Orally Inhaled Drug Particle Transport in Computerized Models of Laryngotracheal Stenosis

Abstract

Objective Adjuvant management for laryngotracheal stenosis (LTS) may involve inhaled corticosteroids, but metered dose inhalers are designed for pulmonary drug delivery. Comprehensive analyses of drug particle deposition efficiency for orally inhaled corticosteroids in the stenosis of LTS subjects are lacking. Study Design Descriptive research. Setting Academic medical center. Methods Anatomically realistic 3-dimensional reconstructions of the upper airway were created from computed tomography images of 4 LTS subjects—2 subglottic stenosis and 2 tracheal stenosis subjects. Computational fluid dynamics modeling was used to simulate airflow and drug particle transport in each airway. Three inhalation pressures were simulated, 10 Pa, 25 Pa, and 40 Pa. Drug particle transport was simulated for 100 to 950 nanoparticles and 1 to 50 micron-particles. Particles were released into the airway to mimic varying inhaler conditions with and without a spacer chamber. Results Based on smallest to largest cross-sectional area ratio, the laryngotracheal stenotic segment shrunk by 57% and 47%, respectively, for subglottic stenosis models and by 53% for both tracheal stenosis models. Airflow resistance at the stenotic segment was lower in subglottic stenosis models than in tracheal stenosis models: 0.001 to 0.011 Pa.s/mL vs 0.024 to 0.082 Pa.s/mL. Drug depositions for micron-particles and nanoparticles at stenosis were 0.06% to 2.48% and 0.10% to 2.60% for subglottic stenosis and tracheal stenosis models, respectively. Particle sizes with highest stenotic deposition were 6 to 20 µm for subglottic stenosis models and 1 to 10 µm for tracheal stenosis models. Conclusion This study suggests that at most, 2.60% of inhaled drug particles deposit at the stenosis. Particle size ranges with highest stenotic deposition may not represent typical sizes emitted by inhalers.

Comparison of Inhaled Drug Delivery in Patients With One‐ and Two‐level Laryngotracheal Stenosis

“…These findings agree with those in Frank-Ito and Cohen looking at one level of stenosis. 39 On average, smaller particles were deposited at higher rates than larger particles for both MDI and DPI simulations. However, the three cases where a small number of particles over 15 μm were deposited while using DPIs.…”

“…These have been evaluated in other studies investigating a variety of conditions. 38,39,65,66 We aim to add these variables to the simulations reported in this study and incorporate them into future findings and recommendations on this topic.…”

“…Previous works by our team have investigated the impact of one-level stenosis on respiration 38 and stenotic drug delivery. 39 In the latter study, CFD simulations of orally inhaled drug particle transport in four patients with LTS at three inhalation pressures were performed; results suggest that the best particle sizes with the highest stenotic deposition may not represent typical particle sizes emitted by MDIs and DPIs.…”

An Updated Review of Subglottic Stenosis: Etiology, Evaluation, and Management

“…In a small prospective randomized controlled trial (n = 14), the use of ICS in LTS after balloon dilation showed no short-term benefits of treatment [94]. These findings may be explained by a computational analysis using 3-dimensional larynx models that suggests in ideal conditions, only 2.48% of inhaled drug particles may deposit at the site of stenosis [95]. The role of systemic corticosteroids has been assessed prospectively in a randomized placebo-controlled trial for patients with iatrogenic tracheal stenosis after ED, which demonstrated no significant difference in mean SFI Fig.…”

In Silico Quantification of Intersubject Variability on Aerosol Deposition in the Oral Airway

“…To ensure numerically accurate flow simulation results, the Shear-Stress Transport k -ω turbulent model (SST k -ω) was employed to simulate the inspiratory and expiratory airflow for fast-breathing conditions (45 L/min) [ 27 ]. The turbulence length scale was considered 0.001 m, and turbulent intensity was assumed to be 5% at the inlet and outlet [ 28 , 29 ].…”