Experimental and computational study of pMDI aerosol delivery in mucus-coated pediatric airways: Effects of inhalation flow and actuation timing.

This study investigates airflow and aerosol deposition in a pediatric mouth-throat (MT) airway model by integrating a cystic fibrosis (CF) inhalation profile, pressurized metered-dose inhaler (pMDI) actuation timing, and an artificial mucus layer to improve understanding of aerosol drug delivery mechanisms. A computed tomography-derived pediatric MT airway model was three-dimensionally printed and coated with artificial pulmonary mucus, establishing a physiologically relevant baseline to assess the effects of a non-Newtonian, shear-thinning mucus layer on drug deposition. The geometry was subsequently integrated into a Next Generation Impactor (NGI) for experimental validation of the computational fluid dynamics framework. The Eulerian wall film (EWF) approach was employed to model the mucus layer, while large-eddy simulation (LES) and discrete-phase modeling (DPM) were used to analyze airflow and particle transport, respectively. Results indicate that inhalation flow rate is the primary determinant of deposition efficiency, with Morris sensitivity analysis showing a strong correlation (rₛ = 0.81). Higher inhalation flow rates increased wall shear stress, thereby enhancing shear-driven particle transport. The presence of shear-thinning mucus modified flow structures by altering secondary flow patterns, inducing asymmetric swirling, and increasing the minimum particle size exiting the trachea by 60.2% (from 0.491 to 0.789 µm) compared with Newtonian mucus. Actuation timing also played a secondary influence on regional deposition, with synchronized pMDI actuation achieving the highest delivery efficiency (approximately 46%) due to improved aerosol entrainment during the acceleration phase of the CF inhalation profile.