« Previous Next »Clinical Gastroenterology and Hepatology
Volume 6, Issue 8 , Pages 840-841, August 2008

Reflux Testing in the 21st Century: Is There a Role for pH Only?

published online 01 July 2008.

Article Outline

References
Copyright

In November 2002, a group of international experts met in Porto, Portugal for the express purpose of critically evaluating the available techniques to measure gastroesophageal reflux (GER). The consensus conclusion from this “Porto Meeting” was that “impedance monitoring is the most sensitive test for the detection of all types of reflux.”¹ This raised the question of whether it would become the new gold standard for GER monitoring. During the subsequent 5–6 years, there have been numerous studies showing that impedance changes recorded at multiple sites within the esophagus can identify postprandial reflux of a non-acid or “weakly acidic” nature that was undetected by an accompanying pH electrode in patients both on and off proton pump inhibitor (PPI) therapy.², ³ In addition, studies with ambulatory monitoring with combined multichannel intraluminal impedance and pH (MII-pH) for up to 24 hours in patients with persistent gastroesophageal reflux disease (GERD)–related symptoms have confirmed that considerable reflux having a pH >4.0 can be identified, and that a positive association of non-acid reflux with symptoms occurs in 30%–40% of patients identified as “PPI failures.”⁴, ⁵

In this issue of Clinical Gastroenterology and Hepatology, Kline et al⁶ describe the results of 24-hour testing with combined MII-pH in a group of 37 patients with persistent heartburn or regurgitation despite antisecretory therapy who had negative endoscopy and prior normal 24-hour pH-metry. The combined reflux testing revealed that 8 patients (16%) had excessive acid exposure detected by the pH electrode, 10 patients (27%) had an “acid sensitive esophagus” identified by a positive symptom index (SI) with normal total acid exposure, 14 patients (38%) exhibited a positive SI for non-acid reflux, and 7 patients (18%) exhibited no relationship of reflux with their continuing symptoms. The authors conclude that “just over half of the patients received a diagnosis that could not have been achieved with any form of pH testing, suggesting a potential role of MII-pH testing in the difficult to manage patient with GERD-like symptoms and no evidence of an association with acid reflux.”

The findings reported by Kline et al⁶ come as no surprise in a gastrointestinal community in which combined MII-pH monitoring has arguably become the new gold standard for detection of reflux. The multicenter study by Mainie et al⁵ of 168 patients with persistent reflux symptoms despite twice daily PPI therapy showed an identical frequency of positive SI for non-acid reflux at 37% and no reflux/symptom relationship in an additional 52% of the patients. The low frequency of acid reflux–related symptoms in this observation (11%) is explained by the MII-pH testing being performed while continuing high-dose PPI therapy, as opposed to studies off therapy reported by Kline et al.⁶ The report by Zerbib et al⁴ from the French/Belgium consortium multicenter study provides data to bring the 2 above observations into focus. Zerbib et al⁴ used ambulatory MII-pH testing to study patients with persistent symptoms on PPI therapy. For the 79 patients who were studied while off therapy, a higher prevalence of acid reflux–related symptoms (51%) and less non-acid–related symptoms (24%) was found in contrast to 71 patients studied while continuing PPI therapy in whom 20% exhibited a positive symptom association with acid reflux episodes, and 32% had association with non-acid reflux. Interestingly, the latter figure is very similar to that reported by both Mainie et al and Kline et al.⁶ It seems quite clear that as suggested from the Porto meeting, combined MII-pH monitoring provides the technology and the opportunity to obtain a more complete picture of reflux and its relation to patients' symptoms that was only being partially shown with pH monitoring alone.

The report by Kline et al⁶ and the prior reports by Mainie et al⁵ and Zerbib et al⁴ with larger numbers of patients raised an important question. Why would one test a patient with a technology that measures pH only now that ambulatory MII-pH has become a reality in testing worldwide? Some have suggested that a baseline pH study performed off antisecretory therapy would provide similar results to combined MII-pH testing. This report by Kline et al⁶ would seem to refute that suggestion. Not only did the pH findings fail to identify 38% of the patient group with a positive SI for non-acid reflux, but the additional 18% of patients with symptoms having no relationship to any type of reflux remained unresolved with pH monitoring alone. In addition, Kline et al⁶ report the interesting observation that the initial pH only study performed in these patients provided what would appear to be 18% false-negative results because the subsequent testing with combined MII-pH showed abnormal acid reflux in these patients. Perhaps of greater importance, the inadequacy of ambulatory pH monitoring is becoming increasingly clear as more publications support the ability to identify all types of reflux, both acid and non-acid, and relate these to ongoing symptoms by using combined MII-pH monitoring. Not only is this low sensitivity for reflux apparent, but the recent study by Hila et al⁷ demonstrated an additional lack of specificity for pH only–detected apparent reflux because of the artifact produced by ingestion of acidic materials. A further concern with baseline pH only testing off therapy is that it still fails to identify a group of patients potentially found within the “pH positive” group who might have persistent symptoms while taking PPI who would fall in the no reflux–related group as shown by Kline et al.⁶ The value of finding a negative SI for reflux should provide the opportunity to direct further evaluation and management of those patients toward other diagnoses, including functional heartburn in many. Only by use of a test that identifies all types of reflux can one have greater certainty that reflux in any form has been exonerated as the cause of the patient's persistent symptoms. The symptom relationship to reflux episodes has become more important clinically in clarifying the potential cause of persistent symptoms on PPI therapy. As shown by Kline et al,⁶ 27% of patients had a positive SI but a normal pH study on the basis of acid exposure time.

