Computational Fluid Dynamics as an Emerging Supporting Clinical Tool: Review on Human Airways

Objectives: The main objective of this review article is to evaluate the usability of Computational Fluid Dynamics (CFD) as a supporting clinical tool for respiratory system. Data Source: The English articles referred for this review paper were identified from various International peer reviewed journals indexed in Science citation index. Study Selection: 26 high quality articles most relevant to the highlighted topic which were published in last fifteen years were selected from almost 120 articles. Results: The analysis done and the outcome obtained by this computational method is as accurate as Spirometry and Pulmonary function test (PFT) result. CFD can be very useful in the cases where patents is unable to perform PFT. Pressure drop, Velocity profile, Wall shear stress & other flow parameter, respiratory resistance, Pattern of drug deposition, Particles transport/deposition, etc. had also been predicted accurately using CFD. The effect of tracheal stenosis on the flow parameters has been predicted. The size and location of tracheal stenosis has also been correlated with breathing difficulties. The distribution of air in various lobes of the lungs can be accurately predicted with CFD tool. Conclusion: Virtual surgery is eventually possible by using CFD after further research with validation. With the help of this multi - disciplinary and efficient tool we can obtain accurate result while reducing cost and time

Simulation of fluid dynamics and particle transport in realistic human airways

The aim of this research is to numerically study the flow characteristics and particle transport within human airways, specifically, the upper airways starting from the trachea to major bronchi. Different entering flow rates and frequencies are the major parameters varied in order to analyze the effect on particle deposition. There have been numerous flow-particle studies in human airways at the current level of knowledge, but one major contribution from this research is that realistic geometries of human airways are used to study flow-particle interaction, in which the airway models are reconstructed from computerized tomography (CT) data of real human tracheobronchial airways. CFD techniques for this particular study are developed based on the literature review of other similar studies. The k-omega turbulence model was found to be suitable for this type of study. Evaluation and validation of the numerical approach and results were carried out by comparing with other experimental studies in terms of geometrical details, lobar flow distribution in percentage of the tracheal flow, velocity profile, and deposition efficiency. This approach was found to be appropriate. Based on the developed techniques, two aerosol delivery methods used clinically were studied. Similarly, results were compared with experimental and theoretical results for validation. It was found that slower breathing gives better transportation into the lung periphery and faster breathing gives higher deposition rate in the first few generations of the tracheobronchial airways. Visualization techniques were also developed where deposition pattern provided easy-to-understand illustration to personnel with no engineerin g background. It showed that particles often concentrate along the carinal ridges at the bifurcations and inner walls leading down from carinal ridges. The study of the interaction between flow and particle described how skewed velocity profile and vortices in secondary velocity profile affected regional deposition efficiency as well as deposition pattern. The study also confirmed that right main bronchi usually capture more particles than left side as other researchers observed. Several important findings are summarized based on this research: • Stokes number although is a good indicator in providing regional deposition efficiency information, the local "hot-spots" still heavily rely on visualization of deposition pattern. • Generally speaking, high flow rate and/or large particle size lead to high deposition efficiency in the first bifurcation and cartilaginous rings along the trachea. • Bronchi in the right hand side usually capture more particles than bronchi in the left hand side. • Particles often concentrate along the carinal ridges at the bifurcations and inner walls leading down from carinal ridges. • In the aerosol delivery study, short inhalation and exhalation with small air volume gives lower deposition in the first six generations than long inhalation with large air volume. Therefore, if deposition into deeper locations of the lung is preferred, then slower breathing is required. On the contrary, if the treatment location is in the first few generations, then faster or moderate breathing is more ideal. • Deposition efficiency and deposition pattern can be estimated roughly from the velocity profile along the airway

Aerosol dynamics simulations of the anatomical variability of e-cigarette particle and vapor deposition in a stochastic lung

