Addition of esophageal impedance monitoring to pH monitoring increases the yield of symptom association analysis in patients off PPI therapy

BACKGROUND: The additional yield of esophageal impedance monitoring in identification of reflux as the cause of reflux symptoms is unknown. OBJECTIVES: To compare the yield of symptom-reflux association analysis of combined esophageal pH-impedance data with the yield of analysis of pH data alone. METHODS: In 60 patients with symptoms of heartburn and regurgitation combined, 24-h pH-impedance monitoring was performed. Acid-suppressive medication was stopped 1 wk in advance. Patients (48) with at least one symptom during the measurement period were selected for further analysis. Patients were instructed to note the time and nature of their symptoms. Eleven types of reflux episodes were defined, based on combinations of magnitude of the pH drop, nadir pH, and nature of the refluxate (gas and liquid) on impedance tracings. Symptom association analysis-symptom index, the symptom sensitivity index, and the symptom association probability (SAP)-was performed for each definition of reflux. RESULTS: The proportion of patients with a positive SAP (> or =95.0%) varied between 62.5% and 77.1%, depending on the definition of reflux episodes. When both pH and impedance parameters were used to identify reflux, a higher proportion of patients had a positive SAP than with pH alone (77.1%vs 66.7%, p < 0.05). Symptom association analysis for acidic and weakly acidic reflux separately did not result in a higher yield than analysis with all reflux episodes pooled, regardless of pH. CONCLUSION: In patients off proton pump inhibitor, the addition of impedance monitoring to esophageal pH monitoring leads to an increase in the proportion of patients in whom an association between reflux episodes and symptoms can be identified.     

Step‐by‐step management of refractory gastresophageal reflux disease

Up to a third of the patients who receive proton pump inhibitor (PPI) once daily will demonstrate lack or partial response to treatment. There are various mechanisms that contribute to PPI failure and they include residual acid reflux, weakly acidic and weakly alkaline reflux, esophageal hypersensitivity, and psychological comorbidity, among others. Some of these underlying mechanisms may coincide in the same patient. Evaluation for proper compliance and adequate dosing time of PPIs should be the first management step before ordering invasive diagnostic tests. Doubling the PPI dose or switching to another PPI is the second step of management. Upper endoscopy and pH testing appear to have limited diagnostic value in patients who failed PPI treatment. In contrast, esophageal impedance with pH testing (multichannel intraluminal impedance MII‐pH) on therapy appears to provide the most insightful information about the subsequent management of these patients (step 3). In step 4, treatment should be tailored to the specific underlying mechanism of patient's PPI failure. For those who demonstrate weakly acidic or weakly alkaline reflux as the underlying cause of their residual symptoms, transient lower esophageal sphincter relaxation reducers, endoscopic treatment, antireflux surgery and pain modulators should be considered. In those with functional heartburn, pain modulators are the cornerstone of therapy.     

Extraesophageal gastroesophageal reflux disease (GERD) symptoms are not more frequently associated with proximal esophageal reflux than typical GERD symptoms

Extraesophageal (EE) symptoms such as cough and throat clearing are common in patients referred for reflux testing, but are less commonly associated with gastroesophageal reflux disease (GERD). Patients with reflux associated EE symptoms often lack typical GERD symptoms of heartburn and regurgitation. Our aim was to compare the frequency of proximal esophageal reflux between esophageal (typical) symptoms and EE (atypical) symptoms. Combined multichannel intraluminal impedance‐pH (MII‐pH) tracings were blinded by an investigator so that symptom markers were relabeled with a number without disclosure of symptom type. We selected 40 patients with at least five reflux‐related symptom events for one of four symptoms (heartburn, regurgitation, cough, or throat clearing). A blinded investigator analyzed all 200 reflux episodes, reporting the proximal esophageal extent of the reflux for all symptoms. The percentage of symptom‐related reflux extending proximally to 17 cm above the LES was similar among all four symptom types. At least 50% of all symptoms were associated with proximal esophageal reflux to 17 cm, with regurgitation having the highest frequency at 60%. Our data indicate that EE symptoms are not more frequently associated with proximal esophageal reflux than typical esophageal symptoms.     

