Deposition of bolus and continuously inhaled aerosols in rhythmically moving terminal alveoli

Abstract

The particle dynamics in an oscillating alveolus under tidal breathing can be dramatically different from those in a static alveolus. Despite its close relevance to pulmonary drug delivery and health risk from airborne exposure, quantifications of alveolar deposition are scarce due to its inaccessibility to in vivo measurement instruments, tiny size to replicate in vitro, and dynamic wall motions to model. The objective of this study is to introduce a numerical method to quantify alveolar deposition with continuous particle release in a rhythmically oscillating alveolus by integrating the deposition curves for bolus aerosols and use this method to develop correlations applicable in assessing alveolar drug delivery efficiency or dosimetry of inhaled toxicants. An idealized blind-end terminal alveolus model was developed with rhythmically moving alveolar boundary conditions in phase with tidal breathing. The dynamic wall expansion mode and magnitude were based on experimentally measured chest wall motions and tidal volumes. A well-validated Lagrangian tracking model was used to simulate the transport and deposition of inhaled micrometer particles. Large differences were observed between dynamic and static alveoli in particle motion, deposition onset, and final alveolar deposition fraction. Alveolar deposition of bolus aerosols is highly sensitive to breath-holding duration, particle release time, and alveolar dimension. For 1 µm particles, there exists a cut-off release time (zero bolus deposition), which decreases with alveolar size (i.e., 1.0 s in a 0.2-mm-diameter alveolus and 0.56 s in a 0.8-mm-diameter alveolus). The cumulative alveolar deposition was predicted to be 39% for a 0.2-mm-diameter alveolus, 22% for a 0.4-mm-diameter alveolus, and 10% for a 0.8-mm-diameter alveolus. A cumulative alveolar deposition correlation was developed for inhalation delivery with a prescribed period of drug release and the second correlation for the time variation of alveolar deposition of ambient aerosols, both of which captured the relative dependence of the particle release time and alveolar dimension.