Realistic Model Of Human Airways Research Articles

In silico investigation of inhalation condition impacts on hygroscopic growth and deposition of salbutamol sulphate in human airways

The objective of this study is to explore the transport, size growth, and deposition of Salbutamol Sulphate (SS) using Computational Fluid Dynamics (CFD). A CT-based realistic model of human airways from the oral cavity to the 5th generation of the lung was utilized as the computational domain. Four Test Cases (TC) with varying temperature and relative humidity (RH) under two inspiratory waveforms were considered to completely evaluate the impact of inhalation conditions on particle growth. Salbutamol Sulphate (SS) is a β2-adrenergic agonist and has been extensively used for asthma treatment. A monodispersed distribution of SS particles with an initial diameter of 167 nm was considered at the mouth inlet based on pharmaceutical data. Results indicated that inhalation of saturated/supersaturated air (RH>100%) leads to significant hygroscopic growth of SS particles with a factor of 10. In addition, the deposition efficiency of SS particles under the Quick and Deep (QD) inhalation profile was enhanced as the flow temperature and humidity increased. However, the implementation of Slow and Deep (SD) inspiratory waveform revealed that the same particle size growth is achieved in the respiratory system with lower deposition efficiency in the mouth-throat (less than 3%) and tracheobronchial airway (less than 2.18%). For the escaped particles form the right lung, in the SD waveform under TC 3, the maximum particle size distribution was for 600 nm particles with 25% probability. In the left lung, 30% of the particles were increased up to 950 nm in size. For the QD waveform in TC 3 and TC4, the most frequent particles were 800 nm with 36% probability. This holds practical significance in the context of deep lung delivery for asthmatic patients with enhanced deposition efficiency and large particle size. The findings of the present study can contribute to the development of targeted drug delivery strategies for the treatment of pulmonary diseases using hygroscopic dry powder formulations.

Time-resolved characteristics of oscillatory particle-laden air flow in a realistic human airway model

Human airways represent a complex flow system with a spatially and temporally variable character of air flow during respiration. In this paper, we experimentally studied the oscillatory flow of air with monodispersed micron-sized liquid particles in a transparent, anatomically realistic model of human upper airways and several bronchi generations using phase-Doppler anemometry (PDA). The PDA provided point-wise high-frequency measurements of axial velocities of individual aerosol particles in multiple positions of the airways (in the trachea and the upper bronchi) for three breathing regimes with a sinusoidal course. Typical time-resolved velocity plots at several positions within the model were documented and analysed using dimensionless criteria. Local mean air velocity and turbulence time-lines disclosed specific flow dynamic features in the multiple bifurcation system, namely the transit of vortical structures, oscillations induced by flow reversals, and inspiratory flow separations behind bifurcations. The results elucidated the laminar, transitional and turbulent flows during inspiratory and expiratory breathing phases. The character of the flow varies significantly with position in the airways, while the breathing regime has a generally low effect on the flow character. Inspection of the flow in the terminal branches indicated the need to add further branches for more realistic results there.

Computational investigation of flow characteristics and particle deposition patterns in a realistic human airway model under different breathing conditions

Airborne particle pollution causes a range of respiratory and cardiovascular disorders by entering the human respiratory system through the breathing process. The administration of pharmaceutical particles by inhalation is another effective way to treat pulmonary illnesses. Studying particle deposition in the respiratory system during human breathing is crucial to maintaining human health. This necessity served as the impetus for this work, which aims to investigate how the airflow and particles' deposition are influenced by constant inhalation and circulatory breathing, particle diameter, and changes in airflow rate. The focus of this paper is to compare the particle deposition results of circulatory respiration with constant respiration. Based on computed tomography (CT) scan pictures, a precise human airway model from the mouth cavity to the fifth-generation bronchi was created. Flow fields and particle deposition inside the respiratory tract were examined at varied breathing rates (30, 60, and 90 L/min of constant and circulatory breathing) and varying haled particle sizes (5 and 10 µm). The results showed that the oropharyngeal area is often where the majority of particles are deposited. The particle distribution fraction is more significant in the bronchial area than the oropharyngeal region due to lower inhalation velocities and smaller particle sizes. For particles with a diameter of 5 µm, constant respiration and circulatory respiration have virtually identical particle distribution fractions in each region. For particles with a diameter of 10 µm, the particle distribution fraction for circulatory respiration is slightly higher than for constant respiration in the bronchial region as the flow rate increases. For both constant and circulatory respiration, particles are deposited more in the right lung and less in the left. These results contribute to further research on respiratory diseases caused by inhaled particles and guide inhalation therapy for better treatment outcomes.

