Factors Influencing Trans-Nasal Aerosol Drug Delivery: Mouth Status, Exhaled Humidification and Simulated Models

Abstract

Background: Aerosol delivery in-line with high-flow nasal cannula (HFNC) has been increasingly utilized. However, most of the studies were conducted using models with mouth closed, which might not reflect the real-life scenario. Thus, we aimed to compare different simulated models, varying mouth status, and with/without exhaled humidity to explore factors influencing the inhaled dose.

Methods: A 3D-printed adult nose-mouth-throat (NMT) model was compared with an adult training manikin for intubation. A collecting filter was connected between the trachea and breath simulator, set to adult breathing parameters of tidal volume [V_T] 470 mL, frequency 21 breaths/min, and inspiratory time [T_I] 1.1 s. The mouth was sealed with tape to simulate closed-mouth breathing and removed for open-mouth breathing. A humidifier was placed between the collecting filter and the model lung to simulate exhaled humidity. Albuterol (2.5 mg/3 mL) was delivered via a vibrating mesh nebulizer (VMN) positioned at the humidifier’s outlet in the HFNC device (Airvo2), with flows set at 15 L/min and 45 L/min. Each experiment was repeated 5 times. The drug was eluted from the collection filter after each run and assayed with ultraviolet spectrophotometry (276 nm).

Results: The NMT model had higher inhaled dose than the adult manikin in all settings (all P < .05), except for the open mouth-breathing at 15 L/min (21.1 ± 0.6 vs 24.4 ± 1.3, P = .001) (Table 1). At 45 L/min, there was no significant difference between open-mouth breathing and closed-mouth breathing in both models. However, at 15 L/min, closed-mouth breathing of NMT model had a higher inhaled dose than open-mouth breathing (24.7 ± 0.4 vs 21.1 ± 0.6, P = .008), while in the adult manikin, closed-mouth breathing had a lower inhaled dose than open-mouth breathing (18.9 ± 1.4 vs 24.4 ± 1.3%, P = .008). In the adult manikin during open-mouth breathing, the inhaled dose with exhaled humidity was higher than without exhaled humidity in both flow settings (all P < .05) (Figure 1).

Conclusions: Trans-nasal pulmonary aerosol delivery can be affected by simulating model, mouth status, and exhaled humidity.

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Figure 1. Aerosol delivery via high-flow nasal cannula with versus without exhaled humidity in adult manikin.