Investigators: Alexander Larcombe, Britta Regli-von Ungern, Natalie Anderson
External collaborators: Associate Professor Benjamin Mullins (Curtin University of Technology)
Plain language summary: This project will use computational methods to assess the deposition of e-cigarette aerosols in the lungs, and the distribution of chemicals within e-cigarette aerosols throughout the body. In this way, we will be able to assess the potential health effects of electronic cigarettes without resorting to complex exposure studies.
Project description:
Electronic nicotine delivery systems (ENDS) have a relatively short and controversial existence to date. Use of ENDS has expanded rapidly worldwide, primarily as perceived smoking cessation aids. Fuelled by consumer demand and market competition, new ENDS devices and working fluids (e-fluid) are constantly being introduced, thus, there is a plenitude of conflicting and possibly outdated evidence in research. Furthermore, evidence is limited to that obtained by animal, and in vitro models, as long-term human exposure studies are ethically and logistically challenging. Animal and in vitro models require lung site-specific dosimetry data in order to extrapolate, or validate respectively, their effect on human health. Consequently, chronic health risks of these devices to humans are largely unknown. Indeed, to meet the challenge of the consumer market in ENDS research it is essential to improve our understanding of the underlying mechanisms behind ENDS aerosol exposure in humans.
A mechanistic understanding will provide a framework for bridging the gap between animal, in vitro models, and humans. This thesis will use a ‘bottom up’ (mechanistic) approach, by applying a validated and biologically realistic computational fluid-particle dynamics (CFPD) model to simulate human lung deposition of the ENDS aerosol. In addition, simulated ENDS exposure conditions will mimic that of the real-world user environment, by investigating various combinations of e-fluid excipient ratios, and deposition in a chronic lung condition specific to that of an ex-smoker. The lung deposition data obtained by these CFPD simulations will then be coupled with physiologically based pharmacokinetics to explain the clearance of the aerosol in the human system. Models created with CFPD here can be applied to any current or new device, thus tackling the evolving and expanding market, and bridging known research gaps.