Electronic cigarette (EC) aerosols are typically composed of a mixture of nicotine, glycerine (VG), propylene glycol (PG), water, acidic stabilizers and a variety of flavors. Inhalation of e-cigarette aerosols is characterized by a continuous modification of particle diameters, concentrations, composition and phase changes, and smoker-specific inhalation conditions, i.e. puffing, mouthhold and bolus inhalation. The dynamic changes of inhaled e-cigarette droplets in the lungs due to coagulation, conductive heat and diffusive heat/convective vapor transport and particle phase chemistry are described by the Aerosol Dynamics in Containment (ADiC) model. For the simulation of the variability of inhaled particle and vapor deposition, the ADiC model is coupled with the IDEAL Monte Carlo code, which is based on a stochastic, asymmetric airway model of the human lung. We refer to the coupled model as "IDEAL/ADIC_v1.0". In this study, two different ecigarettes were compared, one without any acid ("no acid") and the other one with an acidic regulator (benzoic acid) to establish an initial pH level of about 7 ("lower pH"). Corresponding deposition patterns among human airways comprise total and compound-specific number and mass deposition fractions, distinguishing between inhalation and exhalation phases and condensed and vapor phases. Note that the inhaled EC aerosol is significantly modified in the oral cavity prior to inhalation into the lungs. Computed deposition fractions demonstrate that total particle mass is preferentially deposited in the alveolar region of the lung during inhalation. While nicotine deposits prevalently in the condensed phase for the "lower pH" case, vapor phase deposition is dominating the "no acid" case. The significant statistical fluctuations of the particle and vapor deposition patterns illustrate the inherent anatomical variability of the human lung structure.Peer reviewe

MODELING OF FLOW AND PARTICLE DYNAMICS HUMAN RESPIRATORY SYSTEM USING FLUID DYNAMICS

The aim of this research is to study numerically the flow characteristics and particle transport within a human respiratory system, including the human nasal cavity and the bifurcation. Various flow rates and particle sizes are main parameters varied in order to analyze the effects on particle movements and deposition on the human respiratory system. There are three main systems considered in this research: flow around a blockage in a channel, flow in the Final particle deposition with Stokes number, St = 0.12 for inlet flow rates of: (a) 30 L/min; (b) 60 L/min in human nasal cavity, and flow in the double bifurcation. Computational Fluid Dynamics (CFD) is used to solve gas-particle flow equations using a commercial software, FLUENT. Flow around a blockage in a channel was performed to gain confidence in the CFD model that has recirculation zone behind the block. The unsteady vortices flow around this blockage is investigated for Reynolds numbers, Re = 150, 300, 600, 900, and 1200 and Stokes numbers, St = 0.01, 0.1, 0.5, 1.0 and 2.0 by solving momentum and particle model equations. A detailed airflow structures such as vortices, flow distribution are obtained. It was found that the particle distribution depends on vortical structures and Stokes number. A model of real human nasal cavity is reconstructed from computerized tomography (CT) scans. The flow structure is validated with experimental data for flowrates of 7.5 L/min (Re = 1500) and 15 L/min (Re = 3000). The total particle deposition in nasal cavity is also validated with experimental data using inertial parameter. Then the model is further investigated the effect of turbulence on particle deposition with flowrates of 20, 30 and 40 L/min. Deposition was found to increase with Stoke number for the same Reynolds number. vii Three-dimensional double bifurcations with coplanar configurations are employed to investigate the flow. Results of laminar flow (Re = 500, Re = 1036, and Re = 2000) are used to compare with experimental and numerical solution for validation. The model is further used to investigate the turbulent flow and particle deposition for heavy breathing with flowrates of 30 L/min (Re = 7300) and 60 L/min (Re = 14600). It was found that the deposition efficiency is dependent on Reynolds number and Stokes numbers. This research outcome will guide to improve the injection particle drugs to human lungs and to develop nasal mask to protect the lungs from hazardous particles

