The13C-urea breath test provides accurate, noninvasive diagnosis of active Helicobacter pylori infection and can document posttherapy cure. This study evaluated point-of-care testing with onsite sample analysis with the use of a desktop infrared spectrophotometer. Ambulatory patients (N = 320) underwent 13C-urea breath testing, and breath samples were analyzed immediately by clinic staff with no prior breath testing experience. Duplicate samples were sent to a reference laboratory, and the results of both methods were compared. Point-of-care testing was simple, with an overall agreement of 99.1%. Accurate near-patient 13C-urea breath testing is now practical in the primary care setting even when done by inexperienced personnel.
Helicobacter pylori infection is etiologically associated with chronic gastritis, peptic ulcer disease, and gastric cancer.1-5Helicobacter pylori infection is also a consideration in the evaluation of uninvestigated or undifferentiated dyspepsia.4-7 The steps in the management of H pylori infection include diagnosis, choice of appropriate therapy, and confirmation of cure.4,5,8 Diagnosis and confirmation of cure require diagnostic testing, and the recent consensus has been in the direction of noninvasive testing.4,5
The urea breath test (UBT) is generally considered the clinical, gold standard, noninvasive test for detection of active H pylori infection.9 The intragastric hydrolysis of orally administered urea by H pylori urease produces a change in the isotopic ratio (13CO2/12CO2) in the breath.10 The 13C-UBT has been approved by the US Food and Drug Administration for pre- and posttherapy testing.11,12
Recently the 13C-UBT has been shortened and simplified by the use of a citric acid test meal and elimination of the requirement of a 4-hour fast.13 Use of infrared mass spectrophotometry for measuring 13CO2 enrichment in breath samples makes it theoretically possible to do office-based breath testing with onsite analysis.14-16 Infrared spectrophotometry has been shown in comparative studies to be an accurate method for assessing 13CO2 enrichment in breath.17-19 No comparative studies of the 2 analytical methods have been done in the United States.
This study examined the utility of UBT testing by comparing infrared spectrophotometry with traditional gas isotope ratio mass spectrometry in the primary care environment. Our hypothesis was that the results obtained from the primary care clinics would be as accurate as those obtained from the commercial laboratory or the more experienced hospital-based clinical laboratory.
Methods
This was a multicenter, prospective study designed to compare a new infrared spectrophotometer (UBiTIR300, Otsuka Pharmaceuticals, Tokyo, Japan) for measuring 13CO2 enrichment in breath with gas isotope ratio mass spectrometry (ABCA, Europa Scientific, Cheshire, UK). Subjects were recruited at the offices or clinics of 4 physicians’ including an indigent care primary care clinic, a hospital-based gastroenterology clinic, a private practice internal medicine office, an academic family medicine clinic, and a tertiary care clinical laboratory site. The study was done between July and September 2001. Consecutive patients were enrolled in the study if they expressed interest in participating and met the inclusion and exclusion criteria. Each site was provided with an infrared spectrophotometer, a breath gas transfer device, and commercially available UBT breath test collection kits (Meretek Diagnostics, Nashville, TN). Each kit contained a 13C-urea solution (125 mg in 75 mL of water), test meal pudding, and a specimen return box containing 4 bar-coded, evacuated 10-mL sample tubes. Before enrollment, all study personnel received approximately 1 hour of training in the performance of the test and use of the equipment.
Study procedures
Subjects included in the study were medically stable, ambulatory patients between 18 and 75 years old who were asymptomatic or experiencing dyspepsia. Potential subjects were excluded from study participation if they took bismuth preparations, antibiotics (ie, amoxicillin, tetracycline, metronidazole, clarithromycin, or azithromycin) or any anti-ulcer medication in dosages indicated for ulcer disease (ie, proton pump inhibitors, type 2 histamine blockers, or misoprostol) within 2 weeks before the study breath test. Exclusion criteria also included participation in a drug study within 4 weeks, treatment for eradication of H pylori within 4 weeks of the study breath test, or a history of gastric surgery or vagotomy for ulcer disease except simple closure of a gastric perforation.
The protocol was approved by the local Institutional Review Board for Human Studies, and all subjects provided written informed consent.
Testing began with a minimum 4-hour fast from solid food. Breath samples were obtained in disposable, balloonlike, breath collection bags designed for use with the infrared spectrophotometer. One sample was obtained immediately before ingestion of the 13C-urea test solution, and the second was collected 30 minutes after substrate ingestion. Paired sample aliquots were taken for separate analyses. Results from local infrared instruments were blinded to the central laboratory.