EDITORIAL article Front. Vet. Sci., 25 March 2024Sec. Comparative and Clinical Medicine Volume 11 - 2024 | https://doi.org/10.3389/fvets.2024.1390136

Feline lower airway disease comprises a spectrum of inflammatory conditions, including asthma, which is commonly treated with inhaled glucocorticoids. This study employs computed tomography (CT)-based computational fluid dynamics (CFD) models to characterize airflow dynamics in feline lower airways with and without bronchial disease (BD and NBD), evaluating velocity, pressure, wall shear stress, and airway resistance under different flow conditions. In addition, deposition patterns of two aerosol particle sizes (1 µm and 10 µm) were assessed within the trachea and bronchi. Geometrical reconstructions of the trachea and lobar bronchi were generated from CT scans of 24 cats, classified into BD and NBD groups. Simulations were performed using two airflow conditions and two particle diameters. Airflow parameters and aerosol particle deposition were calculated for each model. A trend toward higher values of most airflow parameters was observed in the NBD group, except for expiratory resistance and velocity. However, no statistically significant differences in airflow parameters were identified between groups. Particle deposition analysis showed a higher deposition fraction for larger particles, with 10 µm particles depositing more frequently on bronchial walls than 1 µm particles in both groups. Overall, CT-based CFD analysis revealed no significant group differences in resistance, pressure, wall shear stress, or velocity. Nevertheless, particle size influenced deposition patterns, with larger particles showing increased bronchial trapping. Although the initial hypothesis was not confirmed, this feasibility and characterization study establishes a methodological framework for future in silico investigations of feline lower airway disease providing preliminary physiologically and clinically relevant insights.

Current airway stents, including silicone and metallic devices, remain associated with important complications such as migration, restenosis, mucus retention and the need for repeated interventions. Biodegradable stents offer a promising alternative by providing temporary mechanical support while avoiding the long-term presence of a permanent implant. However, the influence of stent geometry and material properties on their mechanical performance and interaction with airway tissue is still not fully understood. This study presents a computational framework integrating computer-aided design and finite element analysis to investigate the mechanical behaviour of biodegradable tracheobronchial stents. Two stent architectures (X-pattern and W-pattern) were analysed over a range of wire thicknesses using two biodegradable materials: a PLA/PCL; 70/30 wt.% blend and AZ31 magnesium alloy. Radial compression, diameter recovery after radial compression and stent–tissue interaction simulations were performed to evaluate the influence of geometry, material selection and design parameters on device performance. The results suggested that both stent geometry and material properties strongly influence the mechanical behaviour of biodegradable airway stents, although they affect different aspects of the stent–tissue interaction. The X-pattern consistently exhibited greater resistance to radial compression, lower elastic diameter recovery after radial compression and improved maintenance of the expanded lumen compared with the W-pattern. Material properties primarily affected the magnitude of the mechanical response, as further confirmed by the quantitative contact-pressure analysis, with AZ31 providing greater radial support, while the spatial distributions of stress and strain within the tracheal wall were mainly governed by the stent architecture. Based on the computational analyses, X-pattern stents manufactured from the PLA/PCL; 70/30 wt.% blend were selected for in vivo evaluation in a rabbit model. Endoscopic observations revealed tissue features that were qualitatively consistent with the mechanical patterns predicted by the numerical simulations, although no direct causal relationship can be established from the available observations. These findings support the ability of the proposed framework to represent the principal aspects of stent–tissue interaction. The proposed computational framework provides a practical tool for the rational design and mechanical assessment of biodegradable airway stents and may facilitate the future development of customised airway prostheses.