Intra‐bolus pressure and esophagogastric gradient,assessed with high‐resolution manometry,are associated with acid exposure and proximal migration of refluxate

Trans‐sphincteric pressure gradient (TSPG) seems to play a relevant role in eliciting refluxes during transient lower esophageal sphincter relaxations (TLESRs). Intra‐bolus pressure (IBP) is considered to be correlated to esophageal wall tone. We aimed to evaluate the relationship between IBP, TSPG during TLESRs and the dynamic properties of refluxate in gastroesophageal reflux disease. Sixteen non‐erosive reflux disease (NERD), 10 erosive disease (ERD) patients and 12 healthy volunteers (HVs), underwent 24‐hour impedance‐pH monitoring and combined high‐resolution manometry‐impedance before and 60 minutes. After a meal, ERD patients presented a significantly lower mean IBP (4.7 ± 1.6 mmHg) respect to NERD patients (8.9 ± 2.8 mmHg) and HVs (9.2 ± 3.2 mmHg). NERD patients with physiological abnormal acid exposure time showed a mean IBP (10.4 ± 3.1 mmHg) significantly higher than that in NERD with pathological abnormal acid exposure time (5.1 ± 1.5 mmHg). The TSPG value was significantly higher during TLESRs accompanied by reflux than during TLESRs not associated with reflux, both in patients and in HVs. A significant direct correlation was found between IBP, TSPG and proximal spread of refluxes in patients and in HVs. Gastroesophageal reflux disease patients display different degrees of esophageal distension. An increased compliance of the distal esophagus may accommodate larger volumes of refluxate and likely facilitates the injuries development. Higher TSPG values appear to facilitate the occurrence of refluxes during TLESRs. In patients with NERD, higher TSPG and IBP values favor proximal spread of refluxate and hence may play a relevant role in symptom generation.     

An algorithm for diagnosis and treatment of refractory GERD

Patients with gastro-esophageal reflux disease (GERD) who are not responding to proton pump inhibitors (PPIs) given once daily are very common. These therapy-resistant patients have become the new face of GERD in clinical practice in the last decade. Upper endoscopy appears to have a limited diagnostic value. In contrast, esophageal impedance with pH testing on therapy appears to provide the most insightful information about the subsequent management of these patients. Commonly, doubling the PPI dose or switching to another PPI will be offered to patients who failed PPI once daily. Failure of such therapeutic strategies is commonly followed by assessment for weakly or residual acidic reflux. There is growing information about the potential value of compounds that can reduce transient lower esophageal sphincter relaxation rate. Esophageal pain modulators are commonly offered to patients with functional heartburn although supportive clinical studies are still missing.     

How many cases of laryngopharyngeal reflux suspected by laryngoscopy are gastroesophageal reflux disease-related?

