Airway stability in sleep apnea: Assessing continuous positive airway pressure efficiency.

Obstructive Sleep Apnea Syndrome (OSAS) disrupts millions of lives with its burden of airway obstruction during sleep. Continuous Positive Airway Pressure (CPAP) therapy has been scrutinized for its biomechanical impact on the respiratory tract. This study leverages computational fluid dynamics to investigate CPAP's effects at 9 cm H2O (882.6 Pa) on the computed-tomography-based nasal-to-14-generation full respiratory tract model compared to ambient conditions, focusing on static pressure, airflow velocity, and shear stress. Our findings reveal that CPAP significantly increases static pressure, enhancing airway patency without adverse changes in airflow velocity or harmful shear stress on lung tissue, challenging prior concerns about its safety. Notably, the larynx experiences the highest shear stress due to its narrow anatomy, yet CPAP therapy overall supports airway walls against collapse. This investigation highlights CPAP's critical role in OSAS treatment, offering reassurance about its safety and efficacy. By clarifying CPAP therapy's physiological impacts, our study contributes vital insights for optimizing OSAS management strategies, affirming CPAP's benefit in maintaining open airways with minimal tissue strain.

Effect of microplastics deposition on human lung airways: A review with computational benefits and challenges.

Microplastics have become omnipresent in the environment, including the air we inhale, the water we consume, and the food we eat. Despite limited research, the accumulation of microplastics within the human respiratory system has garnered considerable interest because of its potential implications for health. This review offers a comprehensive examination of the impacts stemming from the accumulation of microplastics on human lung airways and explores the computational benefits and challenges associated with studying this phenomenon. The existence of microplastics in the respiratory system can lead to a range of adverse effects. Research has indicated that microplastics can induce inflammation, oxidative stress, and impaired lung function. Furthermore, the small size of microplastics allows them to penetrate deep into the lungs, reaching the alveoli, where gas exchange takes place. This raises concerns about long-term health consequences, such as the development of respiratory diseases and the potential for translocation to other organs. Computational approaches have been instrumental in understanding the impact of microplastic deposition on human lung airways. Computational models and simulations enable the investigation of particle dynamics, deposition patterns, and interaction mechanisms at various levels of complexity. However, studying microplastics in the lung airways using computational methods presents several challenges. The complex anatomy and physiological processes of the respiratory system require accurate representation in computational models. Obtaining relevant data for model validation and parameterization remains a significant hurdle. Additionally, the diverse nature of microplastics, including variations in size, shape, and chemical composition, poses challenges in capturing their full range of behaviours and potential toxicological effects.

The concentration-dependent effect of hydrocortisone on the structure of model lung surfactant monolayer by using an in silico approach.

Understanding the adsorption mechanism of corticosteroids in the lung surfactant requires the knowledge of corticosteroid molecular interactions with lung surfactant monolayer (LSM). We employed coarse-grained molecular dynamics simulation to explore the action of hydrocortisone on an LSM comprised of a phospholipid, cholesterol and surfactant protein. The structural and dynamical morphology of the lung surfactant monolayer at different surface tensions were investigated to assess the monolayer compressibility. The simulations were also conducted at the two extreme ends of breathing cycles: exhalation (0 mN m-1 surface tension) and inhalation (20 mN m-1 surface tension). The impact of surface tension and hydrocortisone concentration on the monolayer compressibility and stability are significant, resulting the monolayer expansion at higher surface tension. However, at low surface tension, the highly compressed monolayer induces monolayer instability in the presence of the drug due to the accumulation of surfactant protein and drug. The constant area per lipid simulation results demonstrate that the surface pressure-area isotherms show a decrease in area-per-lipid with increased drug concentration. The drug-induced expansion causes considerable instability in the monolayer after a specific drug concentration is attained at inhalation breathing condition, whereas, for exhalation breathing, the monolayer gets more compressed, causing the LSM to collapse. The monolayer collapse occurs for inhalation due to the higher drug concentration, whereas for exhalation due to the accumulation of surfactant proteins and drugs. The findings from this study will aid in enhancing the knowledge of molecular interactions of corticosteroid drugs with lung surfactants to treat respiratory diseases.