Pulmonic stenosis (PS) is one of the most common congenital cardiac diseases in dogs. Although echocardiography and computed tomographic angiography (CTA) provide valuable diagnostic and anatomical information, the hemodynamic consequences of PS remain incompletely characterized. This study describes patient-specific pulmonary artery hemodynamics in dogs with and without PS using computational fluid dynamics (CFD). Contrast-enhanced CTA and echocardiographic data from five dogs with PS and five control dogs without PS were used to reconstruct three-dimensional pulmonary artery geometries and generate patient-specific CFD models. Pressure drop (Δp), blood flow velocity, mean wall shear stress (WSS), time-averaged WSS (TAWSS), oscillatory shear index (OSI), relative residence time (RRT), and pulmonary artery resistance were quantified and compared between groups. Dogs with PS exhibited markedly increased transvalvular pressure gradients, peak flow velocities, and pulmonary artery resistance, together with high-velocity jets and localized post-stenotic recirculation that were absent in control dogs. Mean WSS and TAWSS tended to be higher in the PS group, whereas OSI values were similar between groups. In contrast, RRT was significantly lower (p = 0.032) in dogs with PS. These findings demonstrate that patient-specific CFD enables detailed characterization of pulmonary artery hemodynamics in canine PS, providing information that complements conventional imaging. Although its clinical utility in veterinary medicine has yet to be fully established, CFD can provide valuable insight into flow behavior and disease pathophysiology; however, its ability to yield precise, clinically applicable quantitative values remains limited. This approach shows promise for future applications in the clinical evaluation of PS and other cardiovascular diseases, although further studies are warranted to determine its clinical relevance in veterinary medicine.

This work focuses on the development of a patient-specific transient CFD-FSI numerical model combined with the Time-Averaged Entropy Generation Rate (TAEGR) to predict hemodynamic parameters in the thoracic aorta, including the Oscillatory Shear Index (OSI) and the Time-Averaged Wall Shear Stress (TAWSS). While arterial blood flow can be modeled assuming either rigid or elastic arterial walls, the effect of wall compliance on these parameters, particularly on TAEGR, remains insufficiently characterized. Moreover, the interpretation of established indicators is not unique, as regions of vascular relevance may correspond to either high or low values of OSI and TAWSS. The proposed approach aims to identify symmetry and asymmetry in shear stress and entropy generation within the arterial wall, which are closely associated with the development of atherosclerotic plaque. Four aortas from clinical patients were analyzed using the proposed numerical framework to investigate blood flow behavior. The results revealed regions with high values of the hemodynamic parameters (OSI > 0.15, TAWSS >= 2 Pa, and TAEGR >= 20 W/m(3)K) predominantly located in the vicinity of the upper arterial branches. These regions, referred to as critical zones, are considered prone to the development of cardiovascular diseases, particularly atherosclerosis. The proposed numerical model provides a reliable qualitative framework for assessing symmetry and asymmetry in aortic blood flow patterns under different surgical conditions.

Tracheal stenosis significantly alters airway geometry, modifying flow acceleration, jet formation, and secondary recirculation patterns that strongly influence inhaled particle transport. When airway patency is restored using tracheal stents, additional geometric features are introduced that may further affect local flow structures and deposition mechanisms. In this work, we present a systematic parametric computational investigation of aerosol transport in stenosed and stented tracheas, focusing on the role of geometric severity and configuration together with patient-specific inspiratory flow conditions.Idealized upper airway models were constructed incorporating central and eccentric stenoses (right, left, and posterior) with area-reduction ratios of 30%, 50%, and 70%. In addition, Dumon tubular and Y-shaped stents with wall thicknesses of 1mm and 1.5mm were evaluated. Airflow and particle transport (1, 5, 10, and 15μm) were simulated using computational fluid dynamics coupled with a Lagrangian discrete phase approach.Results demonstrate that stenosis severity and eccentricity strongly govern particle fate through geometry-driven transport mechanisms. Increasing area reduction enhances jet-like acceleration and impaction upstream of the constriction, leading to dominant proximal deposition for larger particles. Eccentric configurations further promote asymmetric flow structures and localized deposition patterns. Stent implantation modifies these dynamics by reducing extreme flow acceleration but introduces new recirculation zones that influence particle retention, particularly for particles larger than 1μm. Additional controlled simulations performed using exchanged patient-specific inspiratory waveforms demonstrated that proximal deposition patterns are also strongly influenced by inlet-flow conditions, particularly for larger particles dominated by inertia-driven impaction. Under matched flow conditions, stenosed and stented geometries exhibited substantially more similar proximal deposition behaviour, while local and downstream regional deposition patterns remained sensitive to airway morphologyOverall, the findings highlight that deposition efficiency is governed by the coupled interaction between airway geometry and patient-specific inspiratory dynamics. While inspiratory flow conditions strongly influence proximal deposition, especially for larger particles, stenosis severity, eccentricity, and stent configuration continue to modulate local flow organization and regional particle transport. This parametric framework provides mechanistic insight into the coupled geometry-flow transport behaviour and supports more geometry-informed strategies for inhaled drug delivery in patients with tracheal pathology.

