Background. New aerosol drugs for infants may require more efficient delivery systems, including face masks. Maximizing delivery efficiency requires tight-fitting masks with minimal internal mask volumes, which could cause carbon dioxide (CO2) retention. An RNA-interference-based antiviral for treatment of respiratory syncytial virus in populations that may include young children is designed for aerosol administration. CO2 accumulation within inhalation face masks has not been evaluated. Methods. We simulated airflow and CO2 concentrations accumulating over time within a new facemask designed for infants and young children (PARI SMARTMASK？ Baby). A one-dimensional model was first examined, followed by 3-dimensional unsteady computational fluid dynamics analyses. Normal infant breathing patterns and respiratory distress were simulated. Results. The maximum average modeled CO2 concentration within the mask reached steady state (3.2% and 3% for normal and distressed breathing patterns resp.) after approximately the 5th respiratory cycle. After steady state, the mean CO2 concentration inspired into the nostril was 2.24% and 2.26% for normal and distressed breathing patterns, respectively. Conclusion. The mask is predicted to cause minimal CO2 retention and rebreathing. Infants with normal and distressed breathing should tolerate the mask intermittently delivering aerosols over brief time frames. 1. Introduction New aerosol drugs may require more efficient delivery systems, but devices to safely and effectively deliver aerosols to young children have been insufficiently evaluated. Because very young infants are obligate nose breathers, they cannot receive aerosols via a mouthpiece and therefore require a facemask. Both the contour of the mask [1] and the seal between the mask and the patient’s face affect aerosol delivery. Leakage between the face and the mask reduces the drug delivery to the patient [2, 3] and increases facial deposition [3]. Thus, a relatively tight seal between the mask and the face is favorable to maintain a high-percent delivered dose. However, a tightly sealed mask increases the dead space, as CO2-enriched exhaled breath only partially escapes the mask. Infants have low tidal volumes (~6？mL/kg body weight). Thus, during prolonged dosing of an aerosol, exhaled CO2 might accumulate within a tight-fitting mask and form a large component of rebreathed air. Most commercially available inhalation facemasks for infants are intended for metered dose or dry powder inhalers, which require only very short dosing (2-3 breaths). Such short dosing
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