The acinar region of the human lung comprises about 300 million alveoli which are the smallest units of the lung and are responsible for gas exchange between the lung and the blood. The ability of the alveoli to exchange gas is often compromised by the deposition of harmful inhaled particulate matter on the alveolar wall. At the same time, the alveoli can also be exploited as effective delivery sites for inhaled therapeutic aerosols for local and systemic ailments.
In healthy lungs, the expansion/contraction of the alveolar cavity during each breathing cycle is typically synchronized with the oscillating fluid flow in the bronchiole and is known as synchronous ventilation. Synchronous ventilation can be compromised by a variety of lung ailments such as chronic bronchitis or emphysema leading to a condition known as asynchronous ventilation. Although gas transport is governed primarily by diffusion due to the small length scales associated with the acinar region (∼500 μm), the transport and deposition of inhaled aerosol particles is influenced by convective airflow patterns. Therefore, understanding alveolar fluid flow and mixing is a necessary first step towards predicting aerosol transport and deposition in the human acinar region.
In the current work, acinar airflow patterns were measured using a simplified in-vitro alveolar model consisting of a single alveolus located on a bronchiole. The model comprised a transparent elastic 5/6th spherical cap (representing the alveolus) mounted over a circular hole on the side of a rigid circular tube (representing the bronchiole). Our model alveolus is capable of expanding and contracting in-phase and out-of-phase with the oscillatory flow through the tube thereby simulating synchronous and asynchronous ventilation, respectively. Realistic breathing conditions were achieved by exercising the model at physiologically relevant Reynolds and Womersley numbers. Particle image velocimetry was used to measure the resulting flow patterns. The particle maps were used to calculate the transport and deposition statistics of massless and finite-size particles under the influence of flow advection and/or gravity. Velocity measurements and particle transport calculations were divided into three categories.
First, we focused on synchronous ventilation wherein the experimental conditions were matched with tidal breathing in healthy humans. Our results show that the alveolar wall motion enhances mixing between the bronchiole and alveolar fluid and increases particle transport and deposition on the alveolar wall for all particle sizes. Furthermore, particles ≤ 0.25 μm follow the fluid streamlines quite closely whereas particles ≥ 1 μm cross streamlines and exhibit complex trajectories due to the cumulative effect of flow advection and gravity.
Next, we measured flow patterns and calculated particle trajectories for asynchronous ventilation which is typical of diseased lungs. A range of realistic phase lags between the bronchiole flow oscillation and the alveolar wall oscillation was considered. Particle trajectories were calculated over multiple breathing cycles for massless and finite-size particles of diameter = 1.5 μm. The asynchronous ventilation results show that fluid mixing and particle deposition display a non-monotonic behavior as the phase lag is increased from 0 to π/2; fluid mixing and particle deposition are lowest for 11π/90 and highest for π/2.
Finally, we characterized flow patterns and particle trajectories for a range of physiologically relevant dimensionless parameters and particle size for the case of synchronous ventilation. Our study shows that particles smaller than 0.25 micron follow fluid streamlines without deviation, particles in the range 0.25 μm ≤ dp ≤ 3 μm are transported under the combined influence of convection and gravity, and particles larger than 3 micron sediment rapidly due to gravity. Our parametric study shows that the geometric parameters (β and ΔV/V) primarily affect the velocity magnitudes, and the dynamic parameters (Re and α) distort the flow symmetry in addition to altering the velocity magnitudes. The particle trajectories also display a greater influence of dynamic parameters compared to geometric parameters.
Overall, this work can benefit the research community engaged in the risk assessment of toxicological inhaled aerosols, as well as the pharmaceutical industry, by providing improved insight and understanding of flow patterns and particle transport in the acini. Specifically, the asynchronous ventilation results can contribute to the design of pharmaceutical aerosols with the optimal characteristics and the associated pulmonary drug delivery protocols.