Endotracheal prosthesis placement is employed as a therapeutic intervention for tracheal lesions in cases where conventional surgical approaches are not feasible. The learning curve for endotracheal stent placement can vary depending on the type of stent, the training environment, and the clinician’s prior experience; however, it is generally considered moderately complex. Inadequate practice can have serious consequences, as the procedure involves a critical area such as the airway. The main risks and complications associated with inadequate technique or improper execution can include stent migration, formation of granulation tissue or hyperplasia, tracheal or pulmonary infection, obstruction or fracture of the stent, hemorrhage and tracheal perforation, among others. The purpose of the present study is to summarize important information and evaluate the role of different material features in the 3D printing manufacturing of an appropriate tracheobronchial medical device, which should be as appropriate as possible to facilitate placement during surgical practice. A complex stent design was fabricated using three different biodegradable materials, polycaprolactone (PCL), polydioxanone (PDO), and polymer blend of polylactic acid/polycaprolactone (PLA/PCL), through additive manufacturing, specifically fused filament fabrication (FFF)3D printing. Parameter optimization of the 3D printing process was required for each material to achieve an adequate geometric quality of the stent. Experimental analyses were conducted to characterize the mechanical properties of the printed stents. Flexural strength and radial compression resistance were evaluated, with particular emphasis on radial force due to its clinical relevance in preventing collapse after implantation in the trachea. The results provide valuable insights into how material selection could influence device behavior during placement to support surgical requirements.

Background and Objective: In this work, the analysis of the importance of hemodynamic updates on a mechanobiological model of atheroma plaque formation is proposed. Methods: For that, we use an idealized and axisymmetric model of carotid artery. In addition, the behavior of endothelial cells depending on hemodynamical changes is analyzed too. A total of three computational simulations are carried out and their results are compared: an uncoupled model and two models that consider the opposite behavior of endothelial cells caused by hemodynamic changes. The model considers transient blood flow using the Navier-Stokes equation. Plasma flow across the endothelium is determined with Darcy's law and the Kedem-Katchalsky equations, considering the three-pore model, which is also employed for the flow of substances across the endothelium. The behavior of the considered substances in the arterial wall is modeled with convection-diffusion-reaction equations, and the arterial wall is modeled as a hyperelastic Yeoh's material. Results: Significant variations are noted in both the morphology and stenosis ratio of the plaques when comparing the uncoupled model to the two models incorporating updates for geometry and hemodynamic stimuli. Besides, the phenomenon of double-stenosis is naturally reproduced in the models that consider both geometric and hemodynamical changes due to plaque growth, whereas it cannot be predicted in the uncoupled model. Conclusions: The findings indicate that integrating the plaque growth model with geometric and hemodynamic settings is essential in determining the ultimate shape and dimensions of the carotid plaque.

