The Laryngoscope · 2022 · 14 citations · 54 references
PharmacyPharmacologyDrug DeliveryPulmonary Drug DeliveryPulmonologyInhalation Drug DeliveryInhaled Medication AdministrationLung DepositionRespiratory MedicineRespiratory System ModelingAerosol Particle DepositionDrug Delivery To The AirwaysDry Powder DepositionDry Powder Inhaler DepositionInhalable Particle DepositionInhalation Aerosol DynamicsMetered-dose Inhaler DepositionPulmonary Drug Transport
OBJECTIVES/HYPOTHESIS: Laryngotracheal stenosis (LTS) is a functionally devastating condition with high respiratory morbidity and mortality. This preliminary study investigates airflow dynamics and stenotic drug delivery in patients with one- and two-level LTS. STUDY DESIGN: A Computational Modeling Restropective Cohort Study. METHODS: Computed tomography scans from seven LTS patients, five with one-level (three subglottic, two tracheal), and two with two-level (glottis + trachea, glottis + subglottis) were used to reconstruct patient-specific three-dimensional upper airway models. Airflow and orally inhaled drug particle transport were simulated using computational fluid dynamics modeling. Drug particle transport was simulated for 1-20 μm particles released into the mouth at velocities of 0 m/s, 1 m/s, 3 m/s, and 10 m/s for metered dose inhaler (MDI) and 0 m/s for dry powder inhaler (DPI) simulations. Airflow resistance and stenotic drug deposition in the patients' airway models were compared. RESULTS: Overall, there was increased airflow resistance at stenotic sites in subjects with two-level versus one-level stenosis (0.136 Pa s/ml vs. 0.069 Pa s/ml averages). Subjects with two-level stenosis had greater particle deposition at sites of stenosis compared to subjects with one-level stenosis (average deposition 2.31% vs. 0.96%). One-level stenosis subjects, as well as one two-level stenosis subject, had the greatest deposition using MDI with a spacer (0 m/s): 2.59% and 4.34%, respectively. The second two-level stenosis subject had the greatest deposition using DPI (3.45%). Maximum deposition across all stenotic subtypes except one-level tracheal stenosis was achieved with particle sizes of 6-10 μm. CONCLUSIONS: Our results suggest that patients with two-level LTS may experience a more constricted laryngotracheal airflow profile compared to patients with one-level LTS, which may enhance overall stenotic drug deposition. LEVEL OF EVIDENCE: NA Laryngoscope, 133:366-374, 2023.
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