Impact of volume-dependent alveolar diffusing capacity on exhaled nitric oxide concentration

Exhaled endogenous nitric oxide (NO) holds promise as a potential biomarker of pulmonary inflammation. Previous experimental and theoretical work has concluded that the alveolar concentration approaches a constant steady stat e value at end exhalation due to both a constant maximum flux or release of NO (J(max,alv)) and a constant diffusing capacity (D-NO,D-alv) in the alve olar region. We have recently demonstrated that D-NO,D-alv is not constant, but increases with alveolar volume (V-A) given by the following average re lationship: D-NO,D-alv =48*V-A(2/3) ml/min/mmHg (where V-A is expressed in liters, STPD). We investigated the potential impact of a variable D-NO,D-al v on exhaled concentration by incorporating the volume dependence into the currently accepted two-compartment model for NO exchange dynamics. Our resu lts suggest that the mechanism underlying the plateau in exhaled concentrat ion is a constant ratio J(max,alv)/D-NO,D-alv. This constant ratio requires a volume dependence of J(max,alv) similar to D-NO,D-alv, and is likely due to a decreasing alveolar surface area during exhalation. (C) 2001 Biomedic al Engineering Society.