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Editor,—We read with great interest the paper by McColl and colleagues (Gut1997;40:302–6) reporting the usefulness of the non-invasive Helicobacter pylori 14C-urea breath test (14C-UBT) in predicting underlying ulcer disease in patients with dyspepsia. By administering 0.4 MBq 14C-urea after the test meal, the cut off values calculated by the authors at 20 minutes seem to be very high—namely, above 40 kg% dose/mmol CO2 for H pylori positive and less than 20 kg% dose/mmol CO2for H pylori negative patients. The values between 20 to 40 are suggested to be equivocal. The authors have not given the basis for obtaining these cut off values. We have used the14C-UBT routinely since 1990 and so far have performed this test on almost 500 patients using a wide variety of test protocols. Based on our initial data, the cut off value for H pylori positive patients was calculated to be above 0.6% dose/mmol CO2 × kg (body weight) 15 minutes after oral administration of 185 kBq 14C-urea without giving a test meal or cold substrate.1 Similarly, a theoretical value of 0.585% can be obtained at 15 minutes by multiplying the body weight of an average adult human (65 kg) by the cut off value of 0.009% dose/mmol CO2 reported earlier by us and used to confirm eradication of H pylori.2 ,3Raju and others have also reported a cut off value of 0.55% at 20 minutes using 37 kBq 14C-urea after an overnight fast.4 Most recently, a cut off value of 1.0% dose/mmol CO2 × kg at 10 minutes has been reported after administration of 185 kBq of tracer without capsule.5
In view of the literature cited above, the cut off values for the14C-UBT reported by McColl and colleagues seem to be very high and may be the result of a calculation error or technical problem. If these values are taken as a reference by others, analysis of their14C-UBT data may not distinguish accuratelyH pylori infected from non-infected patients.
To minimise decomposition, it is recommended that stock of14C-urea be stored at −20°C in a freeze-dried solid form. Repeated thawing of the aqueous solution of the tracer causes it to decompose. We have found a drastic reduction in the count rate from 213 793 to 5487 dpm in 20 lambda solution when the tracer was thawed more than 25 times over 109 days; the count rate declined to almost 50% of the original—namely, from 323 000 to 156 499 dpm, when a different solution of tracer was thawed nine times over 112 days. Therefore, ideally the standard should always be prepared from the same stock solution which is administered to the patients. It is likely that the high cut off values obtained by McColl and colleagues resulted from the preparation of standard taken from stock solution which might have been thawed repeatedly, whereas the tracer dose administered to the patients was thawed once or twice only.
As the 14C-UBT is a simple, quick, non- traumatic, highly reliable, and cost effective test, it is used for screening, follow up, and for epidemiological purposes. Different authors have reported different cut off values with variable units depending on the test protocols they have followed, and the results are also expressed in different units.6 To avoid unnecessary confusion in the interpretation of 14C-UBT data, now there is an urgent need for a standard test protocol.
Editor,—Our 20 minute breath test result is in fact expressed in terms of 100 × kg% dose/mmol CO2, but the factor of “100” was omitted in error in the original publication. This explains why our results are much greater than those stated by Pathak and colleagues. The basis for our cut off values as presented in the paper is to be found in an early publication1-1 but in light of further experience with the breath test, it is now our practice to take a result of >30 as positive.1-2 This corresponds to a cut off value of 0.3 in the units used by Pathak and colleagues. The sensitivity and specificity in the determination ofHelicobacter pylori status with this cut off value are 98% and 100% respectively.1-2
We agree with Pathak and colleagues regarding the desirability of standardising the test protocol. In addition to the list of variables they have detailed, which influence the test result, there is the matter of assaying the 14C content of the test sample. If adequate correction is not made for luminescence, this can lead to a falsely raised result, a problem which could be significant with test doses at the lower end of the reported activity range.
The question of preparation, storage and stability of the14C-urea is interesting. Several different approaches have been published—the test dose may be produced in capsule form,1-3 stored at −20°C and thawed just before use,1-4 sterilised and stored at 2–4°C,1-5 or withdrawn, just before use, from a stock solution stored at 2–4°C.1-6 In some cases the main concern has been to ensure that test doses are sterilised before storage, thus preventing any decomposition by urease producing bacteria.1-7 Analysis of the test dose of 14C urea after several weeks1-8 or six months’ storage1-4 1-5 has shown no significant deterioration of the product. In our protocol, the original freeze dried 14C-urea is dissolved in sterile water, from which individual test doses are dispensed into screw-capped containers and stored for up to six weeks at 2–4°C. We have not experienced any problems with decomposition of the product. In terms of convenience, use of a screw-capped container to contain the test dose is less convenient than use of a capsule, but more practical than use of a sealed sterile vial or ampoule. We are currently investigating the use of benzyl alcohol as an antimicrobial preservative to allow longer storage of test doses. From the work of Pathak and colleagues it is clearly inadvisable to freeze and thaw a stock solution of14C urea repeatedly.