Alimentary TractThe proton pump inhibitor test for gastroesophageal reflux disease: Optimal cut-off value and duration
Introduction
Gastro-oesophageal reflux disease (GERD) is a common condition, affecting 10–30% of the population in Western countries [1], which encompasses a broad spectrum of clinical manifestations, ranging from mild or troublesome episodes of heartburn and acid regurgitation without breaks in the oesophageal mucosa to severe oesophagitis and its complications.
Although GERD has little impact on prognosis, with an annual mortality rate of approximately 1 death per 100,000 patients [2] and no effect on life expectancy even in severe cases [3], the disease causes substantial morbidity; complications develop in up to 20% of patients and quality of life can be greatly impaired [4], [5].
It has suggested that, at least in the case of the typical reflux syndrome, a diagnosis can be reached on the basis of characteristic symptoms, with no need for diagnostic testing [6], [7]. In fact, upper GI endoscopy, which is the gold standard for diagnosing oesophageal mucosal injury, actually fails to recognize as many as 50% of patients with GERD because they have no mucosal lesions [8]. On the other hand, the detection of abnormal oesophageal acid exposure by means of a 24-h pH monitoring has only a limited sensitivity for GERD diagnosis [9], which however may be slightly increased by measuring the association between symptoms and reflux episodes, using a symptom index [10].
For many years it has been suggested that a pharmacological test, i.e. the so-called PPI (proton pump inhibitor) test [11], might be useful for diagnosing GERD, particularly in the setting of primary care. The test consists of measuring the symptomatic response to a high-dose PPI treatment administered for 1–2 weeks in patients with GERD symptoms. The rationale for using short-term, high-dose PPI administration as a diagnostic tool is based on the strong effect of PPIs on inhibition of gastric acid secretion, healing erosive oesophagitis [12] and improving GERD symptoms. As the test aims at establishing that the patient's symptoms are acid-related, the dosage for the PPI test is higher than usual (in most studies, a double dose) in order to obtain a greater inhibitory effect on acid secretion [13]. No definitive consensus about the duration of the PPI test has been reached; in most studies the duration is 7–14 days [14]. As far as the interpretation of the test is concerned, a positive response is usually considered on the basis of main symptom (ordinarily heartburn) improvement and cut-off values between 50% and 75% of symptom improvement have been claimed to provide the best diagnostic accuracy [15].
We designed a multicenter study in patients with typical GERD symptoms with or without erosive oesophagitis, with the aim of assessing the usefulness of a short trial of high-dose PPI as a diagnostic test, and to determine (1) the optimal duration of PPI administration and (2) the best cut-off value of symptomatic response. To overcome the absence of a “hard” criterion to classify non-erosive reflux disease (NERD) as “true” GERD patients, which is needed to calculate sensitivity and specificity of the PPI test, we used the outcome after 3-months of therapy with standard PPI doses as an independent diagnostic criterion; accordingly, patients completely asymptomatic after this period of PPI therapy were classified as “true” GERD patients and vice versa.
Section snippets
Methods
This study is a national multicenter collaborative investigation (the EMERGE project). The study was conducted on GERD patients with typical symptoms only, between June 2004 and June 2006 according to the rules of Good Clinical Practice. All Ethics Committees of participating centers granted authorization and written informed consent was obtained from all patients.
Five hundred and forty-four adult GERD patients (265 females and 279 males, mean age 43.5 ± 12.4 years) were recruited by 59
Results
Of the 544 patients recruited, 304 (55.8%) had endoscopic oesophagitis while the remaining 240 (44.2%) showed no oesophageal mucosal damage (see Table 1). The main clinical and demographic characteristics of patients are presented in Table 1.
Forty-seven patients (8.7%) left the study prematurely: 7 for personal reasons unrelated to therapy, 27 for no-show or delay in presenting at follow-up visit, 13 for unspecified reasons; thus, 497 patients (91.3%) completed the entire study period, 276 with
Discussion
The lack of a gold diagnostic standard for GERD is commonly acknowledged [23]. Among the tools available for diagnosis, endoscopy, ambulatory pH monitoring and the PPI test are those most frequently used. Upper endoscopy has shown to have rather a good specificity with value ranging from 90% to 95% [23], but the sensitivity in patients with typical GERD symptoms is only around 50%, due to the fact that a percentage from 50% to 70% of patients in fact do not show any oesophageal mucosal damage
Conflict of interest
None.
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Cited by (19)
Advancements in the use of 24-hour impedance-pH monitoring for GERD diagnosis
2022, Current Opinion in PharmacologyCitation Excerpt :However, they are not used routinely in daily clinical practice and are generally reserved to screening patients that have to be recruited for clinical trials [13]. Symptom response to a short (2–4 weeks) course of once-daily oral administration of PPIs has been proposed as a simple and practical method to diagnose GERD [14]. This test can be reasonable in the appropriate setting (e.g. primary care), but it must be borne in mind that its limitations are relevant [15].
A SIGE-SINGEM-AIGO technical review on the clinical use of esophageal reflux monitoring
2020, Digestive and Liver DiseaseCitation Excerpt :However, it is well known that most patients (> 70%) show no abnormalities on endoscopic examination. An empirical trial of PPIs should be considered as part of the diagnostic workup for suspected GERD, always paying attention to the right indication and to stop the PPIs when not necessary [67–69]. Also, proper dosing and compliance must be assured, and, if only partial improvement is seen, some studies support using twice daily dosing or switching to another PPI before declaring the patient a “non-responder” [70,71].
Symptom Predictability in Gastroesophageal Reflux Disease and Role of Proton Pump Inhibitor Test
2014, Gastroenterology Clinics of North AmericaCitation Excerpt :There is a benefit to obtaining the RDQ score: based on a cutoff RDQ score of greater than 15, patients with GERD with typical symptoms (heartburn, regurgitation central chest pain, and dysphagia) had a greater proportion of responders (69%) versus patients with atypical (dyspepsia) symptoms (38%).10 In terms of duration of the PPI test, based on the work of de Leone and colleagues27 and Bytzer and colleagues,29 the response to the PPI plateaus at day 7 of therapy (Fig. 4). The PPI test does not have the performance characteristics of an acceptable diagnostic test to establish or exclude a diagnosis of GERD.
Diagnostic Accuracy of the Proton Pump Inhibitor Test in Gastroesophageal Reflux Disease and Noncardiac Chest Pain: A Systematic Review and Meta-analysis
2023, Journal of Clinical GastroenterologyTowards a better diagnosis of gastro esophageal reflux disease
2023, Expert Review of Gastroenterology and Hepatology