GERD Testing: Conduct Off Therapy

Gastroesophageal reflux disease (GERD) testing has evolved ever since the initial introduction of the catheter-based pH test more than half a century ago. More accurate pH measurements and improved patient tolerability were achieved by reducing the catheter’s diameter and stiffness, and the catheter-based pH test has continued to improve over the years.1 Introduction of the wireless pH capsule and subsequent impedance-pH testing have diversified our GERD-testing armamentarium and improved our methods for collecting data.

The wireless pH capsule provides several important advantages over the catheter-based pH test, and these include improved patient tolerability (no nasal intubation), 96-hour recording, fixed-position catheters (no catheter movements), more specific and directed placement, and the potential to place more than one capsule. The main advantage of the impedance-pH test is its capability to identify what was originally termed as “nonacidic reflux” (weakly acidic, neutral or weakly alkaline reflux), its correlation with symptoms, and the physical characteristics of the refluxate (gas, liquid, mixed).2

Performing the pH tests off therapy allows us to determine the underlying disorder responsible for a patient’s GERD-like symptoms.

One of the most common questions I receive from colleagues, referring physicians and participants at regional and national meetings is if these tests should be performed on or off antireflux treatment (primarily proton pump inhibitors [PPIs]). In this opinion piece, I argue we should perform GERD testing off treatment. In general, testing should be considered only if it is assumed the results of the test will alter the patient’s management and, thus, the patient’s clinical outcome. Furthermore, testing should be considered in a specific clinical scenario, when the likelihood of providing valuable results is relatively high. Several studies have demonstrated the limited value of pH tests (catheter based or capsule) in GERD patients who are treated with once-or twice-daily PPI. In a study of 70 GERD patients who failed PPI once daily, 64 percent had normal pH tests, suggesting the pH test has little value for explaining residual symptoms.3 Furthermore, if any pH test is performed in a patient who failed PPI twice daily, the current definition of refractory GERD, the likelihood of having a positive pH test has been shown to be as low as 7 percent.4 Thus, performing any of the aforementioned invasive pH tests does not provide useful information to help improve management and clinical outcomes for more than 90 percent of patients with refractory symptoms who failed PPI twice daily.

The impedance-pH test, on the other hand, was developed and promoted to evaluate GERD patients who failed PPI therapy while they were still on PPI therapy. Studies have shown that PPI treatment promotes the occurrence of nonacidic reflux, which can be determined by measuring resistance to electrical conductivity between two adjacent rings on the impedance catheter while refluxate is moving orally. However, the clinical value of the impedance-pH test has been limited by the need to demonstrate positive indexes (symptoms index and symptomassociation probability).5 Until now, the importance of documenting an abnormal degree of nonacidic reflux in the absence of a positive correlation between a patient’s symptoms and reflux events remained controversial. Many gastroenterologists (including me) will not offer any therapeutic intervention in this situation, which occurs in many patients undergoing impedance-pH testing. In a subset of patients who failed PPI twice daily, the impedance-pH test demonstrates positive symptom indexes, suggesting nonacidic reflux might be the possible cause for the patient’s GERD-related symptoms. Unfortunately, treatment in this clinical scenario has been very limited and relatively disappointing, thus necessitating a different clinical approach.6

Thus far, we have learned that pH testing on treatment is a low-yield procedure that provides very little value for understanding a patient’s residual symptoms. Even impedancepH testing on treatment often results in negative symptom indexes. This is due to a lack of positive correlation or complete absence of symptoms during the study. In the subset of patients with positive symptom indexes, treatment directed toward nonacidic reflux has been greatly disappointing.