AIM: To investigate the prevalence of gastroesophageal reflux disease (GERD) in patients with a laryngoscopic diagnosis of laryngopharyngeal reflux (LPR).METHODS: Between May 2011 and October 2011, 41 consecutive patients with laryngopharyngeal symptoms (LPS) and laryngoscopic diagnosis of LPR were empirically treated with proton pump inhibitors (PPIs) for at least 8 wk, and the therapeutic outcome was assessed through validated questionnaires (GERD impact scale, GIS; visual analogue scale, VAS). LPR diagnosis was performed by ear, nose and throat specialists using the reflux finding score (RFS) and reflux symptom index (RSI). After a 16-d wash-out from PPIs, all patients underwent an upper endoscopy, stationary esophageal manometry, 24-h multichannel intraluminal impedance and pH (MII-pH) esophageal monitoring. A positive correlation between LPR diagnosis and GERD was supposed based on the presence of esophagitis (ERD), pathological acid exposure time (AET) in the absence of esophageal erosions (NERD), and a positive correlation between symptoms and refluxes (hypersensitive esophagus, HE).RESULTS: The male/female ratio was 0.52 (14/27), the mean age ± SD was 51.5 ± 12.7 years, and the mean body mass index was 25.7 ± 3.4 kg/m². All subjects reported one or more LPS. Twenty-five out of 41 patients also had typical GERD symptoms (heartburn and/or regurgitation). The most frequent laryngoscopic findings were posterior laryngeal hyperemia (38/41), linear indentation in the medial edge of the vocal fold (31/41), vocal fold nodules (6/41) and diffuse infraglottic oedema (25/41). The GIS analysis showed that 10/41 patients reported symptom relief with PPI therapy (P < 0.05); conversely, 23/41 did not report any clinical improvement. At the same time, the VAS analysis showed a significant reduction in typical GERD symptoms after PPI therapy (P < 0.001). A significant reduction in LPS symptoms. On the other hand, such result was not recorded for LPS. Esophagitis was detected in 2/41 patients, and ineffective esophageal motility was found in 3/41 patients. The MII-pH analysis showed an abnormal AET in 5/41 patients (2 ERD and 3 NERD); 11/41 patients had a normal AET and a positive association between symptoms and refluxes (HE), and 25/41 patients had a normal AET and a negative association between symptoms and refluxes (no GERD patients). It is noteworthy that HE patients had a positive association with typical GERD-related symptoms. Gas refluxes were found more frequently in patients with globus (29.7 ± 3.6) and hoarseness (21.5 ± 7.4) than in patients with heartburn or regurgitation (7.8 ± 6.2). Gas refluxes were positively associated with extra-esophageal symptoms (P < 0.05). Overall, no differences were found among the three groups of patients in terms of the frequency of laryngeal signs. The proximal reflux was abnormal in patients with ERD/NERD only. The differences observed by means of MII-pH analysis among the three subgroups of patients (ERD/NERD, HE, no GERD) were not demonstrated with the RSI and RFS. Moreover, only the number of gas refluxes was found to have a significant association with the RFS (P = 0.028 and P = 0.026, nominal and numerical correlation, respectively).CONCLUSION: MII-pH analysis confirmed GERD diagnosis in less than 40% of patients with previous diagnosis of LPR, most likely because of the low specificity of the laryngoscopic findings.     

Impedance-pH Monitoring for Diagnosis of Reflux Disease: New Perspectives

Heartburn is the most specific symptom of gastroesophageal reflux disease (GERD). In clinical practice, heartburn relief by a proton pump inhibitor (PPI) trial does suffice to confirm GERD. However, an objective diagnosis of GERD is required before anti-reflux endoscopic or surgical interventions, independently from PPI response. Thus, since normal findings at upper endoscopy are detected in the majority of patients with heartburn, reflux monitoring is often required. When traditional catheter-based or wireless pH tests are used, reflux episodes are conventionally identified by pH drops below 4.0 units. Combined impedance-pH monitoring has the advantage to provide a comprehensive assessment of both physical and chemical properties of refluxate and the distinction between acid and weakly acidic refluxes, both proven to cause heartburn. Unfortunately, the conventional impedance-pH parameters, namely acid exposure time and number of reflux events, are characterized by suboptimal diagnostic sensitivity, and the reliability of symptom–reflux association indexes remains questionable. Therefore, novel impedance parameters, namely the post-reflux swallow-induced peristaltic wave (PSPW) index and the mean nocturnal baseline impedance (MNBI), have recently been proposed in order to achieve a better diagnostic yield. In fact, they proved to be highly accurate in distinguishing reflux-related from reflux-unrelated heartburn, off- as well as on-PPI therapy. Currently, manual review of impedance-pH tracings is needed because of the modest accuracy of available software tools for automated analysis. PSPW index and MNBI are highly applicable and reproducible, and their calculation requires a few additional minutes during the manual review of impedance-pH tracings. So far, we believe that PSPW index and MNBI are ready for prime time and should become part of the standard analysis of impedance-pH tracings for GERD diagnosis in patients with endoscopy-negative heartburn.     

