Intragastric Acidification Reduces the Occurrence of False-Negative Urea Breath Test Results in Patients Taking a Proton Pump Inhibitor W. D. Chey, M.D., F.A.C.P., F.A.C.G., K. V. Chathadi, M.D., J. Montague, F. Ahmed, M.D., and U. Murthy, M.D. University of Michigan Health System, Ann Arbor, Michigan; and Syracuse Veterans Administration Medical Center, Syracuse, New York OBJECTIVE: The aim of this study was to investigate whether reducing intragastric pH, at the time of urea ingestion, decreases the likelihood of false-negative (FN) urea breath test (UBT) results in patients taking a proton pump inhibitor (PPI). METHODS: Patients with active Helicobacter pylori infec- tion underwent a baseline 14 C-UBT (UBT-1) followed by treatment with lansoprazole 30 mg/day for 14 to 16 days. On day 13, patients returned for a repeat standard UBT (UBT- 2). Between days 14 to 16, patients underwent a modified UBT (UBT-3), which included consuming 200 ml of 0.1 N citrate solution 30 min before and at the time of 14 C-urea administration. Breath samples were collected 10 and 15 min after 14 C-urea ingestion. Mean 14 CO 2 excretion and the number of FN and equivocal UBT results were compared for the three UBTs. RESULTS: A total of 20 patients completed the study. Lan- soprazole caused a significant decrease in mean breath 14 CO 2 excretion (disintegrations per minute) between UBT-1 (2.96  0.23) and UBT-2 (2.08  0.52, p  0.05). Lansoprazole caused six (30%) FN and eight (40%) equiv- ocal UBT-2 results. Mean breath 14 CO 2 excretion for UBT-3 (677  514) was greater than for UBT-2 (234  327, p = 0.001). UBT-3 caused only two (10%) FN and three (15%) equivocal results. The 15-min breath sample caused fewer FN and equivocal results than the 10-min sample for both UBT-2 and UBT-3. CONCLUSIONS: Giving citrate before and at the time of 14 C-urea administration increases mean breath 14 CO 2 excre- tion and decreases FN and equivocal UBT results in patients taking a PPI. These observations suggest that it may be possible to design a UBT protocol that will remain accurate in the face of PPI therapy. (Am J Gastroenterol 2001;96: 1028 –1032. © 2001 by Am. Coll. of Gastroenterology) INTRODUCTION Recent guidelines support the use of the “test-and-treat” strategy for Helicobacter pylori (H. pylori) as initial man- agement for young patients with uninvestigated dyspepsia (1, 2). In this strategy, patients with dyspepsia who are under the age of 50 yr and have no “warning signs” are subjected to a nonendoscopic test for H. pylori. Those with evidence of infection are treated with a course of therapy directed at H. pylori. Recent studies suggest that this strat- egy reduces endoscopy workload without adversely affect- ing clinical outcomes (3, 4). With few exceptions, because of cost and convenience for the patient, nonendoscopic tests are also favored over endoscopic tests as a means of con- firming H. pylori eradication. The nonendoscopic tests for H. pylori can be split into those that identify an antibody response to this infection and those that identify active infection (“active tests”). Tests that identify active infection include the nonendoscopic urease tests [ 13 C and 14 C-urea breath tests (UBT) and 13 C-urea blood test] and the stool antigen test. Tests that identify active H. pylori infection have consistently been found to have sensitivity and specificity exceeding 90% (5, 6). A number of factors have been found to affect the accu- racy of active testing. The recent use of antibiotics or bis- muth-containing compounds can lead to false-negative (FN) test results (7). Use of a proton pump inhibitor (PPI) before the UBT has also been shown to cause FN results in up to 40% of patients (8 –10). For this reason, it is currently recommended that PPIs be withheld for 1 to 2 wk before the UBT. Unfortunately, this recommendation is impractical for patients with acid-mediated disorders who often suffer with significant symptoms when their PPI is withheld. In the current study, we attempted to confirm that PPIs decrease the sensitivity of the UBT. Previous work (9, 11) has suggested that PPIs induce FN UBT results by a pH- dependent mechanism. To test this hypothesis, we investi- gated whether the iatrogenic manipulation of intragastric pH, at the time of urea ingestion, can reduce the likelihood of FN results in patients taking a PPI. Part of this work was presented at Digestive Diseases Week, San Diego, Califor- nia, May, 2000. THE AMERICAN JOURNAL OF GASTROENTEROLOGY Vol. 96, No. 4, 2001 © 2001 by Am. Coll. of Gastroenterology ISSN 0002-9270/01/$20.00 Published by Elsevier Science Inc. PII S0002-9270(01)02250-X