Surface tension effects on flow dynamics and alveolar mechanics in the acinar region of human lung.

Background: Computational fluid dynamics (CFD) simulations, in-vitro setups, and experimental ex-vivo approaches have been applied to numerous alveolar geometries over the past years. They aimed to study and examine airflow patterns, particle transport, particle propagation depth, particle residence times, and particle-alveolar wall deposition fractions. These studies are imperative to both pharmaceutical and toxicological studies, especially nowadays with the escalation of the menacing COVID-19 virus. However, most of these studies ignored the surfactant layer that covers the alveoli and the effect of the air-surfactant surface tension on flow dynamics and air-alveolar surface mechanics. Methods: The present study employs a realistic human breathing profile of 4.75s for one complete breathing cycle to emphasize the importance of the surfactant layer by numerically comparing airflow phenomena between a surfactant-enriched and surfactant-deficient model. The acinar model exhibits physiologically accurate alveolar and duct dimensions extending from lung generations 18 to 23. Airflow patterns in the surfactant-enriched model support previous findings that the recirculation of the flow is affected by its propagation depth. Proximal lung generations experience dominant recirculating flow while farther generations in the distal alveolar region exhibit dominant radial flows. In the surfactant-enriched model, surface tension values alternate during inhalation and exhalation, with values increasing to 25 mN/m at the inhalation and decreasing to 1 mN/m at the end of the exhalation. In the surfactant-deficient model, only water coats the alveolar walls with a high surface tension value of 70 mN/m. Results: Results showed that surfactant deficiency in the alveoli adversely alters airflow behavior and generates unsteady chaotic breathing through the production of vorticities, accompanied by higher vorticity magnitudes (100% increase at the end of exhalation) and higher velocity magnitudes (8.69% increase during inhalation and 11.9% increase during exhalation). In addition, high air-water surface tension in the surfactant-deficient case was found to induce higher shear stress values (by around a factor of 10) on the alveolar walls than that of the surfactant-enriched case. Conclusion: Overall, it was concluded that the presence of the surfactant improves respiratory mechanics and allows for smooth breathing and normal respiration.

Nanoparticle transport and deposition in a heterogeneous human lung airway tree: An efficient one path model for CFD simulations.

Understanding nano-particle inhalation in human lung airways helps targeted drug delivery for treating lung diseases. A wide range of numerical models have been developed to analyse nano-particle transport and deposition (TD) in different parts of airways. However, a precise understanding of nano-particle TD in large-scale airways is still unavailable in the literature. This study developed an efficient one-path numerical model for simulating nano-particle TD in large-scale lung airway models. This first-ever one-path numerical approach simulates airflow and nano-particle TD in generations 0-11 of the human lung, accounting for 93% of the whole airway length. The one-path model enables the simulation of particle TD in many generations of airways with an affordable time. The particle TD of 5 nm, 10 nm and 20 nm particles is simulated at inhalation flow rates for two different physical activities: resting and moderate activity. It is found that particle deposition efficiency of 5 nm particles is 28.94% higher than 20 nm particles because of the higher dispersion capacity. It is further proved that the diffusion mechanism dominates the particle TD in generations 0-11. The deposition efficiency decreases with the increase of generation number irrespective of the flow rate and particle size. The effects of the particle size and flow rate on the escaping rate of each generation are opposite to the corresponding effects on the deposition rate. The quantified deposition and escaping rates at generations 0-11 provide valuable guidelines for drug delivery in human lungs.

Molecular basis of transport of surface functionalised gold nanoparticles to pulmonary surfactant.

