Single-exhalation profiles of NO and CO2in humans: effect of dynamically changing flow rate

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Abstract
Endogenous production of nitric oxide (NO) in the human lungs has many important pathophysiological roles and can be detected in the exhaled breath. An understanding of the factors that dictate the shape of the NO exhalation profile is fundamental to our understanding of normal and diseased lung function. We collected single-exhalation profiles of NO and CO2 from normal human subjects after inhalation of ambient air (∼15 parts/billion) and examined the effect of a 15-s breath hold and exhalation flow rate (V˙E) on the following features of the NO profile:1) series dead space,2) average concentration in phase III with respect to time and volume,3) normalized slope of phase III with respect to time and volume, and4) elimination rate at end exhalation. The dead space is ∼50% smaller for NO than for CO2 and is substantially reduced after a breath hold. The concentration of exhaled NO is inversely related to V˙E, but the average NO concentration with respect to time has a stronger inverse relationship than that with respect to volume. The normalized slope of phase III NO with respect to time and that with respect to volume are negative at a constantV˙E but can be made to change signs if the flow rate continuously decreases during the exhalation. In addition, NO elimination at end exhalation vs.V˙E produces a nonzero intercept and slope that are subject dependent and can be used to quantitate the relative contribution of the airways and the alveoli to exhaled NO. We conclude that exhaled NO has an airway and an alveolar source.