of controls and 70% ENRD but only 30% ERD patients (P < 0.017 vs controls and P < 0.031 vs ENRD). The association between acid exposure and dysmotility was closer for solid than liquid swallows (r = 0.52 vs 0.27). Conclusions & Inferences Peristaltic dysfunction is common in GERD. ERD patients are characterized by a failure to respond to the physiologic challenge of solid bolus and MWS that is likely also to impair clearance following reflux events and increase exposure to gastric refluxate.     

Cardiovascular compression of the esophagus and spread of gastro‐esophageal reflux

Background Factors that determine the spread of gastro‐esophageal reflux (GER) along the length of the esophagus are not known. We investigated if cardiovascular (CV) compressions on the esophagus may determine the spread of refluxate into the proximal esophagus. Methods High‐resolution manometry (HRM) and multi‐channel intra‐luminal impedance recording (MIIR) were performed simultaneously in 10 normal subjects in the recumbent and upright positions. Pulsatile pressure increases on the esophagus (marker of CV compression) were identified on the HRM. Spread of refluxate into the esophagus was determined by the MIIR. Key Results Cardiovascular compression zones were observed in the esophagus in 9 out of 10 subjects in recumbent position. Forty percent of GER episodes were limited to the distal esophagus in the recumbent position and CV compression pressure was greater than distal esophageal pressure at the time of GER in all such cases. On the other hand, distal esophageal pressure was greater than CV compression pressure when the refluxate extended into the proximal esophagus. In the upright position, CV compression was less frequent than recumbent position and only 12% of GER episodes were limited to the distal esophagus. Conclusions & Inferences Cardiovascular compression of the esophagus is frequently observed in normal healthy subject and restricts the spread of refluxate into the proximal esophagus.     

Relationship between reflux diseases and obstructive sleep apnea together with continuous positive airway pressure treatment efficiency analysis

BackgroundObstructive sleep apnea (OSA) is known to be highly associated with reflux diseases. There is evidence that continuous positive airway pressure (CPAP) can decrease the clinical symptoms of gastroesophageal reflux (GER) in OSA patients, but whether CPAP can decrease nocturnal laryngopharyngeal reflux (LPR) episodes is still lack of strong evidence.ObjectiveTo investigate the efficiency of CPAP on LPR and the relationship between LPR, GER and OSA.Study designretrospective study.MethodsForty adult patients who had confirmed OSA by polysomnography and suspected LPR were enrolled. Their results of synchronous polysomnography and 24 h esophageal and oropharyngeal Dx-pH monitoring were analyzed. Twenty-seven OSA patients were treated with CPAP on the second night. The nocturnal reflux parameters with and without CPAP treatment were compared.Results15.0% and 42.5% of OSA patients were associated with LPR and GER through Dx-pH monitoring respectively. Nevertheless, more than one reflux attack falling below pH6.0 of oropharynx during sleep time was detected in 80.0% patients. There was a significant inverse correlation between the lowest/mean pH values of oropharynx and obstructive apnea index (OAI), so was the lowest pH values of esophagus. Significant positive correlation was calculated between the total number of reflux episodes below pH6.0 of oropharynx and apnea–hypopnea index (AHI)/OAI/hypopnea index (HI). A similar positive correlation was also significant between AHI/OAI and GER parameters. The assessment of the efficacy of CPAP treatment showed significant difference both in GER and LPR related parameter.ConclusionsOSA patients have a higher incidence of nocturnal LPR and GER. CPAP treatment can effectively reduce both GER and LPR attacks while disordered sleep events reduced in OSA patients.     