Effect of transient breathing cycle on the deposition of micro and nanoparticles on respiratory walls

Background and objectiveFrom various perspectives (e.g. inhalation exposure and drug delivery), it is important to provide insights into the behavior of inhaled particles in the human respiratory system. Although most of the experimental and numerical studies have relied on an assumption of steady inhalation, the transient breathing profile is a key factor in particle deposition in the respiratory tract. In this study, particle transportation and deposition were predicted in a realistic human airway model during a breathing cycle and the effects of steady-state and transient flows on the deposition fraction were observed using computational fluid dynamics. MethodsTwo transient breathing cycles with different respiratory durations were considered to evaluate the effects of respiration duration on particle transport and deposition characteristics. Two types of steady breathing conditions with corresponding steady-state respiratory volumes were reproduced. The Lagrangian discrete phase model approach was used to investigate particle transportation and deposition under transient breathing conditions. Additionally, the Eulerian approach was used to analyze the transport of nanoparticles in the gas phase. A total of >50,000 monodispersed particles with aerodynamic diameters ranging between 2 nm and 10 μm were selected for comprehensive deposition predictions for particle sizes ranging from the nano- to microscale. ResultsThe predicted results were compared with the experimental data. The particle deposition fraction in the nasal cavity and tracheal regions showed differences between the steady and transient simulations. In addition, particle analysis under steady inhalation conditions cannot accurately predict particle transportation and deposition in the lower airway. Furthermore, the breathing cycle had a significant effect on the deposition fraction of the particles and the behavior of the inhaled particles. ConclusionsTransient simulation mimicking the breathing cycle was observed to be an important factor in accurately predicting the transportation and deposition of particles in the respiratory tract.

Evaluation of Airflow Sensitivity to the Truncation Level of a Realistic Human Airway Model in an Accurate Numerical Simulation.

Background: The truncation level of human airways is an influential factor in the analysis of respiratory flow in numerical simulations. Due to computational limitations and limited resolution of diagnostic medical imaging equipment, a truncated geometry of airways is always investigated.Objective: This study aimed to employ image-based geometries with zero generation and 5th-generation truncation levels and assess bronchial airways truncation’s effect on tracheal airflow characteristics.Material and Methods: In this numerical study, computational fluid dynamics was employed to solve the respiratory flow in a realistic human airway model using the large eddy simulation technique coupling with the wall-adapting local eddy-viscosity (WALE) sub-grid scale model. The accuracy of numerical simulations was ensured by examining the large eddy simulation index of quality and Kolmogorov’s K-5/3 law.Results: The turbulent kinetic energy along the trachea has increased abnormally in the geometry with the zero-generation truncation level, and more severe fluctuations occurred in the velocity field of this geometry, which increased the tendency of each point to rotate. Compared to the extended model, the airflow’s more chaotic behavior prevented larger-scale vortices from forming in the geometry with the zero-generation truncation level. Larger-scale vortices in the extended model caused the primary flow passing next to the vortices to accelerate more intensely, increasing the wall shear stress peaks in this geometry.Conclusion: Eliminating the bronchial airways caused changes in tracheal airflow characteristics.

