The development and advancement of ambulatory esophageal pH monitoring has provided a key tool with which pathologic esophageal acid exposure can be objectively measured; although not perfect, it provides the clinician with arguably the most important piece of information in the diagnosis and management of patients with gastroesophageal reflux disease. It is also important to emphasize that, although esophageal pH monitoring can reliably measure esophageal acid exposure, assessing the relationship of abnormal findings and the patients’ symptoms is a much more complex matter and, of course, the key to successful treatment outcomes.
Key points
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Physicians should have a general knowledge of the diagnostic accuracy of each pH monitoring method.
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Prolonged pH monitoring and the combined impedance function increase the amount of information available for esophageal acid exposure evaluation; however, their effects on gastroesophageal reflux disease (GERD) diagnosis and clinical management are still under ongoing investigation.
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Prolonged pH monitoring increases the reflux detection rate.
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Because of the complexity of GERD diagnosis, routine pH monitoring should be performed for patients who are undergoing evaluation for antireflux surgery.
Introduction
The first link between gastric acid and gastroesophageal reflux (GER) was reported in 1884 after the retrieval of an acid-contained sponge from the esophagus of a patient with heartburn. The association between esophageal mucosal damage and the presence of acidic juice in the esophagus slowly emerged over the early part of the twentieth century. In 1958, Tuttle and Grossman first measured esophageal acid reflux using an existing gastric pH meter with manometry. Johnson and DeMeester established the foundation of esophageal pH monitoring in 1974 after studying GER in normal subjects and patients with reflux symptoms. In this landmark study, not only the methodology of esophageal pH monitoring and the normal reference values were defined but also a composite scoring system, the DeMeester score, was created to quantify acid exposure using 6 pH parameters. This scoring system has been widely validated and is used today. With the advancement of technology, the sponge was replaced by glass and then antimony electrode catheters and in the 1990s to a wireless implantable capsule; but the concept of esophageal pH monitoring for the evaluation of GER disease (GERD) has not changed over the past hundred years. The aims of this article are to review the current methods of ambulatory esophageal pH monitoring, compare the advantage and disadvantage of each test, and to discuss current controversies of each method in an effort to elucidate future directions in the diagnosis of GERD.
Introduction
The first link between gastric acid and gastroesophageal reflux (GER) was reported in 1884 after the retrieval of an acid-contained sponge from the esophagus of a patient with heartburn. The association between esophageal mucosal damage and the presence of acidic juice in the esophagus slowly emerged over the early part of the twentieth century. In 1958, Tuttle and Grossman first measured esophageal acid reflux using an existing gastric pH meter with manometry. Johnson and DeMeester established the foundation of esophageal pH monitoring in 1974 after studying GER in normal subjects and patients with reflux symptoms. In this landmark study, not only the methodology of esophageal pH monitoring and the normal reference values were defined but also a composite scoring system, the DeMeester score, was created to quantify acid exposure using 6 pH parameters. This scoring system has been widely validated and is used today. With the advancement of technology, the sponge was replaced by glass and then antimony electrode catheters and in the 1990s to a wireless implantable capsule; but the concept of esophageal pH monitoring for the evaluation of GER disease (GERD) has not changed over the past hundred years. The aims of this article are to review the current methods of ambulatory esophageal pH monitoring, compare the advantage and disadvantage of each test, and to discuss current controversies of each method in an effort to elucidate future directions in the diagnosis of GERD.
Esophageal pH monitoring: what, why, and when
Esophageal pH monitoring is a direct in vivo measurement of esophageal acid exposure over time for the evaluation of GERD. It can be currently performed using either catheter-based or wireless systems ( Fig. 1 ). Catheter-based pH monitoring requires transnasal placement of the catheter, with its measuring electrode located 5 cm above the manometrically measured upper border of lower esophageal sphincter (LES). A wireless-based pH capsule is generally placed endoscopically, 6 cm above the squamocolumnar junction (SCJ), or in the setting of Barrett esophagus above the top of the gastric rugal folds. The pH recordings of 24 hours, 48 hours, or 96 hours are currently possible, depending on the choice of device (catheter vs wireless), patient tolerability, and the duration a capsule remains attached. In the case of wireless monitoring, the pH data (sampled at a frequency of once every 6 seconds) are transmitted to an external radiofrequency recorder and then transferred to a computer with commercial software allowing automatic and/or manual analysis. Patients are generally asked to keep a diary recording symptoms, body positions, and meal periods during the time of pH monitoring allowing the analysis of reflux patterns and symptom correlation measures. Fig. 2 demonstrates the basic steps of the test. Currently available and widely used pH monitoring options are listed in Box 1 .
