Microscopic modeling of NO and S-nitrosoglutathione kinetics and transport in human airways

Nitric oxide (NO) appears in the exhaled breath and is elevated in inflammatory diseases. We developed a steady-state mathematical model of the bronchial mucosa for normal small and large airways to understand NO and S-nitrosoglutathione (GSNO) kinetics and transport using data from the existing literature. Our model predicts that mean steady-state NO and GSNO concentrations for large airways (generation 1) are 2.68 nM and 113 pM, respectively, in the epithelial cells and 0.11 nM (approximately 66 ppb) and 507 nM in the mucus. For small airways (generation 15), the mean concentrations of NO and GSNO, respectively, are 0.26 nM and 21 pM in the epithelial cells and 0.02 nM (approximately 12 ppb) and 132 nM in the mucus. The concentrations in the mucus compare favorably to experimentally measured values. We conclude that 1) the majority of free NO in the mucus, and thus exhaled NO, is due to diffusion of free NO from the epithelial cell and 2) the heterogeneous airway contribution to exhaled NO is due to heterogeneous airway geometries, such as epithelium and mucus thickness.