Numerical modelling of airflow dynamics and particle deposition in human lungs

Research into airflow dynamics and particle transport in human lungs is receiving considerable attention from many researchers because of its significance for human health. Drug delivery through inhalation of air into the human lung is important to prevent/cure respiratory diseases. Many researchers have investigated the process of particle transport and deposition (TD) in the respiratory airway through analytical as well as numerical methods, during the last century. Nowadays, numerical methods are used to model various biomechanical engineering problems, including particle flow in the respiratory system. The greatest challenge in numerical modelling of particle TD is the complexity of human lungs. This thesis mainly focuses on developing numerical models and investigating the effectiveness of aerosol particle inhalation as drug delivery. Particle inhalation and deposition in human lungs is affected by the lung anatomy, breathing pattern and particle properties (Rissler et al. 2017). Therefore, airflow dynamics and inhaled aerosol particle transport in the lung airways are significant for human health; thus it is important to measure both the efficiency of inhaled drug therapy and the health implications of air pollution (Deng et al. 2018). Further, the lung airways become larger as people grow into adults, and the shape of the airway structure and breathing habits change. Therefore, aging is an important factor in respiratory health. Hence, a comprehensive age-specified particle TD study is necessary to better predict drug delivery to the targeted position in a human lung. This study aims to develop an advanced and efficient three-dimensional (3D) numerical model to analyse airflow characteristics and aerosol particle TD in human lungs. The model is used to analyse the contribution of fundamental impaction and diffusion mechanisms for nanoand microscale particle TD in age-specific terminal bronchiole airways. The outcomes of this study will help improve the effectiveness of delivery of drug aerosols into human lungs to treat obstructive lung diseases including asthma, lung cancer and COPD. In addition, the inhalation of different types of pollutant particles into human lungs is investigated further to understand the consequence of the pollution particle on lung health

Development of a rhesus monkey lung geometry model and application to particle deposition in comparison to humans

The exposure-dose-response characterization of an inhalation hazard established in an animal species needs to be translated to an equivalent characterization in humans relative to comparable doses or exposure scenarios. Here, the first geometry model of the conducting airways for rhesus monkeys is developed based upon CT images of the conducting airways of a 6-month-old male, rhesus monkey. An algorithm was developed for adding the alveolar region airways using published rhesus morphometric data. The resultant lung geometry model can be used in mechanistic particle or gaseous dosimetry models. Such dosimetry models require estimates of the upper respiratory tract volume of the animal and the functional residual capacity, as well as of the tidal volume and breathing frequency of the animal. The relationship of these variables to rhesus monkeys of differing body weights was established by synthesizing and modeling published data as well as modeling pulmonary function measurements on 121 rhesus control animals. Deposition patterns of particles up to 10 μm in size were examined for endotracheal and and up to 5 μm for spontaneous breathing in infant and young adult monkeys and compared to those for humans. Deposition fraction of respirable size particles was found to be higher in the conducting airways of infant and young adult rhesus monkeys compared to humans. Due to the filtering effect of the conducting airways, pulmonary deposition in rhesus monkeys was lower than that in humans. Future research areas are identified that would either allow replacing assumptions or improving the newly developed lung model

Numerical Analysis of Respiratory Aerosol Deposition: Effects of Exhalation, Airway Constriction and Electrostatic Charge

The dynamics of particle laden flows are integral to the analysis of toxic particle deposition and medical respiratory aerosol delivery. Computational fluid-particle dynamics (CFPD) can play a critical role in developing a better understanding of particle laden flows, especially in a number of under-explored areas. The applications considered in this study include both the numerical aspects and the physical phenomena of respiratory aerosol transport. Objective I: Considering the effects of mesh type and grid convergence, four commonly implemented mesh styles were applied to a double bifurcation respiratory geometry and tested for flow patterns and aerosol deposition. Results indicated that the mesh style employed had a significant effect on the transport and deposition of aerosols with hexahedral meshes being most accurate. Objective II: In order to evaluate the effects of bronchoconstriction under exhalation conditions, normal and constricted pediatric airway models were considered. Results include (i) a significant increase in deposition for constricted airways, and (ii) a novel correlation for deposition during exhalation based on the Dean and Stokes numbers. Objective IIIa: Considering evaluation of an aerosol size sampler, an eight-stage Andersen cascade impactor (ACI) was numerically analyzed. The numerical simulations indicated high non-uniformity and recirculation in the flow field. Numerical predictions of retention fraction matched well with existing experiments (0.5 11% error). Objective IIIb: As an extension to this study, numerical predictions of electrostatic charge effects on aerosol transport and deposition in the ACI were presented. Charges consistent with standard pharmaceutical pressurized metered dose inhalers and dry powder inhalers were considered. The numerical predictions indicated that charged aerosols deposit as if they were 5 85% larger due to electrostatic effects. Applications of the studies considered include (i) quantitative guidance in selecting numerical mesh styles and development of standard grid convergence criteria, (ii) the development of more accurate whole-lung deposition models that better evaluate exhalation conditions,(iii) improvements in the design of pharmaceutical assessment and delivery devices, and (vi) correction values to account for electrostatic charge on pharmaceutical aerosols