Catheter based (transnasal placement at 5 cm above upper border of LES)
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Conventional 24-hour catheter pH monitoring; dual-channel pH monitoring
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24-hour multichannel intraluminal impedance pH monitoring
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Wireless based (endoscopic placement at 6 cm above SCJ)
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48-hour Bravo (Given Imaging Ltd, Yoqneam, Israel) pH monitoring
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96-hour Bravo pH monitoring
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Esophageal pH monitoring is a crucial part of GERD evaluation. According to the 2007 American College of Gastroenterology’s practice guidelines for esophageal reflux testing, pH monitoring
- 1.
Is useful in documenting abnormal esophageal reflux exposure in endoscopy-negative patients with typical reflux symptoms who failed medical therapy and are being considered for antireflux surgery
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May be useful in detecting the adequacy of acid control in patients with Barrett esophagus, atypical reflux symptoms, or recurrent symptoms after antireflux surgery
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May be useful when combined with impedance in detecting nonacid reflux or in evaluating patients whose reflux symptoms are not controlled by a proton pump inhibitor (PPI; PPI nonresponders)
Patients presenting with typical reflux symptoms are given the diagnosis of GERD liberally by health care providers from many specialties. Studies have shown that symptoms, reflux or hiatal hernia detected by barium esophagram, and even findings of mucosal injury on endoscopy are either unreliable or not sensitive in diagnosing GERD; thus, esophageal pH monitoring becomes an integral part of the diagnostic and treatment plan. The Diamond study, a single-blind prospective study of 308 patients published in 2010, concluded that the Reflux Disease Questionnaire, family practitioners, and gastroenterologists all had similar diagnostic accuracy for GERD (sensitivity 62%–67%; specificity 63%–70%). In this study, the 48-hour Bravo (Given Imaging Ltd, Yoqneam, Israel) pH-monitoring result, endoscopic findings of esophagitis, symptom association probability (SAP) of 95% or more, or the borderline pH-monitoring result with response to PPI therapy were used as the gold standard for diagnosis. A consensus panel of esophageal experts serving as a diagnostic advisory panel concluded in 2012 that the optimal preoperative diagnostic workup for GERD should include pH testing along with upper endoscopy, barium esophagram, and manometry. A diagnostic algorithm outlining the decision making and test selection process when evaluating patients suspected to have abnormal esophageal acid exposure is shown in Fig. 3 .
Test selection
A variety of methodologies are available to assess esophageal pH exposure. Single-sensor catheter-based antimony pH probes provide the traditional and heretofore most widely used method. Conventionally, this is a 24-hour study, which detects distal esophageal acid exposure. Dual-channel 24-hour catheter-based pH monitoring provides data on proximal esophageal exposure, although fixed distances between the pH sensors results in misplacement of the proximal probe in as many as 45% of patients, limiting its usefulness. Two significant technological advances were made in the 1990s. First, combined impedance-pH catheters were developed, allowing the assessment of the role of nonacid reflux particularly in patients with atypical and/or refractory reflux symptoms (multichannel intraluminal impedance pH monitoring [MII-pH], Fig. 4 A). Second, wireless implantable pH sensors were developed, allowing ambulatory recording of 48 hours and now up to 96 hours in the absence of a transnasal catheter (see Fig. 4 B). The investigators recommend that patients with typical GERD symptoms, such as heartburn and regurgitation, should undergo at least a conventional pH study given the poor sensitivity and specificity of symptom-based diagnosis of GERD. In contrast to common belief, a trial of PPI for symptom response does not improve the diagnostic accuracy. The optimal strategy for test selection should be based on presenting symptoms (typical or atypical), availability, and perhaps response to PPI. Table 1 compares the advantages and disadvantages of each testing method.
| pH-Monitoring Test | Pro and Con for Test Selection Consideration |
|---|---|
| Catheter-based | |
| 24-h conventional |
|
| MII-pH |
|
| Wireless-based | |
| 48-h Bravo |
|
| 96-h Bravo |
|
Test interpretation
All patients who undergo pH monitoring are required to fast 6 to 8 hours and to be off antacid medications for 5 to 7 days before catheter or capsule placement. On-therapy (stay on antacid medications) tests can also be done and are most commonly performed on patients who have refractory reflux symptoms. The widely accepted cutoff of a pH less than 4 defining a reflux episode is from Tuttle and colleagues’ original work in 1961. It is based on the fact that the onset of pyrosis was induced when the distal esophagus was exposed to acidic fluid perfusion at a pH less than 4 and the acidic acid dissociation constant (pKa) of pepsin. Many recommend dietary restrictions, although further studies are needed to evaluate its effect on pH monitoring results. Parameters reported are listed in Box 2 . Published normal values for the catheter-based and wireless systems are summarized in Table 2 .
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