Characteristics of nighttime reflux assessed using multichannel intraluminal impedance pH monitoring and a portable electroencephalograph

Gastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances. Although the mechanisms of this association have not been fully elucidated, nighttime reflux plays a central role. However, the detailed characteristics of nighttime reflux occurring during sleep are unknown. The aim of the present study was to examine the characteristics and prevalence of nighttime reflux in the natural sleep environment of GERD patients. Seventeen patients experiencing daily moderate‐to‐severe heartburn and/or regurgitation were studied using multichannel intraluminal impedance pH monitoring and electroencephalography off‐proton pump inhibitor treatment. Nighttime reflux was divided based on reflux type (liquid or gas), acidity (acidic, weakly acidic, or alkaline) and extent (distal only or proximal migration) according to the standard criteria. Nighttime phases were divided as follows: recumbent‐awake before falling asleep, nonrapid eye movement, rapid eye movement, awakening from sleep, and post‐awakening in the morning. Among 184 nighttime refluxes, 43 (23%) occurred during recumbent‐awake before falling asleep, 28 (15%) during nonrapid eye movement, 14 (8%) during rapid eye movement, 86 (46%) during awakening from sleep, and 13 (7%) during post‐awakening in the morning. Liquid reflux was more common in awakening during sleep (92%), nonrapid eye movement (100%), and rapid eye movement (100%) compared with awakening before falling asleep (68%). The prevalence of proximal migration was significantly lower in nonrapid eye movement and rapid eye movement than in the other phases. There were no differences in acidity and bolus clearance time among the phases. Thirteen (65%) of 20 events with GERD symptoms had nighttime reflux, suggesting that only 7.1% (13 of 184) of nighttime refluxes were symptomatic. Nighttime reflux was observed in 48 (11%) of 425 awakening episodes during sleep. Different reflux patterns at each phase during nighttime might explain the pathogenesis of GERD and its related sleep disturbances.     

Multichannel intraluminal impedance and pH monitoring in gastroesophageal reflux disease

The role of acid is very well established in the pathogenesis of gastroesophageal reflux disease and acid suppression constitutes the main approach to its medical treatment. With the current frequent use of proton pump inhibitors, we are seeing increasing numbers of patients in whom symptoms persist despite pharmacological acid suppression. Reflux monitoring has been traditionally performed through esophageal pH measurement to detect acid reflux (i.e., drops in esophageal pH to below 4.0). Multichannel intraluminal impedance and pH measurement constitutes an important development in reflux monitoring because, in addition to detecting acid reflux, it enables measurement of nonacid reflux (i.e., with a pH > 4.0, also known as ‘weakly acidic’ for pH > 4 but < 7, or ‘weakly alkaline’ if pH > 7), which may be responsible for symptoms in some patients who are being treated with proton pump inhibitors. This review describes the approach to measuring nonacid reflux, the possible mechanisms responsible for symptoms due to this type of reflux, the clinical importance of this phenomenon and available treatment options; and the role of multichannel intraluminal impedance and pH monitoring in the evaluation of refractory gastroesophageal reflux disease.     

多通道食管腔内阻抗-pH监测对胃食管反流性咳嗽的诊断价值

 目的 探讨多通道食管腔内阻抗-pH监测（MII-pH）对胃食管反流性咳嗽（GERC）的诊断价值和局限性。方法 选择2010年5月—2011年7月在同济大学附属同济医院呼吸内科门诊就诊的可疑GERC患者,进行MII-pH,并经药物抗反流治疗证实诊断。分析MII-pH对GERC诊断的灵敏度、特异度、假阳性率、假阴性率、总符合率、阳性预计值和阴性预计值,并计算AUC_ROC和Kappa值。结果 在接受MII-pH的56例患者中,35例结果阳性,30例（85.7%）确诊为GERC,其中酸反流引起者25例（83.3%）,非酸反流引起者5例（16.7%）。在21例MII-pH阴性结果患者中,有6例（28.6%）经药物抗反流治疗,GERC诊断得到证实。MII-pH对GERC的诊断灵敏度为83.3%,特异度75.0%,假阳性率25.0%,假阴性率16.7%,总符合率80.4%,阳性预测值85.7%,阴性预测值71.4%,AUC_ROC 0.792,Kappa值0.577。结论 MII-pH能识别包括非酸反流在内的所有GERC,是较灵敏可靠的GERC诊断手段。     

