Single-exhalation profiles of NO and CO2 in humans: effect of dynamically changing flow rate

Endogenousproduction of nitric oxide (NO) in the human lungs has many importantpathophysiological roles and can be detected in the exhaled breath. Anunderstanding of the factors that dictate the shape of the NOexhalation profile is fundamental to our understanding of normal anddiseased lung function. We collected single-exhalation profiles of NOand CO₂ from normal human subjectsafter inhalation of ambient air (~15 parts/billion) and examined theeffect of a 15-s breath hold and exhalation flow rate(_E) on thefollowing features of the NO profile:1) series dead space,2) average concentration in phaseIII with respect to time and volume,3) normalized slope of phase IIIwith respect to time and volume, and4) elimination rate at endexhalation. The dead space is ~50% smaller for NO than forCO₂ and is substantially reducedafter a breath hold. The concentration of exhaled NO is inverselyrelated to _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 tovolume are negative at a constant_E but can bemade to change signs if the flow rate continuously decreases during theexhalation. In addition, NO elimination at end exhalation vs._E produces anonzero intercept and slope that are subject dependent and can be usedto quantitate the relative contribution of the airways and the alveolito exhaled NO. We conclude that exhaled NO has an airway and analveolar source.