Determining Factors of Aerosol Deposition for Four pMDI-Spacer Combinations in an Infant Upper Airway Model

Abstract

The aim of this study was to measure and compare the influence of tidal volume (Vt) respiratory rate (RR) and pMDI/spacer combination on aerosol deposition of 4 pMDI/spacer combinations, which are used for infants. An anatomically correct upper airway model of a 9-month-old infant was connected to a breathing simulator. Sinusoidal breathing patterns were simulated with; duty cycle T_i/T_tot = 0.42, Vt: 25, 50, 75, 100, 150, 200 ml (RR: 30 breaths/min); and RR: 20, 30, 42, 60, 78 breaths/min (Vt: 100 mL). pMDI/Spacers tested were: budesonide 200 μg/Nebuchamber^®, fluticasone 125 μg/Babyhaler^® and both budesonide and fluticasone with Aerochamber^®. Plastic spacers were detergent coated to reduce electrostatic charge. Spacer-output and lung dose were measured by a filter positioned between spacer and facemask or between model and breathing simulator. Particle size distribution of lung dose was assessed with an impactor during simulated breathing. Spacer-output was significantly positively correlated with Vt for all pMDI/spacers (all R > 0.77, p < 0.001), but not correlated with RR. Lung doses initially increased from Vt = 25 to 50 mL (Nebuchamber, Aerochamber) or to 100 mL (Babyhaler) and then decreased, with increasing Vt and RR (R: -0.98 to -0.82, p < 0.001). Lung doses of fluticasone were 1.5-6-fold higher compared with budesonide, irrespective of spacer type (p < 0.001). MMAD decreased with increasing Vt and RR. Dose to the lungs of particles <2.1 μm was independent of Vt and RR. Lung dose decreases with increasing inspiratory flow (increasing Vt or RR) by increasing impaction of coarse particles in the upper airways. Deposition of particles <2.1 μm is relatively flow independent. When electrostatic charge of spacers is reduced, lung dose is pMDI dependent and spacer independent.