Weakly acidic reflux in patients with chronic unexplained cough during 24 hour pressure, pH, and impedance monitoring

BACKGROUND AND AIMS: Acid gastro-oesophageal reflux is one of the most important causes of chronic cough. The response to acid suppression in these patients is not as good as in patients with heartburn but improvement with antireflux surgery has been reported, suggesting the involvement of a non-acidic gastric component in the refluxate. Less acidic reflux may produce symptoms such as regurgitation or chest pain. We investigated whether chronic cough might be associated with weakly acidic reflux. METHODS: We studied 28 patients with chronic cough using 24 hour ambulatory pressure-pH-impedance monitoring. Manometry was used for precise recognition of cough and impedance-pHmetry to detect acid (pH <4), weakly acidic (pH 7-4), and weakly alkaline (impedance drops, pH >/=7) reflux. A symptom association probability (SAP) analysis was performed for each type of reflux. RESULTS: Analysis was completed in 22 patients with 24 cough events (5-92)/patient. The majority of cough events (69.4%) were considered "independent" of reflux whereas 30.6% occurred within two minutes of a reflux episode. Half of these (49%) were "reflux cough" sequences, involving acid (65%), weakly acidic (29%), and weakly alkaline (6%) reflux. Ten patients (45%) had a positive SAP between reflux and cough: five with acid, two with acid and weakly acidic, and three only with weakly acidic reflux. CONCLUSIONS: Ambulatory pressure-pH-impedance monitoring with SAP analysis allowed precise determination of the temporal association between cough and gastro-oesophageal reflux (acid, weakly acidic, and weakly alkaline) and identification of a subgroup of patients with chronic cough clearly associated with weakly acidic gastro-oesophageal reflux.     

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.     

Characteristics of symptomatic reflux episodes in Japanese proton pump inhibitor-refractory non-erosive reflux disease patients

AIM: To clarify the pathogenesis of gastroesophageal reflux disease symptoms in non-erosive reflux disease(NERD) patients.METHODS: Thirty-five NERD patients with persistent symptoms, despite taking rabeprazole 10 mg twice daily for at least 8 wk, were included in this study. All patients underwent 24 h combined impedance- p H on rabeprazole. The symptom index(SI) was considered to be positive if ≥ 50%, and proximal reflux episodes were determined when reflux reached 15 cm above the proximal margin of the lower esophageal sphincter.RESULTS: In 14(40%) SI-positive patients, with liquid weakly acid reflux, the occurrence rate of reflux symptoms was significantly more frequent in proximal reflux episodes(46.7%) than in distal ones(5.7%)(P 0.001). With liquid acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes(38.5%) and distal ones(20.5%)(NS). With mixed liquid-gas weakly acid reflux, the occurrence rate of reflux symptoms in proximal reflux episodes was significantly more frequent(31.0%) than in distal reflux ones(3.3%)(P 0.001). With mixed liquid-gas acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes(29.4%) and distal ones(14.3%)(NS).CONCLUSION: The proximal extent of weakly acidic liquid and mixed liquid-gas reflux is a major factor associated with reflux perception in SI-positive patients on proton pump inhibitor therapy.     

Acid and non-acid gastro-esophageal refluxes in children with chronic pulmonary diseases

OBJECTIVES: Acid gastro-esophageal reflux has been shown associated with chronic pulmonary diseases. The role of non-acid refluxes in these children is still unknown. Therefore we investigated the prevalence of acid and non-acid refluxes, and their association with desaturations, in children with chronic pulmonary symptoms. METHODS: In 25 children aged 6 months to 15 years with unexplained chronic cough, wheeze or sputum production, refluxes were assessed by 24h-multiple intra-esophageal impedance measurements, simultaneous pH metry and continuous recording of oxygen saturation. RESULTS: pH in the proximal and distal esophagus as well as six impedance channels were evaluated in all subjects. A mean of 129.4 refluxes per day per patient was detected. Complete and technically usable readings of oxygen saturation were obtained in 14 children. In this group the subjects had a mean of 112.6 refluxes and 92.6 desaturations per day per patient. The symptom index and symptom sensitivity index for acid refluxes were 34.7% and 24.6%, respectively, for non-acid refluxes 3.0% and 66.7%, respectively. CONCLUSIONS: We found a high prevalence of acid reflux and a very low number of non-acid refluxes in this population. The symptom index was negative for all types of reflux, whereas the symptom sensitivity index was positive for both acid and non-acid reflux. Our data support a relation between acid gastro-esophageal refluxes and chronic pulmonary symptoms; however, this study does not support a role of non-acid reflux in children with respiratory symptoms, which are not on antacid medication.     

