Empiric acid suppression with the "PPI test," widely used to assess whether upper-GI symptoms are due to gastroesophageal reflux disease, actually performs poorly as a predictor of GERD, Dr. Peter Bytzer and his colleagues wrote in the December issue of Clinical Gastroenterology and Hepatology.
Typically, clinicians perform a PPI test to diagnose GERD without the need for endoscopy. They give patients a 2-week course of a proton pump inhibitor and then determine whether the brief treatment ameliorated upper GI symptoms. If so, the symptoms are assumed to be acid related, said Dr. Bytzer of Copenhagen University and his associates.
But in their study, such a PPI test "showed a disappointingly low validity" for diagnosing GERD, and couldn’t reliably distinguish between reflux esophagitis and nonerosive reflux disease. Even when combined with a clinical diagnosis made by a primary care physician, a clinical diagnosis made by a gastroenterologist, or the results of a detailed diagnostic questionnaire, the outcome of a PPI test didn’t add reliable information allowing clinicians to separate patients who had GERD from those who did not, the researchers said (Clin. Gastroenterol. Hepatol. 2012 [doi:10.1016/j.cgh.2012.06.030]).
Dr. Bytzer and his colleagues analyzed data originally collected in the DIAMOND clinical trial, an international study that found the Reflux Disease Questionnaire to be useful in diagnosing GERD among patients who consulted primary care physicians because of frequent upper GI symptoms. The DIAMOND study results indicated that unlike the Reflux Disease Questionnaire, PPI testing had very limited diagnostic value.
Dr. Bytzer and his associates performed more detailed analyses of the data, using different combinations of three main symptoms (heartburn, central chest pain, and dysphagia or regurgitation); different definitions of "PPI response"; and assessments of various subgroups of patients, all in the hope of improving the diagnostic yield of PPI testing. They compared the diagnostic usefulness of PPI testing against state-of-the-art comprehensive diagnostic work-ups for GERD in 299 of the DIAMOND study subjects.
"This large database provides the best platform so far to test whether there are better approaches for scoring a test of PPI therapy," the investigators noted.
All of the subjects underwent endoscopy with concomitant wireless esophageal pH monitoring and symptom assessment. They then completed the detailed Reflux Disease Questionnaire, and participated in a 2-week PPI test using esomeprazole (Nexium), during which they recorded GI symptoms in a diary.
A total of 69% of the patients who did have GERD showed a positive response to the PPI test. This means that 31% of the study participants with GERD were not identified by PPI testing.
Moreover, 51% of the patients who did not have GERD also showed a positive response to the PPI test, the investigators said.
Both patients who had GERD and patients who did not reported that their symptom response to acid suppression increased over the course of the first 5-6 days of treatment and then leveled off for the remaining 8-9 days.
The PPI test performed only marginally better across various subgroups of patients, such as those with GERD plus reflux esophagitis (as compared with patients who had GERD but no reflux esophagitis) or those whose physicians were certain of their GERD diagnosis (compared with patients whose physicians were uncertain about their GERD diagnosis).
For example, 48% of the study participants whose physicians predicted that they had GERD showed a positive response on PPI testing – a rate that was nearly identical to the 47% of study subjects whose physicians predicted that they had some disorder other than GERD.
Similarly, the PPI test performed only marginally better when different symptom combinations and different definitions of "PPI response" were assessed.
"In line with other researchers, we found that ... the clinical value of [the PPI test] is very limited," Dr. Bytzer and his colleagues said.
This study was funded by AstraZeneca. Dr. Bytzer reported ties to AstraZeneca, Boehringer Ingelheim, Eisai, Nycomed, Reckitt Benckiser, Takeda, and Wyeth, and his associates reported ties to numerous industry sources, including employment by AstraZeneca.
