Hardware and software developments to determine the health effects of inhaled aerosols.

The geometry of airways will be generated by medical image techniques. Numerical models and aerosol measuring systems will be developed to analyse inhaled aerosol deposition. Human and in-vitro experiments will then validate the results.

Inhaled air pollutants can cause several serious lung diseases. At the same time, delivery of aerosol drugs into the lung for the treatment of asthma and other lung disorders is more and more widespread. Furthermore, the delivery of therapeutic aerosols into the systemic circulation via the lung is a promising avenue. In order to study the adverse health effects of detrimental aerosols and to deliver the right dose of medication to the right locations of the respiratory system, detailed knowledge of aerosol transport and deposition within the airways is necessary. The deposition of inhaled particles is highly non-uniform within the airways. Several respiratory diseases originate from the large local, cellular burdens, which may develop even at low average doses. It is not possible to describe the local distribution of burden with the traditional methods or analytical lung models. The characterisation of this local non-uniformity, both in the case of air pollutants and aerosol medicines, is a key issue in the technologies of inhalation toxicology and aerosol therapy. Through continuously enhancing computer capacities, numerical modelling might become a powerful and promising method. Development and application of such techniques would allow us to simulate the fate of inhaled aerosols as well as their health effects after the deposition. By the application of computational fluid and particle dynamics methods, it becomes possible to characterise the local features of aerosol deposition and action. This is important because it is well known that the airway deposition is strongly non-uniform and, according to the latest findings, the initiation of lung disorders is also highly site specific. However, these numerical computations require the numerical reconstruction of three-dimensional lung geometries. In the frame of this project, construction of the realistic airway geometry is also planned. Airflow, inhaled particle deposition and micro-dosimetric computations in the reconstructed airways will also be performed. Two new instruments will be developed and validated to improve aerosol therapy and aerosol measuring techniques. Markets for the products will also be searched. One product of the planned efforts will be the numerical reconstruction of the three-dimensional geometry of the upper and large bronchial airways. Most of the airway deposition models suppose uniform deposition distribution along the airways. As a consequence of the fast development of the computational fluid dynamics (CFD) methods, there is a great need for the numerical reconstruction of the three-dimensional geometry of the airways, which has several possible application directions e.g. aerosol drug delivery optimisation, risk analysis in inhalation toxicology, limitation of spreading infectious diseases, prevention or therapy for airway allergy. Another product of the planned project is an aerosol measuring system which is especially developed for the measurement of inhaled and exhaled aerosols in the whole particle size range of the respirable particulate matter that is from 1 nanometre to 100 micrometres. The two instruments will be widely validated and tested by in-vivo and in-vitro experiments and numerical computational fluid dynamic simulations. In light of the above objectives, the tasks of the project are grouped into three workpackages: WORKPACKAGE I: Numerical generation of extrathoracic and central human airway geometries by different medical images and other techniques. This implies the reconstruction of the three-dimensional surfaces of the airways from planar image series of high resolution computer tomography, micro-tomography, magnetic resonance images, and digital photo techniques applied on sliced lung casts. The upper airways, the trachea and the main bronchi are wide enough for the application of high resolution computer tomography. The geometry of the smaller bronchial airways will be numerically generated by the preparation of lung casts. The lung casts must reserve the original shape of the airways, which requires special new preparation methods. Current lung cast technologies should be improved because the fine structure of the carina ridges of the bronchial bifurcations show shapes that are too narrow and also the cross sections download to the carina at the beginning of the daughter airways being narrowed. In the planned new instrument, the excised lung will be inserted in a mixture of water and fine air bubbles where the density of the medium will be about 0.2 kg/litre. The air pressure over this medium will be a little bit less than in the surroundings. Through an appropriate inhaler, the excited lung will inhale in a realistic way. Under these circumstances, the shape of the lung will be similar to that of the living lung. The filling material will be a mixture of poly-vinyl-chloride and glass powder to receive appropriate consistency. This plastic cannot contain air bubbles, thus it will be placed into a vacuum right before the moulding. The shape of the cast will be numerically generated by computer tomography images in case of the central airways and by micro tomography images in case of smaller bronchi. The appropriate numerical surface and mesh generation demands the application of a series of 3D software. Airflow and particle deposition patterns of respirable aerosol particles will be numerically simulated in the realistic geometry of the upper and bronchial airways by the FLUENT computational fluid dynamics (CFD) commercial code. Steady state and time dependent calculations will be performed in the entire 1 nanometre - 100 micrometre particle size range. The effect of turbulence will also be analysed. Hollow lung casts will also be developed during the experiments, while the flow and particle analyser system developed in Workpackage II will be tested and validated by hollow cast flow and particle measurements. This instrument will also be applied for the validation of the CFD calculations. Radio-labelled aerosols will also be applied to measure the deposition distributions in the hollow casts and in vivo in voluntaries. WORKPACKAGE II: A new instrument will be developed and will be able to characterise the physical properties of medical aerosols. This scanning differential mobility analyser will be able to measure the particle size distributions from 5 nanometre (nm) to 100 micrometer particle sizes in parallel with the electric charge distributions of the particles. With this device, the inhaled and exhaled size and electric charge distributions of medical aerosols, and the fractionated deposition in the human respiratory system can be measured together with the electric effects. It makes it possible to determine the deposited fractions in the respiratory system in different size fractions and electric charges. The instruments (software and hardware) will be tested and applied to validate each other. WORKPACKAGE III: Regional measurements of particle deposition in the size range between 10 nm and 10 micrometres will be performed on the airway cast for different breathing conditions. Spontaneous breathing profiles will be recorded on subjects and then simulated during aerosol inhalation in the cast. Apart from the total deposition, deposition fractions will also be studied in single bifurcations using radio-labelled particles. Deposition will also be studied using fixed breathing patterns. Experimental deposition data will be compared to numerical simulations and to deposition data obtained on human subjects. Keywords: Inhaled aerosols, health effects, aerosol instruments.
Project ID: 
3 977
Start date: 
Project Duration: 
Project costs: 
1 200 000.00€
Technological Area: 
Environmental Medicine, Social Medicine,Sports Medicine technology
Market Area: 
Diagnostic services

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