Alimentary Tract
The proton pump inhibitor test for gastroesophageal reflux disease: Optimal cut-off value and duration

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Abstract

Background

There is no accepted gold standard for the diagnosis of gastroesophageal reflux disease (GERD).

Aim

To assess the optimal cut-off value and duration of the proton pump inhibitor (PPI) test in GERD patients with and without oesophagitis.

Methods

Prospective study of 544 patients undergoing upper GI endoscopy and treated for 2 weeks with PPIs at double dose, and for 3 additional months at standard dose. The status of the patient at end of treatment was used as an independent diagnostic standard, i.e. patients completely asymptomatic were considered as “true” GERD patients.

Results

PPI test was positive in 89.7–97.8% of the patients according to the cut-off or duration of test used. Test sensitivity ranged from 95.5% to 98.8%, whereas specificity did not exceed 36.3%. Positive predictive values ranged from 87% to 80%, negative predictive values ranged from 58% to 70%, respectively.

Conclusions

The PPI test is a sensitive but poorly specific test in GERD patients. Its optimal duration is 1 week, and the optimal cut-off value is a decrease of heartburn score ≥75%. The diagnostic yield is higher in erosive oesophagitis compared with non-erosive reflux disease patients, similarly to the symptomatic response to 3-month PPI therapy.

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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