Inter‐observer agreement for multichannel intraluminal impedance–pH testing

Twenty‐four‐hour ambulatory multichannel intraluminal impedance (MII)–pH detects both acid and nonacid reflux (NAR). A computer‐based program (Autoscan?, Sandhill Scientific, Highlands Ranch, CO, USA) automates the detection of reflux episodes, increasing the ease of study interpretation. Inter‐observer agreement between multiple reviewers and with Autoscan? for the evaluation of significant NAR with MII–pH has not been studied in the adult population. Twenty MII–pH studies on patients taking a proton pump inhibitor twice daily were randomly selected. Autoscan? analyzed all studies using the same pre‐programmed parameters. Four reviewers interpreted the MII–pH studies, adding or deleting reflux episodes detected by Autoscan?. Positive studies for NAR and total reflux episodes were based on published criteria. Cohen's kappa statistic (κ) evaluated inter‐observer agreement between reviewers and Autoscan? analysis. The average κ for pathologic NAR between reviewers was 0.57 (0.47–0.70), and between reviewers and Autoscan? was 0.56 (0.4–0.8). When using the total reflux episode number as a marker for pathologic reflux (acid and NAR), the κ score was 0.72 (0.61–0.89) between reviewers, and 0.74 (0.53–0.9) when evaluating total reflux episodes. Two reviewers agreed more often with each other and with Autoscan? on the number of NAR episodes, while the other two reviewers agreed with each other, but did not agree with either Autoscan? or the first two reviewers. Inter‐observer agreement between reviewers and Autoscan? for detecting pathologic NAR is moderate, with reviewers either excluding more of the Autoscan?‐defined events or excluding fewer events and therefore agreeing with Autoscan?.     

Streamlining 24-hour pH study for GERD: Use of a 3-hour postprandial test

At present, the ambulatory 24-hr pH test has been used as a diagnostic tool to assess gastroesophageal reflux disease (GERD) in those patients with reflux symptoms and a normal endoscopy. However, patients poorly tolerate the prolonged nature of the 24-hr test. The aim of this study was to determine whether analyzing a 3-hr postprandial period from a full 24-hr study would be as sensitive as the longer test. Data were analyzed from a standard ambulatory 24-hr pH recording. A positive test was determined if the pH was <4 for more than 4% of the study period with the probe placed 5 cm above the lower esophageal sphincter for both groups. The data were then reanalyzed by determining the percent time of pH < 4 during a 3-hr postprandial period. The results of 50 patients with a positive 24-hr test were compared with 50 patients with normal tests. The meal that was used to study the 3-hr postprandial period occurred in the late afternoon or early evening. The 3-hr postprandial test had a sensitivity of 88% when compared to the 24-hour test and a specificity of 98%. The positive predictive value was 100% for the 3-hr test, and the accuracy of this shorter test when compared with the standard 24-hour test was 95%. In conclusion the 3-hr postprandial analysis is a highly sensitive and specific test for demonstrating GERD. By using the shorter test, patient discomfort may be reduced and compliance enhanced.     

Small volume acid reflux in gastroesophageal reflux disease patients with hiatal hernia is only detectable by pH‐metry but not by multichannel intraluminal impedance

Until now, it is uncertain if the so‐called pH‐only reflux episodes that consist of a pH drop without evidence of retrograde bolus movement in multichannel intraluminal impedance (MII) represent reflux episodes or artifacts. Hiatal hernia (HH) may allow reflux of small volumes to occur that can be detected by pH‐metry but not by MII. The aim was to search for a mechanism that can explain pH‐only reflux, 20 patients (12 females and 8 males, median age 52 years, interquartile range [IQR]: 40.5–60.75 years) were investigated with MII–pH off PPI. Impedance and pH‐metry data were analyzed separately. The differences in detection rate of acid reflux between pH‐metry and MII were correlated with the presence of HH. In an in vitro experiment, MII–pH probes were flushed with citric acid in plastic tubes of different size with capillary diameter and diameters of 2.5 mm and 4.5 mm, while recording pH values and impedance. HH was present in six patients and absent in 14 patients. In patients with HH in comparison with patients with absent HH, the difference of acid reflux detection between pH‐metry and MII is significantly higher (70%, IQR: 15–88% and 3.6%, IQR: 0–31%, respectively). In vitro all simulated reflux lead to a fall in pH whereas a corresponding decrease in impedance was only recognizable in the 4.5‐mm plastic tubes. Acid reflux episodes in patients with HH are more frequently detected by pH‐metry than by MII. Small volume reflux that does not lead to a decrease in impedance is the likely explanation for this phenomenon.     

