In Vitro Determination of the Main Effects in the Design of High-Flow Nasal Therapy Systems with Respect to Aerosol Performance

INTRODUCTION: The use of concurrent aerosol delivery during high-flow nasal therapy (HFNT) may be exploited to facilitate the delivery of a variety of prescribed medications for inhalation. Until now, a systematic approach to determine the conditions required to yield an optimal emitted dose has not been reported. The aim of this study was to establish the effects of gas flow rate, input droplet size, and nebulizer position on the amount of aerosol exiting the nasal cannula during HFNT and thus becoming available for inhalation. METHODS: Testing was completed according to a factorial statistical design of experiments (DOE) approach. Emitted dose was characterized with a vibrating mesh nebulizer (Aerogen Solo, Aerogen Ltd) for an adult model of HFNT at three clinically relevant gas flow rates, using three nebulizers producing varying input droplet sizes and placed at two different nebulizer positions. RESULTS: Increasing the gas flow rate significantly lowered the emitted dose, with a dose of 7.10% obtained at 10 LPM, 2.67% at 25 LPM, and 1.30% at 40 LPM (p < 0.0001). There was a significant difference in emitted dose between nebulizers with different input droplet sizes, with increasing input droplet size associated with a reduced emitted dose (6.11% with an input droplet size of 3.22 µm, 2.76% with 4.05 µm, and 2.38% with 4.88 µm, p = 0.0002, Pearson’s r = − 0.2871). In addition, the droplet size exiting the nasal cannula interface was lower than that produced by the aerosol generator for all devices under test. Positioning the nebulizer immediately after the humidification chamber yielded a marginally greater emitted dose (3.79%) than when the nebulizer was placed immediately upstream of the nasal cannula (3.39%). Flow rate, input droplet size, and nebulizer position were at the 0.10 level of significance, indicating that all three factors had significant effects on emitted dose. According to the DOE model, flow rate had the greatest influence on emitted dose, followed by input droplet size and then nebulizer position. CONCLUSION: Our findings indicate that in order to optimize the amount of aerosol exiting the nasal cannula interface during HFNT, it is necessary for gas flow rate to be low and the input droplet size to be small, while the nebulizer should be positioned immediately after the humidification chamber. FUNDING: Aerogen Limited.