The execution of the project was carried out according to the project schedule. The proposed tasks and subtasks were all completed. During the project good cooperation has formed between the research institutions and the companies involved in research and development activities. This is well conformed by the successful application of the scientific and technical results. The participants of the project held numerous meetings during the execution of the project, which promoted the progress of the research tasks. Most of the results were presented on international conferences and journals. The references of the numerous publications (3 book chapters, 15 articles in international journals with impact factor, 1 paper in Hungarian journal, 9 publications in conference books and 32 conference abstracts) are listed in the end of this report. The utilization of some of the results has already been completed; other results are near to utilisation in the industry. While fundamental and applied research was in the focus of the first two reporting periods of the project, in the third and fourth periods great emphasis has been laid on the exploitation and marketing of the products. This task was leaded by the two companies participating in the project.

Several result were achieved throughout the project that are unique both on national and international level. During project execution a measuring device, which is based on state-of-the-art technologies, has been developed for the investigation of the air flow filed, particle transport and deposition in hollow replicas of the human airway system. The device composed of the glass pipe structure, the realistic hollow resin lung cast and the optical measuring system that measures the flow and deposition features within these replicas means considerable scientific result.          The stochastic lung deposition model, which operates in the whole respiratory tract, and the computational fluid dynamics (CFD) model, which describes the regional deposition processes, are mathematical models based on the latest scientific results and are unique within their own category. Utilising these models user friendly software has been elaborated, which can be valuable product on the market. Some units of the applied measuring device, which were developed in the frame of this project, are important product of the national and international market on their own. The most important results reached in the reporting periods are listed below by subtasks:

 

 

 

First reporting period (1 January 2007 – 31 August 2007)

 

Subtask 1.1.: The professional issues of the project were analysed and planned at the beginning of the project during two consecutive project meetings and several phone calls. At the same meetings the main aspects of the project coordination and partnership were debated. Since Hungarian partners were the first to apply and get funded the plans were elaborated for two scenarios: acceptance or rejection of the national proposals of the Austrian or German partners.

Subtask 1.2.: CT image series were acquired from the nasal, oral, pharyngeal and laryngeal airways. Morphologically realistic three dimensional airways were digitally reconstructed based on these planar slices.

Subtask 1.3.: Several bronchial airway replicas were prepared in order to optimise the process and to identify the most appropriate technique of cast preparation. During this multistage process a large number of setup options and materials were checked and tested.

Subtask 1.4: Numerical discretization of the idealized airway geometries and realistic ones has been realised by the application of appropriate computational meshes. In this way the digital geometries were converted into computational domains for future fluid and particle dynamics simulations.

Subtask 1.5.: CFPD (computational fluid and particle dynamics) computations have been performed in a geometry consisting of trachea and central bronchi up to the fifth airway generation. Results highlighted the inhomogeneous spatial distribution of particle deposition within the central airways. The strongly nonuniform character of particle deposition patterns was stated also by parallel XRF measurements and computations in realistic rat airways.

Subtask 1.8.: Charge and concentration measurement methods applicable in case of human inhalation experiments were selected, set up and developed for particles in the 5 nm – 100 μm size range. Furthermore, processing procedures of experimentally measured data were elaborated.

 

Second reporting period (1 September 2007 – 31 August 2008)

Subtask 2.2. Further CT image acquisition from the upper airways of another subject (with gender opposite to the one examined in the first reporting period) has been completed. A 3D digital model geometry was also created. The new 3D model geometry has been compared to the ones composed before in order to highlight the intersubject differences.

Subtask 2.3.: By solving the problems encountered in the previous reporting period regarding the preparation of airway casts (bubbles, wholes etc.) new replicas of near the whole bronchial tree have been prepared.

Subtask 2.4.: Numerical meshes were applied to the geometries reconstructed in the frame of subtask 2.3. A special size function technique has been applied to adequately mesh the highly complex geometries. The resulting mesh was unstructured and inhomogeneous.

Subtask 2.5: The working group of the Hungarian Academy of Sciences KFKI Atomic Energy Research Institute has been performed air and particle transport simulations in idealised and realistic geometries. The geometry reconstructed based on CT images has been scaled so that its tracheal inlet had the same diameter like the idealised one. In this way it became possible to compare the results obtained on idealized geometries on those provided by realistic airways.