Performing the pH tests (capsule or catheter based) off therapy allows us to determine the underlying disorder responsible for a patient’s GERD-like symptoms. In the last several decades, we have recognized that GERD phenotypes (Barrett’s esophagus, erosive esophagitis and nonerosive reflux disease) and functional esophageal disorders (functional heartburn and reflux hypersensitivity) can present with similar GERD-like symptoms. This is especially true for heartburn.7 However, proper management is different between the two groups and among the disorders in each group, supporting the importance of identifying the underlying disorder of a patient who failed PPI treatment. As we move from Barrett’s esophagus to erosive esophagitis and nonerosive reflux disease, reflux hypersensitivity and functional heartburn, the role of gastroesophageal reflux in generating patient symptoms decreases, and the role of esophageal hypersensitivity increases.8 The recent introduction of the Rome IV criteria for functional esophageal disorders supported the introduction of a new functional esophageal disorder termed “reflux hypersensitivity.”9 Reflux hypersensitivity has been defined as retrosternal symptoms, including heartburn and chest pain, in patients with normal endoscopy and lack of eosinophilic esophagitis and/or major esophageal motor disorders. In this group, there should be evidence of symptoms triggered by reflux events despite normal acid exposure. Recent data in heartburn patients who failed PPI twice daily suggest that more than 90 percent fall into either the functional heartburn or reflux hypersensitivity group.10 Furthermore, even with GERD phenotypes, nonerosive reflux disease is responsible for most PPI treatment failures. All support the importance of determining the underlying phenotypic presentation of GERD or functional esophageal disorder of a patient who failed PPI treatment.

One caveat to my argument is a patient who failed PPI treatment but was found to have GERD after a full evaluation with upper endoscopy and pH testing while off treatment in the past. The value of studying these types of patients off treatment is very low, as we already know their GERD phenotypes. Consequently, in this situation, GERD testing should be done on antireflux treatment.

Dr. Fass has a retainer agreement with Ironwood Pharmaceuticals; has provided lectures sponsored by AstraZeneca plc, Dr. Reddy’s Laboratories Ltd., Mederi Therapeutics Inc. and Takeda Pharmaceuticals U.S.A., Inc.; and has received research support from Ironwood Pharmaceuticals and Evoke Pharma, Inc.

1.Hershcovici, T., Gasiorowska, A., Fass, R. Advancements in the Analysis of Esophageal pH Monitoring in GERD. Nat Rev Gastroenterol Hepatol. 2011;8(2):101–7.
2.Maine, L., Tutuian, R., Shay, S., Vela, M., et al, Acid and Non-Acid Reflux in Patients With Persistent Symptoms Despite Acid Suppressive Therapy: A Multicenter Study Using Combined Ambulatory Impedance-pH Monitoring. Gut. 2006;55(10):1398–402.
3.Bautista, J.M., Wong, W.M., Pulliam, G., Esquivel, R.F., Fass, R.The Value of Ambulatory 24 Hr Esophageal pH Monitoring in Clinical Practice in Patients Who Were Referred With Persistent Gastroesophageal Reflux Disease (GERD)-Related Symptoms While on Standard Dose Anti-Reflux Medications. Dig Dis Sci.2005;50(10):1909–15.
4.Charbel, S., Khandwala, F., Vaezi, M.F.The Role of Esophageal pH Monitoring in Symptomatic Patients on PPI Therapy. Am J Gastroenterol. 2005;100(2):283–9.
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7.Fass, R. Distinct Phenotypic Presentations of Gastroesophageal Reflux Disease: A New View of the Natural History. Dig Dis. 2004;22(2):100–7.
8.Farmer, A.D., Ruffle, J.K., Aziz, Q. The Role of Esophageal Hypersensitivity in Functional Esophageal Disorders. J Clin Gastroenterol. 2017;51(2):91–99.
9.Aziz, Q., Fass, R., Gyawali, C.P., Miwa, H., Pandolfino, J. E., Zerbib, F. Functional Esophageal Disorders. Gastroenterology. 2006;130(5):1459–65.
10.Roman, S., Keefer, L., Imam, H., Korrapati, P., Mogni, B., Eident, K., Pandolfino, J.E., et al, Majority of Symptoms in Esophageal Reflux PPI Non-Responders Are Not Related to Reflux. Neurogastroenterol Motil. 2015;27(11):1667–74.

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