BREATH TESTS - CONCEPTS, APPLICATIONS AND LIMITATIONS

Breath tests (BT) using stable isotopically labelled substrates seem t o fullfil all the demands and desires for a non-invasive investigation . There are no radiation hazards, substrates are given in tracer amoun ts perorally, breath and urine samples can be collected easily, and te sts can be done repeatedly, thus easily allowing the monitoring of fun ction with time. There are, however, some disadvantages. Any BT has th e same assumption: after intake of the C-13 tracer the substrate is me tabolized to (CO2)-C-13. An increase of (CO2)-C-13 above baseline leve ls is said to reflect the function investigated-in C-13 sucrose studie s, the amount of carbohydrate absorbed; in C-13 aminopyrine BT, the li ver function; in C-13 glucose BT in a diabetic child, the impaired han dling of glucose. However, as only the end product (CO2)-C-13 is measu red, there is no information on all the pools and fluxes the labelled substrate and its metabolites have to pass. At least in inborn errors of metabolism, probably in any disease, one has to assume that these f luxes and pools are substantially changed. Therefore all calculations are weak and finally one has to resort to invasive methods, i.e. drawi ng blood to measure pools and fluxes to allow a correct interpretation of the BT data. Furthermore, changes in the basal exhalation of (CO2) -C-13 during the test will have an impact on the BT calculation. Anoth er problem is that for an exact calculation, the basal metabolic rate (BMR) and the actual endogenous CO2 production in the patient is neede d, which in most instances is unknown. It is not easy to maintain a st able endogenous CO2 production, particularly in younger children who w ill not rest or in neonates and toddlers who may fight against taking breath samples. Taking together these limitations are the reason why B T have not been able to reach the level of routine clinical methods, e specially in the diagnostic work up of impaired liver function or inbo rn errors of metabolism.