Simultaneous measurement of nitric oxide production by conducting and alveolar airways of humans

Abstract

Human airways produce nitric oxide (NO), and exhaled NO increases as expiratory flow rates fall. We show that mixing during exhalation between the NO produced by the lower, alveolar airways (V̇L(NO)) and the upper conducting airways (V̇U(NO)) explains this phenomenon and permits measurement of V̇L(NO), V̇U(NO), and the NO diffusing capacity of the conducting airways (DU(NO)). After breath holding for 10-15 s the partial pressure of alveolar NO (PA) becomes constant, and during a subsequent exhalation at a constant expiratory flow rate the alveoli will deliver a stable amount of NO to the conducting airways. The conducting airways secrete NO into the lumen (V̇U(NO)), which mixes with PA during exhalation, resulting in the observed expiratory concentration of NO (PE). At fast exhalations, PA makes a large contribution to PE, and, at slow exhalations, NO from the conducting airways predominates. Simple equations describing this mixing, combined with measurements of PE at several different expiratory flow rates, permit calculation of PA, V̇U(NO), and DU(NO). V̇L(NO) is the product of PA and the alveolar airway diffusion capacity for NO. In seven normal subjects, PA = 1.6 ± 0.7 x 10-6 (SD) Torr, V̇L(NO) = 0.19 ± 0.07 μl/min, V̇U(NO) = 0.08 ± 0.05 μl/min, and DU(NO) = 0.4 ± 0.4 ml · min-1 · Torr-1. These quantitative measurements of V̇L(NO) and V̇U(NO) are suitable for exploring alterations in NO production at these sites by diseases and physiological stresses.