Ligands like alkanethiol (e.g. dodecanethiol, hexadecanethiol, etc.) and polymers (e.g. poly(vinyl pyrrolidone), polyethylene glycol-thiol) capped to the gold nanoparticles (AuNPs) are widely used in biomedical field as drug carriers and as promising materials for probing and manipulating cellular processes. Ligand functionalised AuNPs are known to interact with the pulmonary surfactant (PS) monolayer once reaching the alveolar region. Therefore, it is crucial to understand the interaction between AuNPs and PS monolayers. Using coarse-grained molecular dynamics simulations, the effect of ligand density, and ligand length have been studied for two classes of ligands on a PS model monolayer consisting of DPPC, POPG, cholesterol and SP-B (mini-peptide). The ligands considered in this study are alkanethiol and polyethylene glycol (PEG) thiol as examples of hydrophobic and hydrophilic ligands, respectively. It was observed that the interaction between AuNPs and PS changes the biophysical properties of PS monolayer in compressed and expanded states. The AuNPs with hydrophilic ligand, can penetrate through the monolayer more easily, while the AuNPs with hydrophobic ligand are embedded in the monolayer and participated in deforming the monolayer structure particularly the monolayer in the compressed state. The bare AuNPs hinder to lower the monolayer surface tension value at the interface, however introducing ligand to the bare AuNPs or increasing the ligand length and density have an impact of lowering of monolayer surface tension to a minor extent. The simulation results guide the design of ligand protected NPs as drug carriers and can identify the nanoparticles' potential side effects on lung surfactant.

Recent advances in lung-on-a-chip models.

With the global burden of respiratory diseases, rapid identification of the best therapeutic measures to combat these diseases is essential. Animal models and 2D cell culture models do not replicate the findings observed in vivo. To gain deeper insight into lung pathology and physiology, 3D and advanced lung-on-a-chip models have been developed recently. Lung-on-a-chip models more accurately simulate the lung's microenvironment and functions in vivo, resulting in more-accurate assessments of drug safety and effectiveness. This review discusses the transition from 2D to 3D models and the recent advances in lung-on-a-chip platforms, their implementation and the numerous challenges faced. Finally, a general overview of this platform and its potential applications in respiratory disease research and drug discovery is highlighted.

Is the SARS CoV-2 Omicron Variant Deadlier and More Transmissible Than Delta Variant?

Genetic variants of severe acute respiratory syndrome coronavirus (SARS-CoV-2) have been globally surging and devastating many countries around the world. There are at least eleven reported variants dedicated with inevitably catastrophic consequences. In 2021, the most dominant Delta and Omicron variants were estimated to lead to more severity and deaths than other variants. Furthermore, these variants have some contagious characteristics involving high transmissibility, more severe illness, and an increased mortality rate. All outbreaks caused by the Delta variant have been rapidly skyrocketing in infection cases in communities despite tough restrictions in 2021. Apart from it, the United States, the United Kingdom and other high-rate vaccination rollout countries are still wrestling with this trend because the Delta variant can result in a significant number of breakthrough infections. However, the pandemic has changed since the latest SARS-CoV-2 variant in late 2021 in South Africa, Omicron. The preliminary data suggest that the Omicron variant possesses 100-fold greater than the Delta variant in transmissibility. Therefore, this paper aims to review these characteristics based on the available meta-data and information from the first emergence to recent days. Australia and the five most affected countries, including the United States, India, Brazil, France, as well as the United Kingdom, are selected in order to review the transmissibility, severity and fatality due to Delta and Omicron variants. Finally, the vaccination programs for each country are also reviewed as the main factor in prevention.

Concentration-Dependent Effect of the Steroid Drug Prednisolone on a Lung Surfactant Monolayer.

