## 3 Results
### Benchmark Surfactant Aerosol Deposition Studies  
The fraction of surfactant deposited on each part of the in vitro set-up after nebulization with the Westmed and Fisher & Paykel NCs is displayed in Table 1. The lung dose was higher with the Fisher & Paykel premature size NCs compared with the Westmed infant NCs. The highest fraction of surfactant was recovered from the PrINT cast in both cases, although more surfactant was recovered from the PrINT cast with the Westmed NCs. Conversely, more surfactant was deposited within the nebulizer and NCs after nebulization using the Fisher & Paykel NCs. In addition, a higher fraction of surfactant was collected in the backup trap placed between the PrINT and the lung dose filter with the Fisher & Paykel NCs, indicating that more surfactant entered the upper airways of the PrINT cast with this type of NCs. The higher lung dose and the greater fraction of surfactant recovered in the backup trap predicted a higher intra-corporeal aerosol deposition with the Fisher & Paykel NCs, which were, therefore, selected for the subsequent in vivo study. Approximately 25-30% of the surfactant filled in the nebulizer could not be recovered and was most probably released to the ambient air as fugitive aerosols through the air leak occurring between the HFNC interface and the PrINT model. In Vivo Effect of Nebullized Surfactant during HFNC with the OptiflowTM System in Surfactant-Depleted Rabbits  
There were no significant differences between groups in the body weight or the number of BALs required to induce respiratory distress (Table 2). \begin{table}
\begin{tabular}{l c c} \hline
**Surfactant Deposition (\%)** & **[PERSON] (Infant Size)** & **Fisher \& Paykel (Premature Size)** \\ \hline PrINT cast & 66.9 \(\pm\) 5.9 & 46.2 \(\pm\) 7.9 \\ \hline Nebullizer + nasal cannula & 5.5 \(\pm\) 0.3 & 18.8 \(\pm\) 4.1 \\ \hline Backup trap & 0.6 \(\pm\) 0.1 & 4.2 \(\pm\) 4.1 \\ \hline Lung dose & 0.5 \(\pm\) 0.45 & 1.8 \(\pm\) 1.9 \\ \hline Surfactant recovered vs. filled & 73.5 \(\pm\) 6.0 & 71.0 \(\pm\) 14.8 \\ \hline \end{tabular}
\end{table} 
Table 1: Surfactant deposition during humidified high-flow nasal cannula (HFNC) at 8 L/min. Figure 2: Pharyngeal pressure measurements during humidified high-flow nasal cannula (HFNC) respiratory support at 8 L/min with different types of commercially available nasal cannulas ( NCs) in spontaneously breathing adult rabbits with induced respiratory distress. The dashed line indicates the reference pharyngeal pressure achieved at a nasal continuous positive airway pressure (CPAP) level of 5 cmH\({}_{2}\)O. No signal of pharyngeal pressure was detected with the Vapothern premature NCs. Three independent pharyngeal pressure measurements were performed for each NC type. Repeated BALs induced severe respiratory distress, producing a dramatic drop in arterial oxygenation and an increase in the PaCO\({}_{2}\). Arterial oxygenation rapidly improved in the animals treated with an intratracheal bolus of 200 mg/kg of surfactant and gradually increased over the follow-up period, reaching baseline values at 180 min (Figure 3A). In contrast, the mean PaO\({}_{2}\) of the animals treated with nebulized surfactant during HFNC did not improve despite receiving a nominal dose of 400 mg/kg. Arterial oxygenation was also low in the HFNC (Control) group, as expected, although a slight increase in the mean PaO\({}_{2}\) could be observed after 150 min of HFNC ventilation. All animals developed hypercarbia after surfactant depletion, which was persistent in all the experimental groups (Figure 3B). However, the animals in the HFNC (Control) group registered a steady increase in the PaCO\({}_{2}\), which reached statistical significance compared to surfactant-treated groups at 150 and 180 min. The mean C\({}_{\rm dyn}\) dropped by over 50% in all groups after surfactant depletion. C\({}_{\rm dyn}\) improved in the animals treated with an intratracheal surfactant bolus, although the mean C\({}_{\rm dyn}\) recovery could not reach baseline values.