联合食管多通道腔内阻抗-pH监测在诊断胃食管反流病中的价值

目的 了解联合食管多通道腔内阻抗pH(MII-pH)监测诊断胃食管反流病(GERD)的价值.方法 纳入具有烧心症状且食管黏膜无损伤患者44例,首先行MII-pH监测,然后行14 d的雷贝拉唑试验(试验结束时烧心症状完全消失定义为雷贝拉唑试验阳性).70名健康志愿者行MII-pH监测的结果作为正常值进行参照.结果 根据食管pH监测存在异常食管酸暴露或酸反流症状指数(SI)阳性者20例(45.4%).MII-pH监测提示弱酸反流SI阳性者2例,据此检查诊断烧心患者GERD的比例增至50%(22/44).雷贝拉唑试验阳性4例,据此则将烧心患者诊断为GERD的比例增至54.5%(24/44).结论 联合食管MII-pH监测可增加GERD检出率.     

联合食管多通道腔内阻抗-pH监测在诊断胃食管反流病中的价值

目的 了解联合食管多通道腔内阻抗pH(MII-pH)监测诊断胃食管反流病(GERD)的价值.方法 纳入具有烧心症状且食管黏膜无损伤患者44例,首先行MII-pH监测,然后行14 d的雷贝拉唑试验(试验结束时烧心症状完全消失定义为雷贝拉唑试验阳性).70名健康志愿者行MII-pH监测的结果作为正常值进行参照.结果 根据食管pH监测存在异常食管酸暴露或酸反流症状指数(SI)阳性者20例(45.4%).MII-pH监测提示弱酸反流SI阳性者2例,据此检查诊断烧心患者GERD的比例增至50%(22/44).雷贝拉唑试验阳性4例,据此则将烧心患者诊断为GERD的比例增至54.5%(24/44).结论 联合食管MII-pH监测可增加GERD检出率.     

Gastroesophageal reflux symptoms not responding to proton pump inhibitor: GERD,NERD, NARD,esophageal hypersensitivity or dyspepsia?

Gastroesophageal reflux (GER) is a common gastrointestinal process that can generate symptoms of heartburn and chest pain. Proton pump inhibitors (PPIs) are the gold standard for the treatment of GER; however, a substantial group of GER patients fail to respond to PPIs. In the past, it was believed that acid reflux into the esophagus causes all, or at least the majority, of symptoms attributed to GER, with both erosive esophagitis and nonerosive outcomes. However, with modern testing techniques it has been shown that, in addition to acid reflux, the reflux of nonacid gastric and duodenal contents into the esophagus may also induce GER symptoms. It remains unknown how weakly acidic or alkaline refluxate with a pH similar to a normal diet induces GER symptoms. Esophageal hypersensitivity or functional dyspepsia with superimposed heartburn may be other mechanisms of symptom generation, often completely unrelated to GER. Detailed studies investigating the pathophysiology of esophageal hypersensitivity are not conclusive, and definitions of the various disease states may overlap and are often confusing. The authors aim to clarify the pathophysiology, definition, diagnostic techniques and medical treatment of patients with heartburn symptoms who fail PPI therapy.     