CFD modelling of air flow and fine powder deposition in the respiratory tract

This project was to investigate and observe characteristics of micro particles suspended in the ambient air or pharmaceutical aerosols with respect to the mechanisms of deposition in human airways under different inspiratory conditions. Such determination includes pattern observations of inspiratory flow-field of the air, particle trajectory during inspiratory conditions and particle deposition. Computational fluid dynamic (CFD) was employed to simulate above problems, aiming to observe flow-field of the inspiratory air and characteristic of flow turbulence in the respiratory tract as well as particle behaviour in the respiratory tract regarding to the particle deposition. In order to do so, three different airway models were employed for the simulations: two realistic airway models introduced by Kitaoka and Weibel airways model. The motion of micro-sized particles between 1~20 μm were simulated under the steady state two inlet-inspiratory conditions – inhalation condition (60 L/min) and breathing condition (18 L/min); to evaluate deposition efficiency. Inertial impaction was dominantly caused high density deposition of particles in upper tracheobronchial region, particularly in regions where daughter airways bifurcate. Results also showed that the velocity in the first bifurcation of airway was higher than the inlet velocity. Back pressures were been observed in lower generations, and high pressures were been observed at every bifurcation regions. The increase of velocity was observed where the fluid directions rapidly changed. Turbulence kinetic energy was the least in main bronchus of respiratory tract and fluctuated from generation to generation. In Kitaoka’s generation 0-7 model, deposition fractions of 2 μm, 6 μm and 10 μm particles were 6.6%, 60.7% and 91.5% respectively under inhalation condition whereas deposition fractions of such particles were 2.9%, 9.0% and 44.9% under breathing condition. In Kitaoka’s generation 0-11 model, deposition fractions of 2 μm, 6 μm and 10 μm particles were 30.9%, 80.1% and 99.8% respectively under inhalation condition whereas deposition fractions of such particles were 16.2%, 24.4% and 62.6% under breathing condition. Furthermore in Weibel’s generation 3-6 model, deposition fractions of 2 μm, 6 μm and 10 μm particles were 9.7%, 38.3% and 97.4% respectively under inhalation condition whereas deposition fractions of such particles were 3.2%, 15.6% and 56.2% under breathing condition

Unveiling advanced mechanisms of inhalable drug aerosol dynamics using computational fluid dynamics and discrete element method

Capsule-based dry powder inhalers (DPIs) are widely used to treat chronic obstructive pulmonary disease (COPD) by delivering active pharmaceutical ingredients (APIs) via inhalation into human respiratory systems. Previous research has shown that the actuation flow rate, aerodynamic particle size distribution (APSD), and particle shape of lactose carriers are factors that can influence the particle deposition patterns in human respiratory systems. Understanding the dynamics of APIs transport in DPIs and airways can provide significant value for the design optimization of DPIs and particle shapes to enhance the delivery of APIs to the designated lung sites, i.e., small airways. Thus, it is necessary to investigate how to modulate the above-mentioned factors to increase the delivery efficacy to small airways and enhance the therapeutic effect to treat COPD. Compared with in vitro and in vivo methods, computational fluid-particle dynamics (CFPD) models allow researchers to study the transport dynamics of inhalable therapeutic dry powders in both DPI and human respiratory systems. However, existing CFPD models neglect particle-particle interactions, and most existing airway models lack peripheral lung airway and neglect the airway deformation kinematics. Such deficiencies can lead to inaccurate predictions of particle transport and deposition. This study developed a one-way coupled computational fluid dynamics (CFD) and discrete element method (DEM) model to simulate the particle-particle and particle-device interactions, and the transport of API-carrier dry powder mixtures with different shapes of carriers in a DPI flow channel. The influence of actuation flow rate (30 to 90 L/min) and particle shape (aspect ratio equals 1, 5, and 10) on lactose carrier dynamics in a representative DPI, i.e., SpirivaTM HandihalerTM, has been investigated. Subsequently, an elastic truncated whole-lung model has also been developed to predict particle transport and deposition from mouth to alveoli, with disease-specific airway deformation kinematics. Numerical results indicate that 90 L/min actuation flow rate generates the highest delivery efficiency of Handihaler, as approximately 26% API reaches the deep lung region. The elastic truncated whole-lung modeling results show that noticeable differences of predictions between static and elastic lung models can be found, which demonstrates the necessity to model airway deformation kinematics in virtual lung models