Treatment of gastro‐esophageal reflux disease: the new kids to block

Refractory gastro‐esophageal reflux disease (GERD), defined as persistent symptoms despite proton pump inhibitor (PPI) therapy, is an increasingly prevalent condition and is becoming a major challenge for the clinician. Since non‐acidic reflux may be associated with symptoms persisting during PPI treatment, the lower esophageal sphincter (LES), the most important barrier protecting against reflux, has become an important target for the treatment of (refractory) GERD. Preclinical research has identified several receptors that are involved in the control of transient lower esophageal sphincter relaxations (TLESRs), the predominant mechanism of both acid and non‐acidic reflux events, and several drugs have now been tested in humans. The GABA_B agonist baclofen has demonstrated to effectively reduce the rate of TLESRs and the amount of reflux in both GERD patients and healthy volunteers. Nevertheless, the occurrence of central side effects limits its clinical use for the treatment of GERD. Several analogues are being developed to overcome this limitation and have shown promising results. Additionally, metabotropic glutamate receptor 5 (mGluR5) receptor antagonists have shown to reduce both acid and non‐acidic reflux in GERD patients and several molecules are currently being evaluated. Although CB₁ antagonists have been shown to reduce TLESRs, they are also associated with central side effects, limiting their clinical applicability. Despite the identification of several potentially interesting drugs, the main challenge for the future remains the reduction of central side effects. Moreover, future studies will need to demonstrate the efficacy of these treatments in patients with refractory GERD.     

The presence of pepsin in the lung and its relationship to pathologic gastro-esophageal reflux

Background Pepsin has been proposed as a biomarker of reflux‐related lung disease. The goal of this study was to determine (i) if there is a higher reflux burden as measured by pH‐MII in patients that are pepsin positive in the lung, and (ii) the sensitivity of pepsin in predicting pathologic reflux by pH, MII, and EGD. Methods We recruited children between the ages of 1–21 with chronic cough or asthma undergoing bronchoscopy, esophagogastroduodenoscopy (EGD), and multichannel intraluminal impedance (pH‐MII) probe placement. The reflux profiles were compared between those patients who were pepsin positive and negative; proportions were compared using Chi‐squared analyses and means were compared using t‐testing. Key Results Only the mean number of non‐acid reflux events was associated with pepsin positivity (0.04). The sensitivity and specificity of pepsin in predicting pathologic reflux by pH‐MII or EGD was 57% and 65%, respectively. The positive predictive value of pepsin in predicting pathologic reflux by pH, MII or EGD was 50% (11/22), and the negative predictive value was 71% (20/28). There was a significantly higher mean LLMI in patients who were pepsin positive compared with pepsin negative patients (81 ± 54 vs 47 ± 26, P = 0.001). Conclusions & Inferences Lung pepsin cannot predict pathologic reflux in the esophagus, but its correlation with lung inflammation suggests that pepsin may be an important biomarker for reflux‐related lung disease.     

Concomitant irritable bowel syndrome is associated with failure of step‐down on‐demand proton pump inhibitor treatment in patients with gastro‐esophageal reflux disease

Background The predictors for treatment failure of on‐demand proton pump inhibitor (PPI) therapy in gastro‐esophageal reflux disease (GERD) patients are unclear. We studied the efficacy and predictors for treatment failure of step‐down on‐demand PPI therapy in patients with non‐erosive reflux disease (NERD) and those with low grade erosive esophagitis. Methods Consecutive symptomatic GERD patients who had positive esophageal pH studies and complete symptom resolution with initial treatment of esomeprazole were given step‐down on‐demand esomeprazole for 26 weeks. Patients with esophagitis of Los Angeles (LA) grade C or above and recent use of PPI were excluded. Treatment failure was defined as an inadequate relief of reflux symptoms using global symptom assessment. Potential predictors of treatment failure were determined using multivariate analysis. Key Results One hundred and sixty three NERD and 102 esophagitis patients were studied. The 26‐week probability of treatment failure was 36.2% (95% CI: 23.9–46.5%) in NERD group and 20.1% (95% CI: 10.9–28.3%) in esophagitis group, respectively (P = 0.021). Irritable bowel syndrome (adjusted HR: 2.1, 95% CI: 1.5–3.8, P = 0.01), in addition to daily reflux symptom (adjusted hazard ratio: 2.7, 95% CI: 1.9–4.2, P = 0.001) and concomitant dyspepsia (adjusted hazard ratio: 1.7, 95% CI: 1.1–2.8, P = 0.04), were independent predictors for treatment failure. Conclusions & Inferences Compared to patients with esophagitis, NERD patients have higher failure rate of on‐demand PPI therapy. Concomitant irritable bowel syndrome, in addition to daily reflux symptom and dyspepsia, is associated with the failure of on‐demand PPI in these patients.     