Bravo （wireless） ambulatory esophageal pH monitoring： How do day 1 and day 2 results compare？

AIM： To investigate if differences exist for patients＇ gastroesophageal reflux as measured by the Bravo ambulatory esophageal pH system between d 1 and d 2.
METHODS： A retrospective study of 27 consecutive adult patients who underwent Bravo esophageal pH monitoring was performed. Patients underwent EGD under Ⅳ conscious sedation prior to Bravo placement. Acid reflux variables and symptom scores for d 1 were compared to d 2.
RESULTS： The mean doses of fentanyl and midazolam were 90.4 μg and 7.2 mg, respectively. D 1 results were significantly more elevated than d 2 with respect to total time pH 〈 4, upright position reflux, and mean number of long refluxes. No statistical difference was noted between the two days for supine position reflux, number of refluxes, duration of longest reflux, episodes of heartburn, and symptom score.
CONCLUSION： Patients undergoing Bravo esophageal pH monitoring in association with EGD and moderate conscious sedation experience significantly more acid reflux on d i compared to d 2. The Ⅳ sedation may be responsible for the increased reflux on d 1. Performed this way, 48-h Bravo results may not be entirely representative of the patients＇ true GE reflux profile.     

Heartburn refractory to proton-pump inhibitors

Opinion statement The most appropriate diagnostic and therapeutic approach to patients with heart-burn that persists despite the use of proton-pump inhibitor (PPI) therapy currently is not known. In general, patients with heartburn refractory to PPIs may have more than one explanation for their persistent symptoms. These include uncontrolled esophageal acid exposure (“PPI failure”) in a small subset of patients, as well as other potential etiologies in the majority of patients who have controlled esophageal acid exposure on PPI therapy (“PPI success”). Some potential explanations for persistent heartburn in this latter group include hypersensitivity to acid reflux, nonacidic or duodenogastric esophageal reflux, as well as functional heartburn. Patients who present with heartburn refractory to PPIs should be investigated further to determine the potential cause. We believe the diagnostic modality with the most clinical usefulness is 24-hour pH and multichannel intraluminal impedance monitoring with symptom index performed while the patient is on high-dose PPI therapy. This approach allows the patient to be properly categorized and also identifies a substantial proportion of patients who will have functional heartburn, a condition that should discourage the use of endoscopic or surgical therapies. Therapeutic options for patients with heartburn refractory to PPIs are limited and have not been thoroughly studied. As a result of the paucity of information, we favor a therapeutic approach based on the outcome of diagnostic testing.     

Refractory heartburn to proton pump inhibitors: epidemiology, etiology and management

Patients with refractory heartburn to proton pump inhibitors (PPIs) represent a distinctive group which is difficult to manage. In a systematic review of the relative literature we found that approximately 20% of patients with erosive esophagitis and 15-25% of patients with normal endoscopy and abnormal 24-hour esophageal pH monitoring continue to report heartburn despite treatment with standard dose PPIs. Furthermore, approximately 30-40% of patients with normal endoscopy and 24-hour pH studies and 15-20% of patients with Barrett's esophagus have refractory heartburn to double dose PPIs. In such cases, compliance to therapy, duodeno-gastroesophageal reflux, gastro-esophageal motility disorders and eradication of Helicobacter pylori infection may contribute to symptoms. Based on the available evidence, we suggested an algorithm for the evaluation and management of these patients.     

The utility of ambulatory pH monitoring in patients presenting with chronic cough and asthma.