Comparison of multichannel intraluminal impedance-p H monitoring and reflux scintigraphy in pediatric patients with suspected gastroesophageal reflux

AIM To evaluate the agreement of multichannel intraluminal impedance-p H monitoring(MII-p HM) and gastroesophageal reflux scintigraphy(GES) for the diagnosis of gastroesophageal reflux disease. METHODS Seventy-five consecutive patients with suspectedgastroesophageal reflux disease(GERD) underwent 24-h combined MII-p HM recording and one hour radionuclide scintigraphy during the course of the MIIpH M study. Catheters with 6 impedance channels and 1 p H sensor were placed transnasally. Impedance and p H data analysis were performed automatically and manually. For impedance monitoring, reflux was defined as a retrograde 50% drop in impedance, starting distally and propagating retrogradely to at least the next two more proximal measuring channels. Reflux index(RI, percentage of the entire record that esophageal p H is 4.0) greater than 4.2% for p HM and number of refluxes more than 50 for 24 h for MII were accepted as positive test results. At scintigraphy, 240 frames of 15 seconds duration were acquired in the supine position. Gastroesophageal reflux was defined as at least one reflux episode in the esophagus. After scintigraphic evaluation, impedance-pH recordings and scintigraphic images were evaluated together and agreement between tests were evaluated with Cohen's kappa.RESULTS Sufficient data was obtained from 60(80%) patients(34 male, 56.7%) with a mean age of 8.7 ± 3.7 years(range: 2.5-17.3 years; median: 8.5 years). Chronic cough, nausea, regurgitation and vomiting were the most frequent symptoms. The mean time for recording of MII-pH M was 22.8 ± 2.4 h(range: 16-30 h; median: 22.7 h). At least one test was positive in 57(95%) patients. According to diagnostic criteria, GERD was diagnosed in 34(57.7%), 44(73.3%), 47(78.3%) and 51(85%) patients by means of p HM, MII, GES and MII-p HM, respectively. The observed percentage agreements/κ values for GES and p HM, GES and MII, GES and MII-p HM, and MII and p HM are 48.3%/-0.118; 61.7%/-0.042; 73.3%/0.116 and 60%/0.147, respectively. There was no or slight agreement between GES and p HM alone, MII alone or MII-p HM. p H monitoring alone missed 17 patients compared to combined MII-p HM. The addition of MII to pH monitoring increased the diagnosis rate by 50%.CONCLUSION No or slight agreement was found among p H monitoring, MII monitoring, MII-pH monitoring and GES for the diagnosis of gastroesophageal reflux disease.     

Reflux profile of Chinese gastroesophageal reflux disease patients with combined multichannel intraluminal impedance-pH monitoring

Background and Aims:  To investigate the reflux profile of Chinese gastroesophageal reflux disease (GERD) patients with the aid of combined multichannel intraluminal impedance-pH (MII-pH) monitoring technique.
Methods:  Consecutive patients presented with GERD symptoms were enrolled to erosive esophagitis (EE) group, non-erosive reflux disease (NERD) group and functional heartburn (FH) group after upper endoscopy, combined MII-pH monitoring and rabeprazole test. Another 20 healthy controls (HC) were recruited.
Results:  Sixty-four GERD patients (EE:20, NERD:22, FH:22, HC:20) were enrolled. There were more episodes of liquid reflux and proximal reflux in EE and NERD groups than that in FH and HC groups ( P  < 0.05). Patients in FH and HC groups had higher proportion of mixed reflux ( P  = 0.000). The percentage of acid reflux in EE and NERD was much higher, while there was a higher percentage of weakly acidic reflux in FH and HC ( P  = 0.000). No significant difference was found in MII-pH parameters between groups with and without response to rabeprazole test except recumbent percentage time of esophageal pH value below 4 and episodes of proximal reflux.
Conclusion:  Erosive esophagitis and NERD patients had more liquid and proximal reflux episodes than FH patients and healthy controls. Acid and liquid reflux was predominant in the former two groups, while weakly acidic and mixed reflux was predominant in the latter two groups.     