The lung surfactant monolayer (LSM) is the main barrier for particles entering the lung, including steroid drugs used to treat lung diseases. The present study combines Langmuir experiments and coarse-grained (CG) molecular dynamics simulations to investigate the concentration-dependent effect of steroid drug prednisolone on the structure and morphology of a model LSM. The surface pressure-area isotherms for the Langmuir monolayers reveal a concentration-dependent decrease in area per lipid (APL). Results from simulations at a fixed surface tension, representing inhalation and exhalation conditions, suggest that at high drug concentrations, prednisolone induces a collapse of the LSM, which is likely caused by the inability of the drug to diffuse into the bilayer. Overall, the monolayer is most susceptible to drug-induced collapse at surface tensions representing exhalation conditions. The presence of cholesterol also exacerbates the instability. The findings of this investigation might be helpful for better understanding the interaction between steroid drug prednisolone and lung surfactants in relation to off-target effects.

Drug Meets Monolayer: Understanding the Interactions of Sterol Drugs with Models of the Lung Surfactant Monolayer Using Molecular Dynamics Simulations.

The lung surfactant monolayer (LSM) is a thin layer of lipids and proteins that forms the air/water interface of the alveoli. The primary function of the LSM is to reduce the surface tension at the air/water interface during breathing. The LSM also forms the main biological barrier for any inhaled particles, including drugs, to treat lung diseases. Elucidating the mechanism by which these drugs bind to and absorb into the LSM requires a molecular-level understanding of any drug-induced changes to the morphology, structure, and phase changes of the LSM.Molecular dynamics simulations have been used extensively to study the structure and dynamics of the LSM. The monolayer is usually simulated in at least two states: the compressed state, mimicking exhalation, and the expanded state, mimicking inhalation. In this chapter, we provide detailed instructions on how to set up, run, and analyze coarse-grained MD simulations to study the concentration-dependent effect of a sterol drug on the LSM, both in the expanded and compressed state.

The steroid mometasone alters protein containing lung surfactant monolayers in a concentration-dependent manner.

Mometasone is an investigational anti-inflammatory steroidal drug to treat inflammation via pulmonary administration. For steroid drugs to be effective they need to be adsorbed by lung surfactants, a thin monolayer at the air-water interface in alveoli that reduces surface tension. Information on the molecular-level interactions of the drug with lung surfactants is useful to understand the mechanism of adsorption. In this study, we use coarse-grained molecular dynamics simulation to understand the concentration-dependent effect of mometasone on a lung surfactant monolayer (LSM) composed of lipids and surfactant proteins, under two different breathing conditions (exhalation, at surface tension 0 mNm-1 and inhalation, surface tension 20-25 mNm-1). A series of fixed-APL and fixed-surface tension simulations were used to demonstrate that in the absence of drugs, the model LSM reproduces the surface tensions for the compressed and expanded states, as well as compressibility at different surface tensions. In-depth analysis of simulations of a LSM in the presence of five different drug concentrations shows that mometasone alters the structure and dynamics of the LSM in a concentration-dependent manner. Mometasone induces a collapse in the monolayer that is affected by the surfactant protein and surface tension. Overall, these findings suggest that the surfactant proteins, surface tension and drug concentration are all critical components affecting monolayer stability and drug adsorption. The outcomes of this study may be beneficial for a more in-depth understanding of how mometasone is adsorbed by lung surfactants.

Phenolic compounds alter the ion permeability of phospholipid bilayers via specific lipid interactions.