The placement of endotracheal prostheses is a procedure used to treat tracheal lesions when no other surgical options are available. Unfortunately, this technique remains controversial. Both silicon and metallic stents are used with unpredictable success rates, as they have advantages but also disadvantages. Typical side effects include restenosis due to epithelial hyperplasia, obstruction and granuloma formation. Repeat interventions are often required. Biodegradable stents are promising in the field of cardiovascular biomechanics but are not yet approved for use in the respiratory system. The aim of the present study is to summarize important information and to evaluate the role of different geometrical features for the fabrication of a new tracheo-bronchial prosthesis prototype, which should be biodegradable, adaptable to the patient’s lesion and producible by 3D printing. A parametric design and subsequent computational analysis using the finite element method is carried out. Two different stent designs are parameterized and analyzed. The biodegradable material chosen for simulations is polylactic acid. Experimental tests are conducted for assessing its mechanical properties. The role of the key design parameters on the radial force of the biodegradable prosthesis is investigated. The computational results allow us to elucidate the role of the pitch angle, the wire thickness and the number of cells or units, among other parameters, on the radial force. This work may be useful for the design of ad hoc airway stents according to the patient and type of lesion.

In this chapter, we present a numerical simulation of the aerosol particle inhalation, deposition, and transport in healthy and stented human upper airways. In particular, the aim of this chapter is oriented toward the comparison between healthy and stented subjects. The healthy tracheobronchial model is based on the Weibel asymmetric airways tree that includes the oral cavity and ends at the third generation. In this model, we have inserted the Dumon silicone prosthesis: a tracheal and two bronchial (left and right) prostheses. The numerical computations include light, normal, and heavy breathing conditions (15, 30, and 60 L/min, respectively) and different particle sizes (1, 5, and 10 μm). The obtained results indicate an important redistribution of the particle within the stented airways in comparison to the healthy case. In the stented model, the particles tend to deposit in the proximal regions of the prostheses, i.e., the trachea and the two main bronchi independently of the breathing conditions and of the particle size, even the situation is particularly enhanced at high flow rate. The amount of aerosol, which should theoretically reach the lungs, is hence reduced. Additionally, local hotspots are highlighted in these sites and may have negative secondary effects in the regions near the stent, which have been already damaged or inflamed due to the presence of the prosthesis. This chapter attempts to contribute to the understanding of the particle kinematics in the human airways and it is aimed to improve drug aerosol therapies studying the deposition and transport in stented airways. For patients that underwent airways surgery, this chapter may give information about the deposition efficiency yet helping to target specific regions of the lungs.

Animals have been widely utilized as surrogate models for humans in exposure testing, infectious disease experiments, and immunology studies. However, respiratory diseases affect both humans and animals. These disorders can spontaneously affect wild and domestic animals, impacting their quality and quantity of life. The origin of such responses can primarily be traced back to the pathogens deposited in the respiratory tract. There is a lack of understanding of the transport and deposition of respirable particulate matter (bio-aerosols or viruses) in either wild or domestic animals. Moreover, local dosimetry is more relevant than the total or regionally averaged doses in assessing exposure risks or therapeutic outcomes. An accurate prediction of the total and local dosimetry is the crucial first step to quantifying the dose-response relationship, which in turn necessitates detailed knowledge of animals’ respiratory tract and flow/aerosol dynamics within it. In this review, we examined the nasal anatomy and physiology (i.e., structure-function relationship) of different animals, including the dog, rat, rabbit, deer, rhombus monkey, cat, and other domestic and wild animals. Special attention was paid to the similarities and differences in the vestibular, respiratory, and olfactory regions among different species. The ventilation airflow and behaviors of inhaled aerosols were described as pertinent to the animals’ mechanisms for ventilation modulation and olfaction enhancement. In particular, sniffing, a breathing maneuver that animals often practice enhancing olfaction, was examined in detail in different animals. Animal models used in COVID-19 research were discussed. The advances and challenges of using numerical modeling in place of animal studies were discussed. The application of this technique in animals is relevant for bidirectional improvements in animal and human health.

En este trabajo se analiza la frecuencia de actualización de la geometría y principales variables hemodinámicas que conllevan el desarrollo de placa de ateroma en una geometría en dos dimensiones de arteria carótida. Dicho análisis se realiza sobre dos modelos con distintas hipótesis para la consideración de la reparación endotelial.

