Breath tests: concepts, applications and limitations

Abstract

Breath tests (BT) using stable isotopically labelled substrates seem to fullfil all the demands and desires for a non-invasive investigation. There are no radiation hazards, substrates are given in tracer amounts perorally, breath and urine samples can be collected easily, and tests can be done repeatedly, thus easily allowing the monitoring of function with time. There are, however, some disadvantages. Any BT has the same assumption: after intake of the ¹³C tracer the substrate is metabolized to ¹³CO₂. An increase of ¹³CO₂ above baseline levels is said to reflect the function investigated – in ¹³C sucrose studies, the amount of carbohydrate absorbed; in ¹³C aminopyrine BT, the liver function; in ¹³C glucose BT in a diabetic child, the impaired handling of glucose. However, as only the end product ¹³CO₂ is measured, 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 fluxes and pools are substantially changed. Therefore all calculations are weak and finally one has to resort to invasive methods, i.e. drawing blood to measure pools and fluxes to allow a correct interpretation of the BT data. Furthermore, changes in the basal exhalation of ¹³CO₂ during the test will have an impact on the BT calculation. Another problem is that for an exact calculation, the basal metabolic rate (BMR) and the actual endogenous CO₂ production in the patient is needed, which in most instances is unknown. It is not easy to maintain a stable endogenous CO₂ production, particularly in younger children who will not rest or in neonates and toddlers who may fight against taking breath samples. Taking together these limitations are the reason why BT have not been able to reach the level of routine clinical methods, especially in the diagnostic work up of impaired liver function or inborn errors of metabolism.