Regional aerosol deposition in the human airways: the SimInhale benchmark case and a critical assessment of in silico methods

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 15 years 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

Analysis of Fiber deposition using Automatic Image Processing Method

Fibers are permanent threat for a human health. They have an ability to penetrate deeper in the human lung, deposit there and cause health hazards, e.glung cancer. An experiment was carried out to gain more data about deposition of fibers. Monodisperse glass fibers were delivered into a realistic model of human airways with an inspiratory flow rate of 30 l/min. Replica included human airways from oral cavity up to seventh generation of branching. Deposited fibers were rinsed from the model and placed on nitrocellulose filters after the delivery. A new novel method was established for deposition data acquisition. The method is based on a principle of image analysis. The images were captured by high definition camera attached to a phase contrast microscope. Results of new method were compared with standard PCM method, which follows methodology NIOSH 7400, and a good match was found. The new method was found applicable for evaluation of fibers and deposition fraction and deposition efficiency were calculated afterwards

Velocity profiles in idealized model of human respiratory tract

This article deals with numerical simulation focused on velocity profiles in idealized model of human upper airways during steady inspiration. Three r gimes of breathing were investigated: Resting condition, Deep breathing and Light activity which correspond to most common regimes used for experiments and simulations. Calculation was validated with experimental data given by Phase Doppler Anemometry performed on the model with same geometry. This comparison was made in multiple points which form one cross-section in trachea near first bifurcation of bronchial tree. Development of velocity profile in trachea during steady inspiration was discussed with respect for common phenomenon formed in trachea and for future research of transport of aerosol particles in human respiratory tract

Application of Positron Emission Tomography to Aerosol Transport Research in a Model of Human Lungs

Positron Emission Tomography (PET) is a convenient method for measurement of aerosol deposition in complex models of lungs. It allows not only the evaluation of regional deposition characteristics but also precisely detects deposition hot spots. The method is based on a detection of a pair of annihilation photons moving in opposite directions as a result of positron – electron interaction after the positron emission decay of a suitable radioisotope. Liquid di(2-ethylhexyl) sebacate (DEHS) particles tagged with fluorine-18 as a radioactive tracer were generated by condensation monodisperse aerosol generator. Aerosol deposition was measured for three different inhalation flowrates and for two sizes of particles. Combination of PET with Computed Tomography (CT) in one device allowed precise localisation of particular segments of the model. The results proved correlation of deposition efficiency with Stokes number, which means that the main deposition mechanism is inertial impaction. As a next task the methodology for tagging the solid aerosol particles with radioactive tracer will be developed and deposition of porous and fiber aerosols will be measured

Does a Soft Macroeconomic Environment Induce Restructuring on the Microeconomic Level During the Transition Period? Evidence from Investment Behavior of Czech Enterprises

The paper analyzes investment behavior of industrial enterprises in the period immediately following price and foreign trade liberalization in the Czech Republic. It also focuses on the effect of "soft" macroeconomic environment on the microeconomic decisions. A dynamic investment function with symmetric adjustment cost function based on the Euler equation has been estimated. The derived and estimated investment function accounts for export sales in order to determine whether firms evaluate production for domestic and foreign markets differently, i.e, use the advantage of an undervalued currency. The estimation was conducted on two-year firm-level panel data from 1992 and 1993. The first major result of the empirical analysis suggests that there is no evidence that firms treat domestic sales and exports differently in the context of the adjustment cost function. The second remarkable finding contradicts the common view that firms in the transitional environment have short-term horizons. Both these findings could be interpreted as strong evidence against the idea of economic policy helping firms within a temporary soft macroeconomic environment. No evidence was found against the applicability of the constant returns to scale assumption on the Cobb-Douglas production function within the analyzed framework.http://deepblue.lib.umich.edu/bitstream/2027.42/39621/3/wp235.pd

Multicomponent aerosol particle deposition in a realistic cast of the human upper respiratory tract

Inhalation of aerosols generated by electronic cigarettes leads to deposition of multiple chemical compounds in the human airways. In this work, an experimental method to determine regional deposition of multicomponent aerosols in an in vitro segmented, realistic human lung geometry was developed and applied to two aerosols, i.e. a monodisperse glycerol aerosol and a multicomponent aerosol. The method comprised the following steps: (1) lung cast model preparation, (2) aerosol generation and exposure, (3) extraction of deposited mass, (4) chemical quantification and (5) data processing. The method showed good agreement with literature data for the deposition efficiency when using a monodisperse glycerol aerosol, with a mass median aerodynamic diameter (MMAD) of 2.3 μm and a constant flow rate of 15 L/min. The highest deposition surface density rate was observed in the bifurcation segments, indicating inertial impaction deposition. The experimental method was also applied to the deposition of a nebulized multicomponent aerosol with a MMAD of 0.50 μm and a constant flow rate of 15 L/min. The deposited amounts of glycerol, propylene glycol and nicotine were quantified. The three analyzed compounds showed similar deposition patterns and fractions as for the monodisperse glycerol aerosol, indicating that the compounds most likely deposited as parts of the same droplets. The developed method can be used to determine regional deposition for multicomponent aerosols, provided that the compounds are of low volatility. The generated data can be used to validate aerosol deposition simulations and to gain insight in deposition of electronic cigarette aerosols in human airways