Diagnosis of supra‐esophageal gastric reflux: correlation of oropharyngeal pH with esophageal impedance monitoring for gastro‐esophageal reflux

Background Oropharyngeal (OP) pH monitoring has been developed as a new way to diagnose supra‐esophageal gastric reflux (SEGR), but has not been well validated. Our aim was to determine the correlation between OP pH and gastro‐esophageal reflux (GER) events detected by multichannel intraluminal impedance‐pH (MII‐pH). Methods Fifteen patients (11 males, median age 10.8 years) with suspected GER were prospectively evaluated with ambulatory 24‐h OP pH monitoring (positioned at the level of the uvula) and concomitant esophageal MII‐pH monitoring. Potential OP events were identified by the conventional pH threshold of <4 and by the following alternative criteria: (i) relative pH drop >10% from 15‐min baseline and (ii) absolute pH drop below thresholds of <5.5, 5.0, and 4.5. The 2‐min window preceding each OP event was analyzed for correlation with an episode of GER detected by MII‐pH. Key Results A total of 926 GER events were detected by MII‐pH. Application of alternative pH criteria increased the identification of potential OP pH events; however, a higher proportion of OP events had no temporal correlation with GER (45–81%), compared with the conventional definition of pH < 4 (40%). A total of 306 full‐column acid reflux episodes were detected by MII‐pH, of which 10 (3.3%) were also identified by OP pH monitoring. Conclusions & Inferences Use of extended pH criteria increased the detection of potential SEGR events, but the majority of decreases in OP pH were not temporally correlated with GER. Oropharyngeal pH monitoring without concurrent esophageal measurements may overestimate the presence of SEGR in children.     

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.     

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.     

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.     

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.     

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.