This study aims to understand the role of specific phenolic-lipid interactions in the membrane-altering properties of phenolic compounds. We combine tethered lipid bilayer (tBLM) electrical impedance spectroscopy (EIS) with all-atom molecular dynamics (MD) simulations to study the membrane interactions of six phenolic compounds: caffeic acid methyl ester, caffeic acid, 3,4 dihydroxybenzoic acid, chlorogenic acid, syringic acid and p-coumaric acid. tBLM/EIS experiments showed that caffeic acid methyl ester, caffeic acid and 3,4 dihydroxybenzoic acid significantly increase the permeability of phospholipid bilayers to Na+ ions. In contrast, chlorogenic acid, syringic acid and p-coumaric acid showed no effect. Experiments with lipids lacking the phosphate group show a significant decrease in the membrane-altering effects indicating that specific phenolic-lipid interactions are critical in altering ion permeability. MD simulations confirm that compounds that alter ion permeability form stable interactions with the phosphate oxygen. In contrast, inactive phenolic compounds are superficially bound to the membrane surface and primarily interact with interfacial water. Our combined results show that compounds with similar structures can have very different effects on ion permeability in membranes. These effects are governed by specific interactions at the water-lipid interface and show no correlation with lipophilicity. Furthermore, none of the compounds alter the overall structure of the phospholipid bilayer as determined by area per lipid and order parameters. Based on data from this study and previous findings, we propose that phenolic compounds can alter membrane ion permeability by causing local changes in lipid packing that subsequently reduce the energy barrier for ion-induced pores.

Shape matters-the interaction of gold nanoparticles with model lung surfactant monolayers.

The lung surfactant monolayer (LSM) forms the main biological barrier for any inhaled particles to enter our bloodstream, including gold nanoparticles (AuNPs) present as air pollutants and under investigation for use in biomedical applications. Understanding the interaction of AuNPs with lung surfactant can assist in understanding how AuNPs enter our lungs. In this study, we use coarse-grained molecular dynamics simulations to investigate the effect of four different shape D AuNPs (spherical, box, icosahedron and rod) on the structure and dynamics of a model LSM, with a particular focus on differences resulting from the shape of the AuNP. Monolayer-AuNP systems were simulated in two different states: the compressed state and the expanded state, representing inhalation and exhalation conditions, respectively. Our results indicate that the compressed state is more affected by the presence of the AuNPs than the expanded state. Our results show that in the compressed state, the AuNPs prevent the monolayer from reaching the close to zero surface tension required for normal exhalation. In the compressed state, all four nanoparticles (NPs) reduce the lipid order parameters and cause a thinning of the monolayer where the particles drag surfactant molecules into the water phase. Comparing the different properties shows no trend concerning which shape has the biggest effect on the monolayer, as shape-dependent effects vary among the different properties. Insights from this study might assist future work of how AuNP shapes affect the LSM during inhalation or exhalation conditions.

Topological Optimization of Auxetic Coronary Stents Considering Hemodynamics.

This paper is to design a new type of auxetic metamaterial-inspired structural architectures to innovate coronary stents under hemodynamics via a topological optimization method. The new architectures will low the occurrence of stent thrombosis (ST) and in-stent restenosis (ISR) associated with the mechanical factors and the adverse hemodynamics. A multiscale level-set approach with the numerical homogenization method and computational fluid dynamics is applied to implement auxetic microarchitectures and stenting structure. A homogenized effective modified fluid permeability (MFP) is proposed to efficiently connect design variables with motions of blood flow around the stent, and a Darcy-Stokes system is used to describe the coupling behavior of the stent structure and fluid. The optimization is formulated to include three objectives from different scales: MFP and auxetic property in the microscale and stenting stiffness in the macroscale. The design is numerically validated in the commercial software MATLAB and ANSYS, respectively. The simulation results show that the new design can not only supply desired auxetic behavior to benefit the deliverability and reduce incidence of the mechanical failure but also improve wall shear stress distribution to low the induced adverse hemodynamic changes. Hence, the proposed stenting architectures can help improve safety in stent implantation, to facilitate design of new generation of stents.

How severe acute respiratory syndrome coronavirus-2 aerosol propagates through the age-specific upper airways.