Weakly acidic reflux

The advent of multichannel intraluminal impedance‐pH (MII‐pH) monitoring has generated interest in the role of weakly acidic reflux in persistent symptoms in patients with gastroesophageal reflux disease (GERD). Emerging evidence suggests that MII‐pH may be superior to conventional pH testing under certain circumstances in the detection of reflux and expert opinions have been put forth advocating a central role for pH impedance monitoring in the detection of GERD. However the clinical relevance of an impedance‐based diagnosis of reflux and its impact on clinically relevant outcomes is less clear. This review appraises the role of weakly acidic reflux in health and in GERD patients and the clinical utility of detecting weakly acidic reflux in the management of GERD.     

Objective assessment of gastroesophageal reflux after extended Heller myotomy and total fundoplication for achalasia with the use of 24‐hour combined multichannel intraluminal impedance and pH monitoring (MII‐pH)

SUMMARY. This study aims to evaluate by the use of 24‐hour combined multichannel intraluminal impedance and pH monitoring (MII‐pH) the efficacy of the Nissen fundoplication in controlling both acid and nonacid gastroesophageal reflux (GER) in patients that underwent Heller myotomy for achalasia. It has been demonstrated that fundoplication prevents the pathologic acid GER after Heller myotomy, but no objective data exists on the efficacy of this antireflux surgery in controlling all types of reflux events. The study population consisted of 20 patients that underwent laparoscopic Heller myotomy and Nissen fundoplication for achalasia. All patients were investigated with manometry and MII‐pH. MII‐pH showed no evidence of postoperative pathologic GER. The overall number of GER episodes was normal in both the upright and recumbent position. This reduction was obtained because of the postoperative control of both the acid and nonacid reflux episodes. The Nissen fundoplication adequately controls both acid and nonacid GER after extended Heller myotomy. Further controls with MII‐pH are warranted to check at a longer follow‐up for the efficacy of this antireflux procedure in achalasic patients.     

Gastroesophageal and laryngopharyngeal reflux detected by 24-hour combined impedance and pH monitoring in healthy Chinese volunteers

OBJECTIVE: To define the normative data of gastroesophageal reflux (GER) and laryngopharyngeal reflux (LPR) in healthy Chinese volunteers. METHODS: Healthy volunteers without gastrointestinal and throat disease and symptoms were enrolled and underwent 24‐hour impedance‐pH monitoring. RESULTS: A total of 37 healthy volunteers completed all the tests (female 54.1%; age 38.0 ± 15.2 years). Of 1862 GER, 49.6% were mixed, 40.9% were liquid and 9.5% were gas. More than half (54.9%) were acid. The median and 95th percentile numbers of GER were 52 and 71, respectively. The number of LPR was eight, of which two were mixed and the others were liquid. Only one episode of reflux was classified as acid LPR. The median and 95th percentile numbers of LPR were 0 and 2, respectively. More liquid reflux were associated with LPR (P = 0.02). Age had no influence on GER and LPR reflux profiles. CONCLUSIONS: Few LPR occurred in healthy Chinese volunteers and they were rarely acid when they reached the larynx. LPR was mostly associated with liquid reflux.     

Normal values of 24-h ambulatory intraluminal impedance combined with pH-metry in subjects eating a Mediterranean diet

BACKGROUND AND AIMS: Multichannel intraluminal impedance combined with pH-metry is a novel technique for studying gastro-oesophageal reflux. As refluxes are particularly frequent after meals, we carried out this study in order to assess the impact of a Mediterranean diet on normal values of impedancemetry. METHODS: Twenty-five Italian healthy subjects (13 men, median age 29 years, range 22-67 years) without reflux symptoms were recruited for this study. They underwent oesophageal 24-h impedance + pH-metry. A Mediterranean diet was given to all subjects on the day of examination and its total energy intake was 9668.5 kJ (2300 kcal). RESULTS: A total of 1518 refluxes were recorded during 24 h with more upright than recumbent episodes (median 15 versus 0; p<0.01). The median total acid exposure time was 0.5% (range 0-4.2%). Acid and weakly acidic refluxes were equally reported (49% versus 51%). Weakly acidic episodes were more frequent than acid ones during 1-h postprandial periods (68% versus 32%; p<0.0001). Liquid-only and mixed refluxes reached the proximal oesophagus (15 cm above lower oesophageal sphincter) in 42.6% of cases. Median acid clearing time was longer than median bolus clearing time (28 s versus 12 s; p<0.01). CONCLUSIONS: This study provides normal values of pH-impedancemetry in Italian people eating a Mediterranean diet and are suitable for comparative pathophysiological investigations on reflux patients who have dietary habits similar to those of our country.     

