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 state 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,alv)) in the alveolar region. We have recently demonstrated that D(NO,alv) is not constant, but increases with alveolar volume (VA) given by the following average relationship: D(NO,alv) =48*VA(2/3) ml/min/mmHg (where VA is expressed in liters, STPD). We investigated the potential impact of a variable D(NO,alv) on exhaled concentration by incorporating the volume dependence into the currently accepted two-compartment model for NO exchange dynamics. Our results suggest that the mechanism underlying the plateau in exhaled concentration is a constant ratio J(max,alv)/D(NO,alv) This constant ratio requires a volume dependence of J(max,alv) similar to D(NO,alv), and is likely due to a decreasing alveolar surface area during exhalation.