Aerosols are well recognized as an effective means of delivery of therapeutic agents. However, our knowledge of aerosol behavior in human subjects becomes increasingly poor as subject age is reduced. The paucity of pediatric data are due in part to issues associated with the use of in vivo imaging in infants and children. Being at the very youngest end of the age spectrum, neonates are at the frontiers of our predictive understanding of aerosol deposition. The youngest age for which extensive deposition data for micrometer sized aerosol particles has previously been obtained is that of Swift (1), who measured nasal deposition in a replica of a 6-wk-old female infant as a function of particle size and flow rate. Minocchieri et al. (2), in their article in the present issue, have surpassed this previously youngest age by 9 wk, building a replica from an MRI scan of a 3 wk preterm neonate and measuring deposition of a nebulized budesonide aerosol in this replica. Comparing Minocchieri et al.'s data to that of Swift's, at flow rates of 1 and 5 L/min, Minocchieri et al. find aerosol delivery to the lung is about half that seen in Swift's 6-wk-old subject, while at 10 L/min their data are similar to Swift's. Minocchieri et al. note that they find less delivery to the lung than in previously published data in the SAINT replica of a 9 mo old (3). Assuming that infants have similarly large intersubject variations in their extrathoracic airways as seen in adults, a relevant question is how much of these differences is due to intersubject variation at a given age and how much is due to age alone? In other words, does Minocchieri et al.'s subject have particularly high nasal deposition for subjects of that age while Swift's subject has particularly low nasal deposition? Or would all subjects that are 9 wk apart at these ages show such dramatic differences in nasal deposition?

In adults, intersubject variability in extrathoracic deposition is a primary cause of intersubject variability in lung dose (4). Recent work in adults and older children has shown that intersubject variability can be collapsed by incorporation of subject-dependent length scales into the relevant dimensionless mechanical parameters that govern aerosol behavior (5–8). Would such a treatment allow prediction of the above differences in infant deposition? This is an intriguing question that arises when reading Minocchieri et al.'s work, and the answer is far from being esoteric, since it hints at the hope of a priori prediction of neonatal lung delivery. Such predictive power already exists for adult subjects, and is simple enough that it has been incorporated into an on-line calculator (9) that allows the user to quickly predict aerosol deposition, thereby allowing improved drug delivery in adults and older children. Can we extend to neonates the powerful predictive understanding that we currently have in older subjects? Minocchieri et al. show that it is possible to obtain in vitro aerosol deposition data in replicas of neonatal extrathoracic airways, so the answer to this question will surely not be long in coming.

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