Particle deposition in the pulmonary region of the human lung: Multiple breath aerosol transport and deposition

Abstract

Comprehensive knowledge of aerosol deposition in the lung during multiple breathing cycles is essential to understanding the long term adverse effects of environmental particulate pollution as well as various therapeutic strategies for aerosolized drug delivery. In this work, a simple semi-empirical model for whole lung aerosol bolus dispersion and deposition developed in an accompanying study [Park, S.S. and Wexler, A.S., 2007. Particle deposition in the pulmonary region of the human lung: A semi-empirical model of single breath transport and deposition. Journal of Aerosol Science 38(2), 228–245] was used to estimate regional particulate dosimetry during multiple breaths. To further validate the transport and deposition model of Park and Wexler [2007. Particle deposition in the pulmonary region of the human lung: A semi-empirical model of single breath transport and deposition. Journal of Aerosol Science 38(2), 228–245], the washin and washout experiments of Davies and coworkers were simulated; predictions compared well to observations. Typical models of pulmonary particle deposition simulated transport to these distal airways by a flow-through approximation where particle-laden air is assumed to flow into the airways and out the alveoli, but resting tidal volumes do not transport particles to the distal pulmonary airways in a single breath. By simulating tidal transport and deposition over a series of breath, we find that the concentration of retained particles as a function of lung depth increases with each tidal cycle and these particles penetrate deeper with succeeding breaths. The retained particle concentration increases more slowly with each breath, so that after the 8th breath, the concentration distribution within the lung attains a steady state. Comparison with observed data and previous model predictions is made in terms of total and generational deposition fractions at steady state. After accounting for the retained fractions, the total predicted deposition fraction was similar to the experimental data while other previous model predictions underestimated it. Predicted deposition fraction per generation showed similar patterns to other model simulations yet higher deposition fractions in the more proximal pulmonary regions. This is a result of the enhanced alveolar deposition in the first half of the acinar generations due to alveoli expansion and contraction.