The question of what approach provides the most meaningful measure of the symptom/reflux association is very controversial, ie, is the SI or the symptom association probability (SAP) preferred? Kline et al⁶ chose the SI because it is easily calculated and has been shown to have excellent sensitivity in patients with esophagitis. Our experience with the results of fundoplication for treatment of patients on the basis of a positive SI has revealed a 93% success rate with 14-month postsurgical follow-up.⁸ In addition, comparison of the SI and SAP in the multicenter study of 168 patients revealed only fair correlation (kappa = 0.3). Although conceptually the more rigorous statistical association provided by the SAP appears attractive, the computer algorithm used to determine how this analysis is performed during the course of a 24-hour study varies between laboratories, and most individuals using this parameter do not know the details of the computer program used in their laboratory. We too agree with Kline et al⁶ that the SI is “easily calculated” and, in addition, is directly observed during analysis of the ambulatory monitoring study.

Since the introduction of PPIs as therapeutic options for the treatment of GERD, there has been a major paradigm shift in the approach to this disease. Before PPI availability, 1989 in the United States, the acid-related pathogenesis of GERD was paramount in our thinking. Thus, pH monitoring identifying acid exposure times and reflux scores were important identifiers of GERD. Acid-related complications such as severe erosive esophagitis and peptic strictures were common. With the availability of medications that could profoundly inhibit acid secretion, there was a slow recognition that symptoms possibly related to GERD might persist despite adequate acid control. Although healing of esophagitis and decreased prevalence of strictures had occurred, a growing recognition of patients with persistent symptoms despite therapy began to develop. Often suspected as a reasonable possibility, identification of non-acid reflux and its relationship to the symptoms in these PPI failures only became possible with the development of clinically useful ambulatory monitoring to detect non-acid reflux. Thus, MII-pH has evolved as a likely new gold standard to clarify the total picture of reflux/symptom relationships. In the 21st century the approach to a patient with possible GERD symptoms usually begins with a trial of PPI therapy, and I believe that it should include ambulatory MII-pH monitoring to identify ongoing reflux/symptom relationships in the PPI failures (Figure 1). Although endoscopy is often performed in these patients, it is likely to be normal in approximately 90% of cases,⁹ an observation that underscores the clinical value of MII-pH monitoring.

- View Large Image
- Download to PowerPoint
Figure 1.
GERD diagnostic algorithm.

As the emphasis in reflux testing has shifted from acid exposure and mucosal injury to clarifying the relationship between the patients' symptoms and reflux episodes of all types, the concept of a possible “sensitive esophagus” has emerged. This diagnostic entity is identified in the patient having a positive SI with a normal amount of reflux, usually measured as normal acid exposure time. Kline et al⁶ identified an acid-sensitive esophagus in 18% of their patients. Our experiences with ambulatory MII-pH monitoring performed on PPI therapy in patients with persistent symptoms have revealed a similar finding. From 200 consecutive patients monitored with MII-pH while on twice daily PPI, a positive SI combined with a normal total number of reflux episodes was noted in 61 patients (30.5%).

How should ambulatory reflux monitoring be performed in the 21st century? The study by Kline et al⁶ and those that have preceded it provide positive evidence to support the conclusion that MII-pH monitoring has become the gold standard for the measurement of reflux of all types. One has to question why anyone would use pH monitoring alone. If they do, they need to be aware of its limitations.

Back to Article Outline

References

Sifrim D, Castell D, Dent J, et al. Gastro-oesophageal reflux monitoring: review and consensus report on detection and definitions of acid, non-acid, and gas reflux. Gut. 2004;53:1024–1031

Vela MF, Camacho-Lobato L, Srinivaisan R, et al. Simultaneous intraesophageal impedance and pH measurement of acid and nonacid gastroesophageal reflux: effect of omeprazole. Gastroenterology. 2001;120:1599–1606

Wenzl TG. Investigating esophageal reflux with the intraluminal impedance technique. J Pediatr Gastroenterol Nutr. 2002;34:261–268

Zerbib F, Roman S, Roppert A, et al. Esophageal pH impedance monitoring and symptom analysis in GERD: a study of patients off and on therapy. Am J Gastroenterol. 2006;101:1956–1963

Mainie I, Tutuian R, Shay S. Acid and non-acid reflux in patients with persistent symptoms despite acid suppressive therapy: a multicentre study using combined ambulatory impedance-pH monitoring. Gut. 2006;55:1398–1402

Kline MM, Ewing M, Simpson N, et al. The Utility of Intraluminal Impedance in Patients With Gastroesophageal Reflux Disease–Like Symptoms But Normal Endoscopy and 24-Hour pH Testing. Hepatol. 2008;6:880–885
- View In Article

Hila A, Agrawal A, Castell DO. Combined multichannel intraluminal impedance and pH esophageal testing compared to pH alone for diagnosing both acid and weakly acidic gastroesophageal reflux. Clin Gastroenterol Hepatol. 2007;5:172–177

Mainie I, Tutuian R, Agrawal A, et al. Combined multichannel intraluminal impedance pH monitoring to select patients with persistent gastro-oesophageal reflux for laparoscopic Nissen fundoplication. Br J Surg. 2006;93:1483–1487