Utilization of wireless pH monitoring technologies: a summary of the proceedings from the Esophageal Diagnostic Working Group

Gastroesophageal reflux disease (GERD) can be difficult to diagnose – symptoms alone are often not enough, and thus, objective testing is often required. GERD is a manifestation of pathologic levels of reflux into the esophagus of acidic, nonacidic, and/or bilious gastric content. However, in our current evidence‐based knowledge approach, we only have reasonable outcome data in regards to acid reflux, as this particular type of refluxate predictably causes symptoms and mucosal damage, which improves with medical or surgical therapy. While there are data suggesting that nonacid reflux may be responsible for ongoing symptoms despite acid suppression in some patients, outcome data about this issue are limited. Therefore, this working group believes that it is essential to confirm the presence of acid reflux in patients with ‘refractory’ GERD symptoms or extraesophageal symptoms thought to be caused by gastroesophageal reflux before an escalation of antireflux therapy is considered. If patients do not have pathologic acid reflux off antisecretory therapy, they are unlikely to have clinically significant nonacid or bile reflux. Patients who do not have pathologic acid gastroesophageal reflux parameters on ambulatory pH monitoring then: (i) could attempt to discontinue antisecretory medications like proton pump inhibitors and H2‐receptor antagonists (which are expensive and which carry risks – i.e. C. diff, etc.); (ii) may undergo further evaluation for other causes of their esophageal symptoms (e.g. functional heartburn or chest pain, eosinophilic esophagitis, gastroparesis, achalasia, other esophageal motor disorders); and (iii) can be referred to an ear, nose, and throat/pulmonary/allergy physician for assessment of non‐GERD causes of their extraesophageal symptoms.     

Combined multichannel intraluminal impedance and pH monitoring is helpful in managing children with suspected gastro-oesophageal reflux disease

BackgroundGastro-oesophageal reflux is very common in the paediatric age group. There is no single and reliable test to distinguish between physiologic and pathological gastro-oesophageal reflux, and this lack of clear distinction between disease and normal can have a negative impact on the management of children.AimsTo evaluate the usefulness of 24-h oesophageal pH-impedance study in infants and children with suspected gastro-oesophageal reflux disease.MethodsPatients were classified by age groups (A–C) and reflux-related symptoms (typical and atypical). All underwent pH-impedance study. If the latter suggested an abnormal reflux, patients received therapy in accordance with NASPGHAN/ESPGHAN recommendations, while those with normal study had an additional diagnostic work-up. The efficacy of therapy was evaluated with a specific standardized questionnaire for different ages.ResultsThe study was abnormal in 203/428 patients (47%) while normal in 225/428 (53%). Of those with abnormal study, 109 exhibited typical symptoms (54%), and 94 atypical (46%). The great majority of the patients with abnormal study were responsive to medical anti-reflux therapy.ConclusionsWe confirm the utility of prolonged oesophageal pH-impedance study in detecting gastro-oesophageal reflux disease in children and in guiding therapy. Performing oesophageal pH-impedance monitoring in children with suspected gastro-oesophageal reflux disease is helpful to establish the diagnosis and avoid unnecessary therapy.     

Gastroesophageal reflux disease and patterns of reflux in patients with idiopathic pulmonary fibrosis using hypopharyngeal multichannel intraluminal impedance

