Septal destruction enhances chaotic mixing and increases cellular doses of nanoparticles in emphysematous acinus

Abstract

Abstract One hallmark of emphysema is the breakdown of inter-alveolar septal walls in pulmonary acini. How the acinar dosimetry of environmental aerosols varies at different stages of emphysema remains unclear; this is specifically pertinent to users of tobacco products, which is the leading cause of emphysema. The objective of this study is to systematically assess the impacts of septal destruction on the behavior and fate of nanoparticles (1–800 nm) in a pyramid-shaped sub-acinar model consisting of 496 alveoli. Four diseased geometry variants were created by gradually removing the septal walls from the base model. Particle motions within the acinar region were tracked for particles raging 1–800 nm at four emphysema stages using a well-tested Lagrangian tracking model. Both spatial profile and temporal variation of particle deposition were predicted in healthy and diseased sub-acinar geometries on both a total and regional basis. Results show large differences in airflow and particle dynamics among different emphysema stages. Large differences in particle dynamics are also observed among different particle sizes, with one order of magnitude’s variation in the speeds of particles of 1, 10, and 200 nm. The destruction of septal walls also changed the deposition mechanisms, shifting from connective diffusion to chaotic mixing with emphysema progression. The sub-acinar dosimetry became less sensitive to particle size variation with more septal destructions. The lowest retention rate was found at 200–500 nm in the healthy sub-acinar geometry, but at 800 nm in all emphysematous models considered. The acinus-averaged dose for nanoparticles (1–800 nm) increases with aggravating septal destructions, indicating an even higher risk to the acinus at later emphysema stages.