A new role for the exhaled nitric oxide as a functional marker of peripheral airway caliber changes: a theoretical study

Although considered as an inflammation marker, exhaled nitric oxide (FENO) was shown to be sensitive to airway caliber changes to such an extent that it might be considered as a marker of them. It is thus important to understand how these changes and their localization mechanically affect the total NO flux penetrating the airway lumen ( JawNO), and hence FENO, independently from any inflammatory status change. In this work, a new model was used. It simulates NO production, consumption, and diffusion inside the airway epithelium, NO excretion from the epithelial wall into the airway lumen and, finally, its axial transport by diffusion and convection in the airway lumen. This model may also consider the possible presence of a fluid layer coating the epithelial wall. Simulations were performed. They show the great sensitivity of JawNO to peripheral airway caliber changes. Moreover, FENO shows distinct behaviors, depending on the location of the caliber change. Considering a bronchodilation, absence of FENO change was associated with dilation of central airways, FENO increase with dilation down to pre-acinar small airways, and FENO decrease with intra-acinar dilation due to the amplification of the back diffusion flux. The presence of a fluid layer was also shown to play a significant role in FENO changes. Altogether, the present work theoretically supports that specific FENO changes in acute situations are linked to specifically located airway caliber changes in the lung periphery. This opens the way for a new role for FENO as a functional marker of peripheral airway caliber change. NEW & NOTEWORTHY Using a new model of nitric oxide production and transport, allowing realistic simulation of airway caliber change, the present work theoretically supports that specific changes of the molar fraction of nitric oxide in the exhaled air, occurring without any change in the inflammatory status, are linked to specifically located airway caliber changes in the lung periphery. This opens the way for a new role for FENO as a functional marker of peripheral airway caliber change.