The recent outbreak of the COVID-19 causes significant respirational health problems, including high mortality rates worldwide. The deadly corona virus-containing aerosol enters the atmospheric air through sneezing, exhalation, or talking, assembling with the particulate matter, and subsequently transferring to the respiratory system. This recent outbreak illustrates that the severe acute respiratory syndrome (SARS) coronavirus-2 is deadlier for aged people than for other age groups. It is evident that the airway diameter reduces with age, and an accurate understanding of SARS aerosol transport through different elderly people's airways could potentially help the overall respiratory health assessment, which is currently lacking in the literature. This first-ever study investigates SARS COVID-2 aerosol transport in age-specific airway systems. A highly asymmetric age-specific airway model and fluent solver (ANSYS 19.2) are used for the investigation. The computational fluid dynamics measurement predicts higher SARS COVID-2 aerosol concentration in the airway wall for older adults than for younger people. The numerical study reports that the smaller SARS coronavirus-2 aerosol deposition rate in the right lung is higher than that in the left lung, and the opposite scenario occurs for the larger SARS coronavirus-2 aerosol rate. The numerical results show a fluctuating trend of pressure at different generations of the age-specific model. The findings of this study would improve the knowledge of SARS coronavirus-2 aerosol transportation to the upper airways which would thus ameliorate the targeted aerosol drug delivery system.

Polydisperse Aerosol Transport and Deposition in Upper Airways of Age-Specific Lung.

A comprehensive understanding of airflow characteristics and particle transport in the human lung can be useful in modelling to inform clinical diagnosis, treatment, and management, including prescription medication and risk assessment for rehabilitation. One of the difficulties in clinical treatment of lung disorders lies in the patients' variable physical lung characteristics caused by age, amongst other factors, such as different lung sizes. A precise understanding of the comparison between different age groups with various flow rates is missing in the literature, and this study aims to analyse the airflow and aerosol transport within the age-specific lung. ANSYS Fluent solver and the large-eddy simulation (LES) model were employed for the numerical simulation. The numerical model was validated with the available literature and the computational results showed airway size-reduction significantly affected airflow and particle transport in the upper airways. This study reports higher deposition at the mouth-throat region for larger diameter particles. The overall deposition efficiency (DE) increased with airway size reduction and flow rate. Lung aging effected the pressure distribution and a higher pressure drop was reported for the aged lung as compared to the younger lung. These findings could inform medical management through individualised simulation of drug-aerosol delivery processes for the patient-specific lung.

SARS CoV-2 aerosol: How far it can travel to the lower airways?

The recent outbreak of the SARS CoV-2 virus has had a significant effect on human respiratory health around the world. The contagious disease infected a large proportion of the world population, resulting in long-term health issues and an excessive mortality rate. The SARS CoV-2 virus can spread as small aerosols and enters the respiratory systems through the oral (nose or mouth) airway. The SARS CoV-2 particle transport to the mouth-throat and upper airways is analyzed by the available literature. Due to the tiny size, the virus can travel to the terminal airways of the respiratory system and form a severe health hazard. There is a gap in the understanding of the SARS CoV-2 particle transport to the terminal airways. The present study investigated the SARS CoV-2 virus particle transport and deposition to the terminal airways in a complex 17-generation lung model. This first-ever study demonstrates how far SARS CoV-2 particles can travel in the respiratory system. ANSYS Fluent solver was used to simulate the virus particle transport during sleep and light and heavy activity conditions. Numerical results demonstrate that a higher percentage of the virus particles are trapped at the upper airways when sleeping and in a light activity condition. More virus particles have lung contact in the right lung than the left lung. A comprehensive lobe specific deposition and deposition concentration study was performed. The results of this study provide a precise knowledge of the SARs CoV-2 particle transport to the lower branches and could help the lung health risk assessment system.

Computational Studies of Lipid-Wrapped Gold Nanoparticle Transport Through Model Lung Surfactant Monolayers.

