A single-breath technique with variable flow rate to characterize nitric oxide exchange dynamics in the lungs

Current techniques to estimate nitric oxide (NO) production and elimination in the lungs are inherently nonspecific or are cumbersome to perform (multiple-breathing maneuvers). We present a new technique capable of estimating key flow-independent parameters characteristic of NO exchange in the lungs: 1) the steady-state alveolar concentration (C_alv,ss), 2) the maximum flux of NO from the airways (J_NO,max), and 3) the diffusing capacity of NO in the airways (D_NO,air). Importantly, the parameters were estimated from a single experimental single-exhalation maneuver that consisted of a preexpiratory breath hold, followed by an exhalation in which the flow rate progressively decreased. The mean values for J_NO,max D_NO,air, and C_alv,ss do not depend on breath-hold time and range from 280-600 pl/s, 3.7-7.1 pl·s^-1·parts per billion (ppb)^-1, and 0.73-2.2 ppb, respectively, in two healthy human subjects. A priori estimates of the parameter confidence intervals demonstrate that a breath hold no longer than 20 s may be adequate and that J_NO,max can be estimated with the smallest uncertainty and D_NO,air with the largest, which is consistent with theoretical predictions. We conclude that our new technique can be used to characterize flow-independent NO exchange parameters from a single experimental single-exhalation breathing maneuver.