Increasing body weight enhances prevalence and proximal extent of reflux in GERD patients ‘on’ and ‘off’ PPI therapy

Background Increased body weight is associated with higher intragastric pressure. Proximal extent of reflux is a determinant of symptoms in patients with gastro‐esophageal reflux disease (GERD). We aimed to investigate the association between body mass index (BMI) and abdominal circumference on the incidence and proximal extent of reflux. Methods A total of 95 patients [37 men, age 51(16–82) years] with typical and/or atypical GERD symptoms underwent 24 h impedance‐pH monitoring. Forty‐nine patients were studied ‘off’ and 46 ‘on’ proton pump inhibitors (PPI) treatment. Reflux was classified as acid (pH < 4) or weakly acidic (pH 4–7). Proximal extent was defined as the number of reflux events reaching ≥15 cm above the lower esophageal sphincter. Body mass index and abdominal circumference (cm) were assessed. Key Results In patients ‘off’ PPI, there was a correlation between BMI and esophageal acid exposure (ρ = 0.53, P < 0.001), volume exposure (ρ = 0.48, P < 0.001), total number of reflux events (ρ = 0.47, P < 0.001) and number of acid reflux events (ρ = 0.49, P < 0.001). In patients ‘on’ PPI there was a correlation between BMI and esophageal acid exposure (ρ = 0.32, P = 0.03), volume exposure (ρ = 0.46, P < 0.01) and total number of reflux events (ρ = 0.33, P = 0.03). Similar correlations were found between abdominal circumference and reflux. A correlation between BMI and proximal extent of reflux was present in patients ‘off’ PPI (ρ = 0.32, P = 0.03). In patients ‘on’ PPI, we found a correlation between abdominal circumference and proximal extent (ρ = 0.31, P = 0.03). Conclusions & Inferences Body mass index and abdominal circumference may contribute to GER and its proximal extent, in patients ‘on and ‘off’ PPI. Further studies investigating the role of weight reduction in the control of GERD symptoms are warranted.     

Riser’s reflux – an eye‐opening experience

Background Patients with gastro‐oesophageal reflux disease (GORD) commonly report waking up in the morning with a sour or bitter taste in their mouth. The aim of the study was to compare the prevalence and frequency of acid reflux events prior to and immediately after awakening from sleep in the morning between GORD patients and normal subjects. Methods Thirty‐nine patients with heartburn at least three times a week and abnormal pH test and nine healthy controls were included. All subjects were evaluated by demographic and GORD Symptom Checklist questionnaires. Subjects underwent pH testing concomitantly with actigraphy. A novel technology that simultaneously integrates raw actigraphy and pH monitoring data was utilized to determine the presence, frequency, and characteristics of acid reflux events prior to (up to 1 h) and immediately after (10 and 20 min) awakening from sleep in the morning. Key Results Nineteen (48.7%) of the GORD patients had an acid reflux event within the first 20 min after awakening from sleep in the morning as compared to only seven (17.9%) during the hour prior to awakening. Within the first 10 and 20 min after awakening, patients had a total of 32 and 60 acid reflux events, respectively, as compared to 14 during the 1 h prior to awakening (P < 0.05). None of the healthy control patients demonstrated any reflux events during these three studied periods (P < 0.001). Conclusions & Inferences Riser’s reflux is very common among GORD patients and possibly may explain reports of early‐morning GORD symptoms.     

Association between respiratory events and nocturnal gastroesophageal reflux events in patients with coexisting obstructive sleep apnea and gastroesophageal reflux disease

