Influence of age on C-13-urea breath test results in children

Background: The C-13-urea breath test for diagnosis of Helicobacter pylori infection has not been validated in infants and young children. The influen ce of age on the test results was studied by conventional validation agains t invasive methods and by mathematical estimation in a large pediatric popu lation. Methods: The breath test was performed in 1499 children aged 2 months to 18 years. After a fasting period of 4 hours or more, 75 mg C-13-urea was inge sted with cold apple juice, breath samples were taken at baseline and at 15 and 30 minutes. The distribution of the natural logarithms of the a-over b aseline (DOB) values were calculated, and the optimal cutoff values between positive and negative test results and gray zones with a risk of misclassi fication more than 10% were determined for both time points. Tn a subgroup of 149 children results of the: breath test were compared with concordant r esults of histology and rapid urease test; 53 of them were less than 6 year s of age. Results: Logarithmic results of 1499 breath tests revealed two normally dis tributed subgroups with minimal overlap. The calculated optimal cutoff valu es were 4.7 parts per thousand at 15 minutes and 5.0 parts per thousand at 30 minutes. At 30 minutes, only 2.6% of all results were in the calculated gray zone (2.6-6.5 parts per thousand). Age was negatively correlated to DO E values of both negative (r = -0.223) and positive results (r = -0.291; P < 0.001). Breath test-negative and -positive children 6 or less years of ag e had significantly higher mean DOE values (P < 0.02) and a larger proporti on of results within the gray zone than older children. Compared with biops y-based results, the least discrepancies occurred at a cutoff of 5.0 parts per thousand: 0 of 61 infected (sensitivity 100%) and 6 of 88 noninfected c hildren. Because five of the false-positive results were obtained in childr en less than 6 years of age, specificity and positive predictive values wer e lower in this age group than in older patients (88.1% vs. 97.8% and 68.8% us. 98.0%, respectively). Conclusions: Under the applied conditions, the C-13-urea breath test shows an excellent separation between positive and negative results. Because of s ome overlap and a strong age effect, definition of a gray zone appears more meaningful than a threshold value. Because infants and young children have a high risk for false-positive breath test results, the values for cutoff and gray zones may have to be adapted. Further validation studies against i nvasive methods are warranted in this age group.