Transport and deposition of hygroscopic particles in asthmatic subjects with and without airway narrowing

Abstract

This study numerically investigates the effect of hygroscopicity on transport and deposition of particles in severe asthmatic lungs with distinct airway structures. The study human subjects were selected from two imaging-based severe asthmatic clusters with one characterized by nonconstricted airways and the other by constricted airways in the lower left lobe (LLL). We compared the deposition fractions of sodium chloride (NaCl) particles with a range of aerodynamic diameters (1-8 μm) in cluster archetypes under conditions with and without hygroscopic growth. The temperature and water vapor distributions in the airways were simulated with an airway wall boundary condition that accounts for variable temperature and water vapor evaporation at the interface between the lumen and the airway surface liquid layer. On average, the deposition fraction increased by about 6% due to hygroscopic particle growth in the cluster subjects with constricted airways, while it increased by only about 0.5% in those with nonconstricted airways. The effect of particle growth was most significant for particles with an initial diameter of 2 μm in the cluster subjects with constricted airways. The effect diminished with increasing particle size, especially for particles with an initial diameter larger than 4 μm. This suggests the necessity to differentiate asthmatic subjects by cluster in engineering the aerosol size for tailored treatment. Specifically, the treatment of severe asthmatic subjects who have constricted airways with inhalation aerosols may need submicron-sized hygroscopic particles to compensate for particle growth, if one targets for delivering to the peripheral region. These results could potentially inform the choice of particle size for inhalational drug delivery in a clusterspecific manner.

Longitudinal Imaging-Based Clusters in Former Smokers of the COPD Cohort Associate with Clinical Characteristics: The SubPopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS)

“… 8 In conjunction with computational fluid dynamics (CFD) lung models, the cluster information allows exploring the notion of a cluster-guided approach to predict deposition of inhaled drug aerosols using CFD and improve the efficacy of drug delivery in cluster subjects towards personalized therapeutic decisions. 53 , 54 …”

Modeling of the transport, hygroscopic growth, and deposition of multi-component droplets in a simplified airway with realistic thermal boundary conditions

“…Compared with most of the experimental data points of droplet diameters, the discrepancies between the numerical simulation and the experiments are less than 2% in RH. Very recently, Rajaraman et al (2020) duplicated this model, and used the properties and conditions we proposed to validate the model. Similar model accuracy was achieved.…”

Predicting systemic and pulmonary tissue barrier concentration of orally inhaled drug products

“…A full 24 generation lung model of an adult male human was developed for this study. Unlike previous full lung models,[35, 36] the newly developed model was used to simultaneously simulate (i) flow transport simulations, i.e., inhalation and exhalation simulations and (ii) aerosol transport and deposition simulations, over several breathing cycles. In this section, we will briefly describe the process for: i) extending the Q3D lung which was extracted from the Zygote stereolithography (STL format) to the end of the tracheobronchial limit (i.e., Gen 0-15), and ii) constructing the “sac-trumpet” like control volumes at the end of the tracheobronchial exits to mimic the alveolar region (Gen 16-23) and terminal alveolar sacs (Gen 24).…”