Subtask 2.6.: Two complex central airway models were constructed from straight glass tubes. The models were connected to the aerosol generator and breathing simulator devices developed in the frame of subtask 2.8. Air velocity values have been determined in some special locations inside the glass models.

Subtask 2.7.: Results of the aerosol inhalation experiments performed by EUREKA partners (Inamed GmbH, GSF) have been processed and compared to the computational results of the Déri project (Hungarian Project).

Subtask 2.8.: Aerosol generator and measurement devices have been further developed. Aerosols were generated in the 5 nm – 100 mm size range. Airflow velocity profiles have been measured in regions of interest of the airway models.

 

Third reporting period (1 September2008 – 31 August 2009)

Subtask 3.5.: In the frame of this task, computational fluid dynamics based calculations were carried out on the transport and deposition of inhaled particles in the regions of the respiratory system most preferred by the malignant mutations that is the large bronchi of the central airway system for inhalation conditions and particle parameters that were considered to be the most important. Further, numerical algorithms were developed and applied for the quantification of local distribution of particle deposition patterns.

Subtask 3.6.: A novel technique has been elaborated for the fabrication of realistic hollow airway replicas. Laser based measurement were completed for particle transport velocities in the constructed hollow casts applying a Doppler method. Based on the results of the measurements velocity profiles were reconstructed in different locations of the pipe system.

Subtask 3.7.: The results of the in vivo experiments carried out by the Germen partners of the international EUREKA project were compared with the results of the simulations completed by the Hungarian participants of the Déri Miksa project. In the case of both measuring techniques, the comparisons were made for healthy, COPD (chonic obstructive pulmonary disease) as well as asthmatic airways. In all the cases, the results showed good agreement.

Subtask 3.8.: The Testovent probe applied in the previous reporting period for the determination of the aerosol parameters was replaced by a Laser Doppler instrument since this needs not to be placed in the flow space and, thus, the flow is not perturbed. Particle velocities, size distributions and particle concentrations were determined by the help of this device. The results were compared to those obtained by the numerical models elaborated for this purpose. The results were again in good accordance with each other.

Subtask 3.9.: The measuring device developed in the previous reporting period was completed with five new units. The instrument was utilised to measure the flow patterns characteristic in our glass and resin replicas. By doing so, the testing of the device was also performed.

Subtask 3.10.: In the frame of this task the validation of the lung models developed and utilised during this project were carried out. Furthermore, CFD calculations were completed in the integrated geometry containing the nose, pharynx, larynx, trachea and central airway system. The results of the numerical model were compared with the results of both in vitro and in vivo measurements. These comparisons were performed by the calculations of flow profiles and deposition patterns. The values obtained by different methods usually were in good agreement with each other. The deviations were within reasonable limits.

Subtask 3.11.: The specifications and information of the potential consumers were started. The Aerosol Department of the University of Vienna, the GRIMM Aerosoltechnik GmbH+Co.KG Ainring, the Joint Research Centre, the Institute for Environment ( Ispra, Italy), the American TSI Co and the University of Veszprém collaborated in performing this task. The products were also introduced in the ÖKOTECH exhibitions. The designs of the fliers were also finished.

 

 

 

Forth reporting period (1 September2009 – 31 December 2009)

Subtask 4.8.:  The device jointly constructed was further developed and some new measurements were completed. The Doppler velocity measuring device was developed in two ways in this period: a) the Nd:YAG laser was replaced by a He-Ne laser and b) we succeeded in making some areas of the resin replica transparent enough.

Subtask4.9.:  The results of the aerosol measurements were collected, summarized and analysed. The completed measurements yielded a series of new results since, to the best of our knowledge, up to the present similar measurements were never performed on complex airway replicas made of glass or resin. A part of these results have been published and presented in international conferences. The attained results are in line with the results of the models.

 

Subtask 4.10.: The lung models were jointly tested and checked again. Lung diseases were simulated with the help of the whole respiratory system deposition models and additional calculations were performed with the help of the CFD based models. The elaborated whole respiratory tract aerosol deposition model and software is ready for the market.

Subtask 4.11.:  Measures were taken to find new partners to expand the possibilities of marketing. We have contacted several companies and new project proposals were submitted to some of these companies. The dissemination of the products was continued. Several possibilities were developed for the potential further improvements of the products.

Subtask 4.12.:  The final reports and overall documentations were prepared.

Subtask 4.13.:  The closure of the project is started. The final documentation is prepared.