Aerosols in Healthy and Emphysematous In Silico Pulmonary Acinar Rat Models

International audienceThere has been relatively little attention given on predicting particle deposition in the respiratory zone of the diseased lungs despite the high prevalence of chronic obstructive pulmonary disease (COPD). Increased alveolar volume and deterioration of alveolar septum, characteristic of emphysema, may alter the amount and location of particle deposition compared to healthy lungs, which is particularly important for toxic or therapeutic aerosols. In an attempt to shed new light on aerosol transport and deposition in emphysematous lungs, we performed numerical simulations in models of healthy and emphysematous acini motivated by recent experimental lobar-level data in rats~\citep{OakesEmp}. Compared to healthy acinar structures, models of emphysematous subacini were created by removing inter-septal alveolar walls and enhancing the alveolar volume in either a homogeneous or heterogeneous fashion. Flow waveforms and particle properties were implemented to match the experimental data. The occurrence of flow separation and recirculation within alveolar cavities was found in proximal generations of the healthy zones, in contrast to the radial-like airflows observed in the diseased regions. In agreement with experimental data, simulations point to particle deposition concentrations that are more heterogeneously distributed in the diseased models compared with the healthy one. Yet, simulations predicted less deposition in the emphysematous models in contrast to some experimental studies, a likely consequence due to the shallower penetration depths and modified flow topologies in disease compared to health. These spatial-temporal particle transport simulations provide new insight on deposition in the emphysematous acini and shed light on experimental observations

Biomedical and biophysical limits to mathematical modeling of pulmonary system mechanics: a scoping review on aerosol and drug delivery.

Undoubtedly, the construction of the biomechanical geometry systems with the help of computer tomography (CT) and magnetic resonance imaging (MRI) has made a significant advancement in studying in vitro numerical models as accurately as possible. However, some simplifying assumptions in the computational studies of the respiratory system have caused errors and deviations from the in vivo actual state. The most important of these hypotheses is how to generate volume from the point cloud exported from CT or MRI images, not paying attention to the wall thickness and its effect in computational fluid dynamic method, statistical logic of aerosol trap in software; and most importantly, the viscoelastic effect of respiratory tract wall in living tissue pointed in the fluid-structure interaction method. So that applying the viscoelastic dynamic mesh effect in the form of the moving deforming mesh can be very effective in achieving more appropriate response quality. Also, changing the volume fraction of the pulmonary extracellular matrix constituents leads to changes in elastic modulus (storage modulus) and the viscous modulus (loss modulus) of lung tissue. Therefore, in the biomedical computational methods where the model wall is considered flexible, the viscoelastic properties of the texture must be considered correctly

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

Structure of the distal lung studied with inhaled nanoparticles

Techniques able to detect impairments in the distal human lung are lacking. Since inhaled nanoparticles are predominantly deposited in the acini, their deposition can be used to derive structural properties of the region. Intheory, structural enlargements in the distal lung imply that less inhaled nanoparticles deposit there. This rationale is the basis of the airspace dimension assessment (AiDA) method. The research presented in this thesis aimed to evaluate and characterize this new method for the measurement of distal lung structure. The objective was to do so by comparing the AiDA method with other lung structure and lung function measuring techniques as well as with background variables. AiDA measurements were carried out with nearly 800 individuals in four different studies. From these, distal airspace radii (rAiDA) were calculated, along with a second index: zero seconds recovery R0.The AiDA method was benchmarked against magnetic resonance imaging (MRI) with hyperpolarized gas, with 23 healthy individuals and compared to computed tomography (CT) variables and standard pulmonary function tests (PFTs) in a population-based cohort with 695 subjects. The method was also evaluated as a tool to detect lung changes in an occupational group exposed to high loads of air pollution (with 28 welders and 17 controls), and AiDA indices were evaluated as parameters that can explain observed discrepancies between modeled and measured respiratory tract particle deposition in a group of 17 healthy participants.The measured rAiDA were correlated with lung microstructure measurements obtained with MRI with hyperpolarized gas and rAiDA were on average larger in subjects with emphysema detected with CT, in comparison with healthy participants. The AiDA indices explained variance that no other PFTs captured, but there was no average difference between the occupational group and controls measurable with the AiDA method. The rAiDA were correlated with the difference between measured and modeled respiratory tract particle deposition. Moreover, rAiDA increased with age, but the inter-subject variability was large in all age groups. The results demonstrated that the AiDA method has potential to characterize distal lung structure and may serve as a new, non-invasive tool for clinical examination of human lungs. However, the R0 index needs to be furtherevaluated. In the future, controlled clinical trials are necessary to evaluate the method’s sensitivity to different lung conditions

Toxicity of lunar dust

The formation, composition and physical properties of lunar dust are incompletely characterised with regard to human health. While the physical and chemical determinants of dust toxicity for materials such as asbestos, quartz, volcanic ashes and urban particulate matter have been the focus of substantial research efforts, lunar dust properties, and therefore lunar dust toxicity may differ substantially. In this contribution, past and ongoing work on dust toxicity is reviewed, and major knowledge gaps that prevent an accurate assessment of lunar dust toxicity are identified. Finally, a range of studies using ground-based, low-gravity, and in situ measurements is recommended to address the identified knowledge gaps. Because none of the curated lunar samples exist in a pristine state that preserves the surface reactive chemical aspects thought to be present on the lunar surface, studies using this material carry with them considerable uncertainty in terms of fidelity. As a consequence, in situ data on lunar dust properties will be required to provide ground truth for ground-based studies quantifying the toxicity of dust exposure and the associated health risks during future manned lunar missions.Comment: 62 pages, 9 figures, 2 tables, accepted for publication in Planetary and Space Scienc

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