A clinically applicable method for assessing lung permeability in the non-steady-state

Abstract

A clinically applicable method for assessing the permeability of the alveolar-capillary barrier under non-steady-state conditions has been developed. Following deposition of a suitable tracer in the lungs, its rate of entry into the blood can be measured using blood samples alone, without the necessity for external monitoring. A second reference tracer must be infused in order to compensate for renal excretion and for redistribution of tracer in the extravascular space. Tracers of any convenient molecular weight and physical properties can be used, either unlabelled, or labelled with stable or radioactive isotopes. The method was examined by computer simulation in order to assess its sensitivity to measurement “noise”. In contrast to other non-steady-state tracer techniques, it is markedly less sensitive to experimental uncertainty, and measurements to an accuracy of 1–2% (coefficient of variation) should suffice for most purposes. The method was also validated by in vivo experiment in the pig, using a constant intravenous infusion of 51 Cr-EDTA as the reference tracer and a variable intravenous infusion of 99m Tc-DTPA to simulate entry from the alveoli. Good agreement was obtained between the calculated entry rate of the 99m Tc-DTPA and the true entry rate known from the infusion pump rate.