Proposal of selective wedge instillation of pulmonary surfactant for COVID-19 pneumonia based on computational fluid dynamics simulation

BackgroundThe most important target cell of SARS-CoV-2 is Type II pneumocyte which produces and secretes pulmonary surfactant (PS) that prevents alveolar collapse. PS instillation therapy is dramatically effective for infant respiratory distress syndrome but has been clinically ineffective for ARDS. Nowadays, ARDS is regarded as non-cardiogenic pulmonary edema with vascular hyper-permeability regardless of direct relation to PS dysfunction. However, there is a possibility that this ineffectiveness of PS instillation for ARDS is caused by insufficient delivery. Then, we performed PS instillation simulation with realistic human airway models by the use of computational fluid dynamics, and investigated how instilled PS would move in the liquid layer covering the airway wall and reach to alveolar regions.MethodsTwo types of 3D human airway models were prepared: one was from the trachea to the lobular bronchi and the other was from a subsegmental bronchus to respiratory bronchioles. The thickness of the liquid layer covering the airway was assigned as 14 % of the inner radius of the airway segment. The liquid layer was assumed to be replaced by an instilled PS. The flow rate of the instilled PS was assigned a constant value, which was determined by the total amount and instillation time in clinical use. The PS concentration of the liquid layer during instillation was computed by solving the advective-diffusion equation.ResultsThe driving pressure from the trachea to respiratory bronchioles was calculated at 317 cmH2O, which is about 20 times of a standard value in conventional PS instillation method where the driving pressure was given by difference between inspiratory and end-expiratory pressures of a ventilator. It means that almost all PS does not reach the alveolar regions but moves to and fro within the airway according to the change in ventilator pressure. The driving pressure from subsegmental bronchus was calculated at 273 cm H2O, that is clinically possible by wedge instillation under bronchoscopic observation.ConclusionsThe simulation study has revealed that selective wedge instillation under bronchoscopic observation should be tried for COVID-19 pneumonia before the onset of ARDS. It will be also useful for preventing secondary lung fibrosis.

Inhalation airflow and ventilation efficiency in subject-specific human upper airways

The present numerical study investigated the transportation time of the inhaled chemicals in three realistic human airway models by adopting a methodology from the field of the building ventilation. Two indexes including “scale of ventilation efficiency 3 (SVE3)” and “local purging flow rate (L-PFR)” were used to evaluate the respective arrival time and staying time under different inhalation flow rates. The general trend of the SVE3 was predicted as expected and the exceptions within the nasal cavities were attributed to the uneven allocation of the inhaled flow between the internal channels and the formation of the vortex circulation therein. The complicated situation of the L-PFR was also explained by the structure constrains. Moreover, the variation of the two indexes with the flow rate was sensitive to the inter-subjective differences but the distribution pattern was not changed significantly. By combining the SVE3 and L-PFR, it could help with assessing the potential effect of the inhaled chemicals on the human health for engineering applications to which the relative impacts are more interested than the absolute value. But for the precise evaluation regarding a specific chemical, comprehensive simulation is still necessary with the surface adsorption included under realistic respiration cycles.

Investigation of flow pattern in upper human airway including oral and nasal inhalation by PIV and CFD

Breathing is one of the most essential processes in the human body. The basic functions of breathing are to exchange gases (supplying oxygen from ambient air and removing carbon dioxide from the blood) and also to exchange heat and moisture through mucous surfaces of the airway. During an average lifetime, human beings experience significant exposure to indoor air and countless of contaminants/particles via inhalation. In this study, experimental and numerical results of flow fields in a realistic respiratory model were obtained. Flow patterns in a realistic replica model of the human respiratory tract were investigated with particle image velocimetry (PIV) under three constant breathing conditions; 7.5, 15 and 30 L/min. Computational fluid dynamics (CFD) analyses were conducted on turbulent models with boundary conditions corresponding to the experimental models. We used four RANS turbulence models to predict airflow in a realistic human airway model: two low Reynolds (Re) number-type k–ε turbulence models, RNG k–ε model, and the SST k–ω model. The CFD results were compared with PIV data and showed relatively good agreement in trachea region in all cases.

CFD simulation of airflow behavior and particle transport and deposition in different breathing conditions through the realistic model of human airways

