Axial distribution heterogeneity of nitric oxide airway production in healthy adults

Abstract

Model simulations of nitric oxide (NO) transport considering molecular diffusion showed that the total bronchial NO production needed to reproduce a given exhaled value is deeply influenced by its axial distribution. Experimental data obtained by fibroscopy were available about proximal airway contribution (Silkoff PE, McClean PA, Caramori M, Slutsky AS. Zamel N. Respir Physiol 113: 33–38, 1998), and recent experiments using heliox instead of air gave insight on the peripheral airway production (Shin HW, Condorelli P, Rose-Gottron CM, Cooper DM, George SC. J Appl Physiol 97: 874–882, 2004; Kerckx Y, Michils A, Van Muylem A. J Appl Physiol 104: 918–924, 2008). This theoretical work aimed at obtaining a realistic distribution of NO production in healthy adults by meeting both proximal and peripheral experimental constraints. To achieve this, a model considering axial diffusion with geometrical boundaries derived from Weibel's morphometrical data was divided into serial compartments, each characterized by its axial boundaries and its part of bronchial NO production. A four-compartment model was able to meet both criteria. Two compartments were found to share all the NO production: one proximal ( generations 0 and 1; 15–25% of the NO production) and one inside the acinus (proximal limit, generations 14–16; distal limit, generations 16 and 17; 75–85% of the NO production). Remarkably, this finding implies a quasi nil production in the main part of the conducting airways and in the acinar airways distal to generation 17. Given the chosen experimental outcomes and reliant on their accuracy, this very inhomogeneous distribution is likely the more realistic one that may be achieved with a “one-trumpet”-shaped model. Refinement should come from a more realistic description of the acinus structure.