OBJECTIVE: To evaluate the prevalence of gastroesophageal reflux disease (GERD) in patients presenting with asthma and chronic cough. PATIENTS AND METHODS: The charts of 358 consecutive patients who were referred for ambulatory gastroesophageal pH monitoring to the Lung Centre in Vancouver, British Columbia, were reviewed, and the data of 108 (30%) patients with asthma and 134 (37%) patients with chronic cough were analyzed. The maintenance treatment for GERD was discontinued before patients underwent the pH monitoring study. One hundred eighteen (33%) patients were excluded. RESULTS: Reflux episodes identified reflux events as the percentage of time where the pH was less than four. For asthma patients, 70 (64.8%) had distal total reflux, 50 (46.3%) had distal upright reflux, 41 (38.3%) had distal supine reflux and 73 (67.6%) had other distal refluxes. Proximal total reflux in asthmatic patients was present in 56 (52%), proximal upright reflux in 55 (51%) and proximal supine reflux in 56 (52%) patients. For chronic cough patients, 70 (52.6%) had distal total reflux, 59 (44.4%) had distal upright reflux, 45 (34.4%) had distal supine reflux and 75 (56%) patients had other distal refluxes. In chronic cough patients, proximal total reflux was present in 70 (52%), proximal upright reflux in 80 (60%) and proximal supine reflux in 59 (44%). Presenting respiratory and/or reflux symptoms were absent in approximately 25% of patients with asthma and reflux, and in approximately 50% of patients with chronic cough and reflux. During pH monitoring, symptoms did not differ significantly between those with and without distal reflux in both study groups, except for more significant heartburn in patients with chronic cough and reflux (RR 2.0). CONCLUSIONS: The data of the present study support the observation that there is a high prevalence of GERD in patients with asthma or chronic cough. The use of different pH parameters for detecting acid reflux during 24 h ambulatory pH monitoring, such as proximal esophageal acid measurement, should be considered as part of the routine interpretation of such testing. A low threshold for diagnosing GERD in patients with asthma or chronic cough is essential, because respiratory and/or reflux symptoms can be absent or atypical in some of these patients.     

How to manage refractory GERD

Patients who are unresponsive to 4-8 weeks' treatment with PPIs twice daily might have so-called refractory GERD. The first investigation these patients should undergo is upper endoscopy to exclude a diagnosis of peptic ulcer disease or cancer and identify the presence of esophagitis. The presence of esophagitis in these patients is suggestive of a pill-induced injury, an autoimmune skin disease involving the esophagus, eosinophilic esophagitis or, less likely, a hypersecretory syndrome or a genotype that confers altered metabolism of PPIs. Refractory reflux syndromes associated with normal endoscopy findings are more problematic to diagnose and further testing may be required, including prolonged 48 h pH testing, impedance measurements (for nonacid reflux), esophageal manometry and gastric function tests. For patients with refractory GERD who do not have esophagitis, possible etiologies include nocturnal gastric acid breakthrough, nonacid GER, missed GER or other diseases such as achalasia, gastroparesis or functional heartburn.     

Effect of proton-pump inhibitor treatment on symptoms and quality of life in GERD patients depends on the symptom-reflux association

BACKGROUND: Gastroesophageal reflux disease patients demonstrate various pathophysiologic backgrounds. Therefore, a heterogeneous response to proton-pump inhibitor (PPI) treatment can be expected. We investigated the effect of short-term PPI treatment on symptoms and quality of life (QOL) in primary care patients with and without pathologic esophageal acid exposure and in presence or absence of a positive association between symptoms and reflux episodes. STUDY: Seventy-four heartburn patients were categorized into 4 groups according to positive or negative symptom-reflux association, as expressed in symptom index, symptom sensitivity index, and symptom association probability (SAP) and presence or absence of pathologic reflux, defined as esophageal pH<4%>6% of the time (pH+/pH-). Overall and specific reflux symptoms were assessed 1 week before and the last week during a 2-week course of 40-mg esomeprazole daily. The QOL was scored by the Quality of Life in Reflux and Dyspepsia questionnaire 2 weeks before treatment and directly after. RESULTS: Using the SAP to assess symptom-reflux associations, the 4 groups [SAP+pH+(n=40); SAP+pH-(n=12); SAP-pH+(n=10); SAP-pH-(n=10)] had similar demographic characteristics. The SAP-pH- subgroup had the least overall symptom reduction (P<0.01) and in the SAP+pH+ subgroup the greatest heartburn symptom reduction was found (P<0.02). The residual symptom scores on treatment were lowest in SAP+pH+ and highest in SAP-pH- subgroups and relatively high in the SAP+pH-. QOL was severely reduced and SAP-pH- patients had the lowest QOL overall. Similar findings were made using symptom index and symptom sensitivity index. CONCLUSIONS: Symptomatic reflux patients without evidence of reflux disease on a 24-hour pH recording responded less favorably to PPI treatment than patients with a positive symptom-reflux association or with pathologic reflux.