In this work, the airflow behavior and particle transport and deposition in different breathing conditions such as light breathing condition (15L/min), normal breathing condition (30L/min) and heavy breathing condition (60L/min) are investigated. The realistic geometry data was reconstructed from CT-scan images of the human airways with 0.5mm thickness of slices. The CT-scan images (DICOM files) are imported in the 3D-DOCTOR software and all slices were segmented. Then, the output has been imported in CATIA-V5 software. Finally, face, volume, mesh and extension tubes at inlet and outlets were created and then imported into ANSYS FLUENT 15. The Lagrangian approach is used to evaluating the transport and deposition of inhaled micro-particles. The presented results showed that for dp=5μm and 10μm, when flow rate =30Lmin and for dp=1μm, when flow rate =15Lmin, the particle deposition fraction have maximum amount. For flow rate =15Lmin and =30Lmin, the maximum deposition occurs in the zone number 1 and for flow rate =60Lmin occurs in the zone number 4. Also, the maximum pressure distribution happens when flow rate =60Lmin which would be acceptable. According to the results, the particles tended to go to the right branch and the minimum number of particles crossed the zone numbers 6 and 11.

Airflow and Aerosol-Drug Delivery in a CT Scan based Human Respiratory Tract with Tumor using CFD

This paper is focused on to study the effect of a tumor present in the respiratory tract (in trachea) on airflow pattern and aerosol-drug deposition. A realistic model of human respiratory tract was constructed from spiral computed tomography (CT) scan data and a bifocal tumor (Glomus tumor) was constructed in the tract. The inspiratory flow characteristics of the realistic human airway models (with and without tumor) was numerically solved using the realizable k turbulence model for airflow and Shear Stress Transport (SST) k-ω turbulence model for two-phase flow. The velocity (contours and vector plots), wall shear stress and deposition efficiency of aerosol were obtained at different locations to the upstream and downstream region of the bifocal tumor in respiratory tract. The flow pattern shows that the maximum flow disturbance occurs around the tumor and at downstream of the flow. Magnitude and location of maximum wall shear stress in the presence of the tumor helps in identifying the extent and probable location of the wall injury during the normal and heavy breathing conditions. Deposition efficiency of aerosol-drug on tumor location will be useful for designing the efficient targeted drug delivery system.

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.g. lung 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.

Power spectral density of velocity fluctuations estimated from phase Doppler data

Laser Doppler Anemometry (LDA) and its modifications such as Phase- Doppler Particle Anemometry (P/DPA) is point-wise method for optical non- intrusive measurement of particle velocity with high data rate. Conversion of the LDA velocity data from temporal to frequency domain - calculation of power spectral density (PSD) of velocity fluctuations, is a non trivial task due to non- equidistant data sampling in time. We briefly discuss possibilities for the PSD estimation and specify limitations caused by seeding density and other factors of the flow and LDA setup. Arbitrary results of LDA measurements are compared with corresponding Hot Wire Anemometry (HWA) data in the frequency domain. Slot correlation (SC) method implemented in software program Kern by Nobach (2006) is used for the PSD estimation. Influence of several input parameters on resulting PSDs is described. Optimum setup of the software for our data of particle-laden air flow in realistic human airway model is documented. Typical character of the flow is described using PSD plots of velocity fluctuations with comments on specific properties of the flow. Some recommendations for improvements of future experiments to acquire better PSD results are given.

Study of cyclic and steady particle motion in a realistic human airway model using phase-Doppler anemometry

Transport and deposition of particles in human airways has been of research interest for many years. Various experimental methods such as constant temperature anemometry, particle image velocimetry and laser-Doppler based techniques were employed for study of aerosol transport in the past.

Development of a realistic human airway model

Numerous models of human lungs with various levels of idealization have been reported in the literature; consequently, results acquired using these models are difficult to compare to in vivo measurements. We have developed a set of model components based on realistic geometries, which permits the analysis of the effects of subsequent model simplification. A realistic digital upper airway geometry except for the lack of an oral cavity has been created which proved suitable both for computational fluid dynamics (CFD) simulations and for the fabrication of physical models. Subsequently, an oral cavity was added to the tracheobronchial geometry. The airway geometry including the oral cavity was adjusted to enable fabrication of a semi-realistic model. Five physical models were created based on these three digital geometries. Two optically transparent models, one with and one without the oral cavity, were constructed for flow velocity measurements, two realistic segmented models, one with and one without the oral cavity, were constructed for particle deposition measurements, and a semi-realistic model with glass cylindrical airways was developed for optical measurements of flow velocity and in situ particle size measurements. One-dimensional phase doppler anemometry measurements were made and compared to the CFD calculations for this model and good agreement was obtained.