BackgroundLiterature has addressed the increased prevalence of gastroesophageal reflux disease (GERD) in obstructive sleep apnea (OSA). Significant improvement of GERD has been found after OSA treatment. However, precise mechanisms underlying this correlation remain unclear. We examined the association between nocturnal gastroesophageal reflux (GER) and sleep events in patients with coexisting OSA and GERD.MethodsA case-crossover study among 12 patients with coexisting moderate–severe OSA and GERD was conducted. Participants underwent simultaneous polysomnography and esophageal impedance and pH monitoring. GER subtypes (ie, acid reflux, non-acid reflux) were defined as outcomes. Respective control time points were selected in all eligible control periods. Each sleep event was assessed individually. Estimated odds ratios (ORs) and 95% confidence intervals (CIs) were analyzed. A p-value of < 0.05 was considered significant.ResultsPatients were determined as moderate to severe OSA (respiratory disturbance index of 42.66 [±22.09]). There were a total of 50 GER episodes, 22 acid reflux and 28 non-acid reflux. Arousals and awakenings were significantly associated with subsequent GER events. The OR for GER following an arousal was 2.31 (95% CI 1.39–3.68; p < 0.001) and following an awakening was 3.71 (95% CI 1.81–7.63; p < 0.001). GER events were significantly less likely to occur after other respiratory events (OR 0.38 [95% CI 0.18–0.82]; p = 0.01). No sleep events followed GER events (p > 0.05).ConclusionsBoth awakening and arousal appear to precipitate any subtype of GER events in patients with coexisting GERD and moderate to severe OSA. However, GER events were significantly less likely to occur after other respiratory events and did not appear to cause sleep-related events.     

Characteristics of gastro‐esophageal reflux episodes in Barrett’s esophagus,erosive esophagitis and healthy volunteers

Background Gastro‐esophageal reflux is considered a major culprit in the pathogenesis of Barrett’s esophagus (BE). Still, there is controversy on the role of weakly acidic and weakly alkaline reflux in BE. To compare characteristics of reflux episodes patients with BE, erosive esophagitis (EE), and healthy volunteers (HV). Methods One hundred consecutive patients with BE (75 short‐segment BE, 25 long‐segment BE), 50 with EE and 48 HV underwent multichannel intraluminal impedance‐pH off‐therapy. We quantified esophageal acid exposure, characteristics, and proximal extension of reflux episodes. Key Results Total and acid reflux episodes gradually increased from HV [28 (17.5–43) and 18 (8–31)] to EE [73.5 (54–96) and 52 (39–68)], short‐segment BE (SSBE) [83 (73.2–131) and 65 (43.3–95)] and long‐segment BE (LSBE) [105 (102–187) and 77 (75–107)]. Weakly acidic reflux episodes were significantly higher (P < 0.05) in LSBE [36 (27.5–50.5)] and SSBE [34 (18.5–41)] compared to EE [21.5 (15–37)] and HV [19 (14–25)]. No differences in terms of proportion of acid, weakly acidic and weakly alkaline reflux were found [HV (49%–49%–2%) vs EE (68%–32%–1%) vs SSBE (65%–34%–1%) vs LSBE (69%–30%–1%); P = ns]. In LSBE, a higher percentage of reflux episodes (P < 0.05) reached the proximal esophagus (59%) compared with SSBE (43%). Conclusions & Inferences Barrett esophagus patients have more severe reflux as shown by the number of acid and weakly acidic reflux episodes, re‐reflux episodes and proximal migration. Given that PPI change only the pH of the refluxate, the role of weakly acidic reflux in Barrett’s patients on acid suppressive therapy warrants further investigation.     

Measurement of acid exposure of proximal esophagus: a better tool for diagnosing non‐erosive reflux disease

Background The sensitivity of 24‐h pH monitoring is poor in non‐erosive reflux disease (NERD). In NERD patients, the proximal extent of acid reflux is one of the main determinants of reflux perception. The present study was aimed to compare the diagnostic accuracy of acid exposure time (AET), at 5 cm above the lower esophageal sphincter, with those at 10 cm and at 3 cm below the upper esophageal sphincter as well as the reproducibility of these parameters. Methods A total of 93 consecutive NERD patients, with typical symptoms responsive to proton pump inhibitor treatment, and 40 controls underwent esophageal manometry and multi‐channel 24‐h pH‐test; 13 patients underwent the same study on two occasions. Symptom association probability (SAP) values were evaluated at each esophageal level. Key Results The ROC curve indicates that the area under the curve was 0.79 at distal (SE = 0.039), 0.87 (SE = 0.032) at proximal (P = 0.029 vs distal), and 0.85 (SE = 0.033) at very proximal esophagus (P = 0.148). AET showed a reproducibility of 61% (Kappa 0.22) at distal esophagus, 77% (Kappa 0.45) at proximal and 53% (Kappa 0.05) at very proximal esophagus. The percentage of patients with a positive SAP was not significantly different when assessed at the distal compared with the proximal esophagus. Conclusions & Inferences In NERD patients, the diagnostic yield of the pH test is significantly improved by the assessment of AET at the proximal esophagus. As this variable seems to be less affected by the day to day variability, it could be considered a reliable and useful diagnostic tool in NERD patients.     