Idiopathic pulmonary fibrosis (IPF) is a diffuse fibrotic lung disease of unknown etiology. The association between IPF and gastroesophageal reflux disease (GERD) has been suggested. The objective of this study was to determine the prevalence of GERD and assess the proximity of reflux events in patients with histologically proven IPF using hypopharyngeal multichannel intraluminal impedance (HMII). This is a retrospective review of prospectively collected data from patients with histologically confirmed IPF (via lung biopsy) who underwent objective esophageal physiology testing including high‐resolution manometry and HMII. Defective lower esophageal sphincter (LES) was defined as either LES pressure of <5.0 mmHg, total length of LES of <2.4 cm, or intra‐abdominal length of LES of <0.9 cm. Abnormal esophageal motility was considered present when failed swallows ≥30% and/or mean wave amplitude <30 mmHg was present. HMII used a specialized impedance catheter to directly measure laryngopharyngeal reflux (LPR) and full column reflux (reflux 2 cm distal to the upper esophageal sphincter). Based on the previous study of healthy subjects, abnormal proximal exposure was considered present when LPR ≥1/day and/or full column reflux ≥5/day were present. From October 2009 to June 2011, 46 patients were identified as having pulmonary fibrosis and sufficient HMII data. Of 46, 10 patients were excluded because of concomitant connective tissue diseases, and 8 patients were excluded because they had undergone lung transplantation, which may impact the patterns of reflux. The remaining 28 patients with histologically confirmed IPF (male 16, female 12) were included in this study. Mean age and BMI were 60.4 years (range, 41–78) and 28.4 (range, 21.1–38.1), respectively. All patients except one were symptomatic; 23 (82%) patients had concomitant typical GERD symptoms such as heartburn, whereas 4 (14%) patients had isolated pulmonary symptoms such as cough. Esophageal mucosal injury such as esophagitis and Barrett's esophagus was found in 17 (71%) patients, whereas hiatal hernia was found in 19 (73%) patients. Abnormal proximal exposure, which occurred almost exclusively in the upright position, was present in 54% (15/28) of patients. There was no significant difference in clinical symptoms, objective findings of GERD, and pulmonary functions such as forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and diffusing capacity of the lung for carbon monoxide (DLCO) between patients with and without abnormal proximal exposure. Although the total number of reflux events was significantly higher in patients with abnormal proximal exposure, a large number of patients had a negative DeMeester score regardless of whether abnormal proximal exposure was present (patients with, 80%; those without, 85%). Patients with abnormal proximal exposure more likely had a defective LES compared with those without (93% vs. 75%). Fourteen patients (56%) had abnormal esophageal motility including aperistaltic esophagus (n = 9). This first study of HMII in patients with IPF demonstrated that GERD is highly prevalent (>70%), and abnormal proximal reflux events such as LPR and full column reflux are common despite a frequently negative DeMeester score. HMII may be beneficial in the work‐up of GERD in patients with IPF.     

Acid gastroesophageal reflux and symptom occurrence

In 17 patients with esophagitis (degree I=erythema,N=10; degree II=erosions,N=7) esophageal pH was measured at 5 and 10 cm above the esophagogastric junction to assess whether the extension of acid reflux and the severity of the mucosal lesions could influence the association between reflux and symptoms. A minority of the refluxes were related with symptoms (4.0% and 7.7% in degree I, 14.1% and 12.0% in degree II at 5 and 10 cm respectively), whereas 65.4% and 100% of the symptoms were related with reflux in degrees I and II, respectively, with 76.5% and 35.7% occurring during refluxes reaching the proximal recording site. A relationship of symptoms with reflux is shown, particularly in erosive disease. Some reflux characteristics (extension, duration, acidity) seem to influence symptom occurrence mainly in mild esophagitis; however, more than 85% of the acid reflux episodes are symptom-free, regardless of the severity of the mucosal injury.     

How well can quantitative 24-hour intraesophageal pH monitoring distinguish various degrees of reflux disease?

Twenty-four normal subjects and 64 symptomatic patients with various degrees of reflux disease (24 with reflux symptoms without esophagitis and 21 with mild and 19 with severe esophagitis) underwent quantitative 24-hr intraesophageal pH monitoring. Various reflux parameters during supine, interprandial, and postprandial periods were examined by binary logistic regression and by CART analysis to determine the sensitivity and specificity to separate the various groups of subjects and patients. The distinction was excellent between asymptomatic controls and patients with severe erosive esophagitis (sensitivity and specificity both 100% by logistic regression and 95% and 88%, respectively, by CART), but discrimination was poor when asymptomatic controls were compared to symptomatic patients without esophagitis (71% and 79% by logistic regression and 75% and 92% by CART), which is the most important indication for pH recording in clinical practice. A 3-hr postprandial pH recording was inadequate to distinguish the various groups. The acidity of the reflux episodes during the night appeared to be a crucial factor in the development of severe erosive esophagitis. The duration of esophageal acid exposure was another important factor in the development of reflux lesions.