In Silico Quantification of Intersubject Variability on Aerosol Deposition in the Oral Airway

The extrathoracic oral airway is not only a major mechanical barrier for pharmaceutical aerosols to reach the lung but also a major source of variability in lung deposition. Using computational fluid dynamics, deposition of 1-30 mu m particles was predicted in 11 CT-based models of the oral airways of adults. Simulations were performed for mouth breathing during both inspiration and expiration at two steady-state flow rates representative of resting/nebulizer use (18 L/min) and of dry powder inhaler (DPI) use (45 L/min). Consistent with previous in vitro studies, there was a large intersubject variability in oral deposition. For an optimal size distribution of 1-5 mu m for pharmaceutical aerosols, our data suggest that >75% of the inhaled aerosol is delivered to the intrathoracic lungs in most subjects when using a nebulizer but only in about half the subjects when using a DPI. There was no significant difference in oral deposition efficiency between inspiration and expiration, unlike subregional deposition, which shows significantly different patterns between the two breathing phases. These results highlight the need for incorporating a morphological variation of the upper airway in predictive models of aerosol deposition for accurate predictions of particle dosimetry in the intrathoracic region of the lung.

Automated summary

The extrathoracic oral airway acts as a barrier for pharmaceutical aerosols and introduces variability in lung deposition. Computational fluid dynamics was used to predict deposition of 1-30 μm particles in CT-based models of adult oral airways. Results showed large intersubject variability in oral deposition, with nebulizers delivering >75% of inhaled aerosol to intrathoracic lungs in most subjects compared to only about half with DPI use. Oral deposition efficiency did not differ significantly between inspiration and expiration, but subregional deposition showed different patterns between the two breathing phases. Incorporating upper airway morphological variation is crucial for accurate predictions of aerosol deposition in the lung.