Gastroesophageal and laryngopharyngeal reflux profiles in patients with obstructive sleep apnea/hypopnea syndrome as determined by combined multichannel intraluminal impedance-pH monitoring

Background The profiles of gastroesophageal reflux (GER) and laryngopharyngeal reflux (LPR) in patients with obstructive sleep apnea/hypopnea syndrome (OSAHS) have never been explored. The aim of the study was to investigate the reflux profile in OSAHS patients. Methods Consecutive snoring out‐patients suspected with having OSAHS and 20 healthy volunteers were included. All subjects underwent simultaneous 24‐h combined multichannel intraluminal impedance–pH (MII–pH) monitoring and polysomnography. Obstructive sleep apnea/hypopnea syndrome was defined when the apnea/hypopnea index was over 5. Stepwise multiple logistic regression analysis was performed to determine the predictor for OSAHS. Key Results Fifty‐three patients were included, 37 with and 16 without OSAHS. The prevalence of reflux symptoms was similar between OSAHS (35.1%) and non‐OSHAS (37.5%) patients. More OSAHS patients, compared with non‐OSAHS patients and healthy volunteers, had pathologic acid GER, nocturnal acid GER, and prolonged acid clearance (P < 0.001). However, no difference in non‐acid reflux episodes was observed among the three groups. Laryngopharyngeal reflux was detected in 51.4%, 43.8%, and 35.0% of OSAHS, non‐OSAHS, and healthy volunteers, respectively (P = 0.034). In OSAHS patients, there was no difference in the sleep parameters between patients with and without LPR. Body mass index was the only predictor of OSAHS in the regression analysis. Conclusions & Inferences OSAHS patients have more pathologic acid GER and prolonged acid clearance than non‐OSAHS patients whereas non‐acid reflux was similar between the two groups. However, BMI, not GER, is the only independent predictor for OSAHS. Laryngopharyngeal reflux occurs in more than half of OSAHS patients despite no significant association with OSAHS.     

Decreased sympathetic inhibition in gastroesophageal reflux disease

This study was undertaken to evaluate autonomic nervous system function in patients with gastroesophageal reflux disease. Based on clinical criteria, 28 consecutive patients with no history of heart, metabolic, or neurologic disease (mean age 41 y, range 20–62 y) reporting with upper gastrointestinal symptoms typical of gastroesophageal reflux underwent esophageal manometry, ambulatory 24-hour pH study with electrocardiographic monitoring, power spectral analysis of heart rate variability, and cardiovascular tests. Twelve healthy subjects served as controls. A positive result of prolonged esophageal pH study (pH in the distal esophagus less than 4, lasting more than 4.2% of recording time) was observed in 21 patients (reflux group); seven patients were categorized in the nonreflux group. No patient showed arrhythmias or any correlation between heart rate variability changes during electrocardiographic monitoring and episodes of reflux (pH less than 4, lasting more than 5 minutes). A decrease of sympathetic function occurred only in the reflux group (p<0.05) supported by the lower increase of systolic/diastolic blood pressure at sustained handgrip. No other cardiovascular tests showed statistically significant differences in the control or nonreflux groups. Total time reflux showed an inverse correlation with sympathetic function in the reflux group (r=-0.415, p<0.028). We concluded that there is some evidence for a slightly decreased sympathetic function in patients with gastroesophaged reflux disease that is inversely correlated with total time reflux. In these patients, decreased sympathetic function may cause dysfunction of intrinsic inhibitory control with increased transient spontaneous lower-esophageal sphincter relaxations, thus resulting in gastroesophageal reflux disease.