Regional deposition effects are important in the pulmonary delivery of drugs intended for the topical treatment of respiratory ailments. They also play a critical role in the systemic delivery of drugs with limited lung bioavailability. In recent years, significant improvements in the quality of pulmonary imaging have taken place, however the resolution of current imaging modalities remains inadequate for quantifying regional deposition. Computational Fluid-Particle Dynamics (CFPD) can fill this gap by providing detailed information about regional deposition in the extrathoracic and conducting airways. It is therefore not surprising that the last 15years have seen an exponential growth in the application of CFPD methods in this area. Survey of the recent literature however, reveals a wide variability in the range of modelling approaches used and in the assumptions made about important physical processes taking place during aerosol inhalation. The purpose of this work is to provide a concise critical review of the computational approaches used to date, and to present a benchmark case for validation of future studies in the upper airways. In the spirit of providing the wider community with a reference for quality assurance of CFPD studies, in vitro deposition measurements have been conducted in a human-based model of the upper airways, and several groups within MP1404 SimInhale have computed the same case using a variety of simulation and discretization approaches. Here, we report the results of this collaborative effort and provide a critical discussion of the performance of the various simulation methods. The benchmark case, in vitro deposition data and in silico results will be published online and made available to the wider community. Particle image velocimetry measurements of the flow, as well as additional numerical results from the community, will be appended to the online database as they become available in the future.
The transmissibility and pandemic potential of influenza viruses depends on their ability to efficiently replicate and be released from an infected host, retain viability as they pass through the environment, and then initiate infection in the next host. There is a significant gap in knowledge about viral properties that enable survival of influenza viruses between hosts, due to a lack of experimental methods to reliably isolate viable virus from the air. Using a novel technique, we isolate and characterise infectious virus from droplets emitted by 2009 pandemic H1N1-infected ferrets. We demonstrate that infectious virus is predominantly released early after infection. A virus containing a mutation destabilising the haemagglutinin (HA) surface protein displayed reduced survival in air. Infectious virus recovered from droplets exhaled by ferrets inoculated with this virus contained mutations that conferred restabilisation of HA, indicating the importance of influenza HA stability for betweenhost survival. Using this unique approach can improve knowledge about the determinants and mechanisms of influenza transmissibility and ultimately could be applied to studies of airborne virus exhaled from infected people.
A robust immersed boundary method for semi-implicit discretizations of the Navier-Stokes equations on curvilinear grids is presented. No-slip conditions are enforced via momentum forcing, and mass conservation at the immersed boundary is satisfied via a mass source term developed for moving bodies. The errors associated with an explicit evaluation of the momentum forcing are analysed, and their influence on the stability of the underlying Navier-Stokes solver is examined. An iterative approach to compute the forcing term implicitly is proposed, which reduces the errors at the boundary and retains the stability guarantees of the original semi-implicit discretization of the Navier-Stokes equations. The implementation in generalized curvilinear coordinates and the treatment of moving boundaries are presented, followed by a number of test cases. The tests include stationary and moving boundaries and curvilinear grid problems (decaying vortex problem, stationary cylinder, flow in 90• bend in circular duct and oscillating cylinder in fluid at rest).
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