Colloidal nanoparticles, such as gold nanoparticles (AuNPs), are promising materials for the delivery of hydrophilic drugs via the pulmonary route. The inhaled nanoparticle drug carriers primarily deposit in lung alveoli and interact with the alveolar surface known as lung surfactants. Therefore, it is vital to understand the interactions of nanocarriers with the surfactant layer. To understand the interactions at the molecular level, here we simulated model lung surfactant monolayers with phospholipid (PL)-wrapped AuNPs at the vacuum-water interface using coarse-grained molecular dynamics simulations. The PL-wrapped AuNPs quickly adsorbed into the surfactant layer, altered the structural properties of the monolayer, and at high concentrations initiated the compressed monolayer to collapse/buckle. Among the surfactant monolayer lipid components, cholesterol adsorbed to the AuNPs preferentially over PL species. The position of the adsorbed PL-AuNPs within the monolayer, and subsequent monolayer perturbation, vary depending on the monolayer phase, monolayer composition, and species of PL used as a ligand. Information provided by these molecular dynamic simulations helps to rationalize why some colloidal nanoparticles work better as nanocarriers than others and aid the design of new ones, to avoid biological toxicity and improve efficacy for pulmonary drug delivery.

The role of SP-B1-25 peptides in lung surfactant monolayers exposed to gold nanoparticles.

Lung surfactant (LS) monolayers that continuously expand and compress during breathing cycles, act as the first line barrier for inhaled nanoparticles. It is known that nanoparticles which adsorb to the surface of the surfactant layer facilitate the rearrangement of lipids and peptides at various stages of the breathing cycle. However, the structural mechanisms for this ability of the lipid rearrangement are not yet fully understood. Coarse-grained molecular dynamics simulations are performed to investigate the role of surfactant protein B (SP-B) segments (SP-B1-25) in modulating the biophysical properties of the surfactant monolayer in the presence of polydisperse gold nanoparticles (AuNPs) at different concentrations. Herein, we observe that the AuNPs significantly alter the inherent structural and dynamical properties of the monolayer and its components in three different breathing states. When adsorbed into the monolayer, the AuNPs inhibit the ability of the monolayer to recover its surface tension and other properties. The presence of SP-B1-25 in the monolayer accelerates the diffusion of the monolayer phospholipids, contrarily to the role of AuNPs on phospholipid diffusion. Also, the AuNPs and the peptides in the monolayer significantly increase their agglomeration in the presence of one another. Overall, the simulations predict that the presence of polydisperse AuNPs hampers the stability and biophysical functions of the LS in contrast to the role of the peptide. This study provides a clear view of the hydrophobic peptide role in the LS monolayer at the interface along with the interactions and the translocation of AuNPs that could have a significant impact to assess the NPs inhalation.

Helium-Oxygen Mixture Model for Particle Transport in CT-Based Upper Airways.

The knowledge of respiratory particle transport in the extra-thoracic pathways is essential for the estimation of lung health-risk and optimization of targeted drug delivery. The published literature reports that a significant fraction of the inhaled aerosol particles are deposited in the upper airways, and available inhalers can deliver only a small amount of drug particles to the deeper airways. To improve the targeted drug delivery efficiency to the lungs, it is important to reduce the drug particle deposition in the upper airways. This study aims to minimize the unwanted aerosol particle deposition in the upper airways by employing a gas mixture model for the aerosol particle transport within the upper airways. A helium-oxygen (heliox) mixture (80% helium and 20% oxygen) model is developed for the airflow and particle transport as the heliox mixture is less dense than air. The mouth-throat and upper airway geometry are extracted from CT-scan images. Finite volume based ANSYS Fluent (19.2) solver is used to simulate the airflow and particle transport in the upper airways. Tecplot software and MATLAB code are employed for the airflow and particle post-processing. The simulation results show that turbulence intensity for heliox breathing is lower than in the case of air-breathing. The less turbulent heliox breathing eventually reduces the deposition efficiency (DE) at the upper airways than the air-breathing. The present study, along with additional patient-specific investigation, could improve the understanding of particle transport in upper airways, which may also increase the efficiency of aerosol drug delivery.