Dry powder inhaler deposition in the larynx and the risk of steroid inhaler laryngitis: A computational fluid dynamics study

Abstract

Dry Powder Inhalers (DPIs) are a mainstay in the treatment of obstructive respiratory diseases, including asthma and chronic obstructive pulmonary disease (COPD). Deposition of inhaled corticosteroids in the larynx elicits local side effects, potentially leading to steroid inhaler laryngitis. The objective of this study was to estimate the dose of DPIs that are deposited in the larynx relative to other regions of the respiratory tract using computational fluid dynamics (CFD). An anatomically accurate model of the airways (mouth to main bronchi) was constructed based on medical imaging of a healthy adult. Respiratory airflow and particle transport were simulated for constant inhalation rates of 30, 45, and 60 L/min. Two turbulence models were compared, namely the large eddy simulation (LES) and the $k-\omega SST$ models. DPIs were assumed to generate an aerosol cloud with a log-normal particle size distribution characterized by the mass median aerodynamic diameter ($d_{50}$) and geometric standard deviation (${\sigma }_g$). We compared two commercial DPIs, namely DPI 1 had a large particle size ($d_{50}$ = 50 μm, ${\sigma }_g=2.55$) and DPI 2 had a small particle size ($d_{50}$ = 2 μm, ${\sigma }_g=1.99$). The laryngeal dose was 1.6-to-3.8-fold higher than the bronchial dose for DPI 1, while the laryngeal and bronchial doses (units of mass per unit surface area) were similar for DPI 2 for both turbulence models and all inhalation rates. The choice of turbulence model had little impact on the total extrathoracic deposition, but a significant impact on regional doses, with the LES model predicting higher larynx-to-bronchi relative doses than the $k-\omega$ model. Our prediction that the larynx is a hotspot for DPI deposition is consistent with the observation of laryngeal side effects in DPI users. Importantly, our simulations suggest that DPIs with larger particles ($d_{50}$ = 50 μm) may increase the risk of steroid inhaler laryngitis.