Salbutamol is a bronchodilatator commonly used for the treatment of feline inflammatory lower airway disease, including asthma or acute bronchospasm. As in humans, a pressurized metered dose inhaler (pMDI) is used in conjunction with a spacer and a spherical mask to facilitate salbutamol administration. However, efficacy of inhalation therapy is influenced by different factors including the non-cooperative character of cats. In this study, the goal was to use computational fluid dynamics (CFD) to analyze the impact of breathing patterns and salbutamol particle size on overall drug transport and deposition using a specific spherical mask and spacer designed for cats. A model incorporating three-dimensional cat airway geometry, a commercially available spherical mask, and a 10 cm spacer, was used for CFD analysis. Two peak inspiratory flows were tested: 30 mL/s and 126 mL/s. Simulations were performed with 30s breathing different inspiratory and expiratory times, respiratory frequencies and peaks. Droplet spray transport and deposition were simulated with different particle sizes typical of the drug delivery therapies (1, 5, 10, and 15 μm). The percentage of particle deposition into the device and upper airways decreased with increasing particle diameter during both flows imposed in this cat model. During increased mean ventilatory rate (MVR) conditions, most of the salbutamol was lost in the upper airways. And during decreased MVR conditions, most of the particles remained in suspension (still in hold-up) between the mask and the carina, indicating the need for more than 30 s to be transported. In both flows the percentage of particles traveling to the lung was low at 1.5%–2.3%. In conclusion, in contrast to what has been described in the human literature, the results from this feline model suggest that the percentage of particles deposited on the upper airway decreases with increasing particle diameter.

Intoduction:In veterinary medicine, airway management of cats under general anesthesia is performed with an endotracheal tube (ETT) or supraglottic airway device (SGAD). This study aims to describe the use of computational fluid dynamics (CFD) to assess the velocities, pressures, and resistances of cats with ETT or SGAD.Methods:A geometrical reconstruction model of the device, trachea, and lobar bronchi was carried out from computed tomography (CT) scans that include the head, neck, and thorax. Twenty CT scans of cats under general anesthesia using ETT (n = 10) and SGAD (n = 10) were modeled and analyzed. An inspiratory flow of 2.4 L/min was imposed in each model and velocity (m/s), general and regional pressures (cmH2O) were computed. General resistance (cmH2O/L/min) was calculated using differential pressure differences between the device inlet and lobar bronchi. Additionally, regional resistances were calculated at the device's connection with the breathing circuit (region A), at the glottis area for the SGAD, and the area of the ETT exit (bevel) (region B) and the device itself (region C).Results:Recirculatory flow and high velocities were found at the ETT's bevel and at the glottis level in the SGAD group. The pressure gradient (Δp) was more enhanced in the ETT cases compared with the SGAD cases, where the pressure change was drastic. In region A, the Δp was higher in the ETT group, while in regions B and C, it was higher in the SGAD group. The general resistance was not statistically significant between groups (p = 0.48). Higher resistances were found at the region A (p = <0.001) in the ETT group. In contrast, the resistance was higher in the SGAD cases at the region B (p = 0.001).Discussion:Overall, the provided CT-based CFD analysis demonstrated regional changes in airway pressure and resistance between ETT and SGAD during anesthetic flow conditions. Correct selection of the airway device size is recommended to avoid upper airway obstruction or changes in flow parameters.

The blood–brain barrier is a unique physiological structure acting as a filter for every molecule reaching the brain through the blood. For this reason, an effective pharmacologic treatment supplied to a patient by systemic circulation should first be capable of crossing the barrier. Standard cell cultures (or those based on microfluidic devices) and animal models have been used to study the human blood–brain barrier. Unfortunately, these tools have not yet reached a state of maturity because of the complexity of this physiological process aggravated by a high heterogeneity that is not easily recapitulated experimentally. In fact, the extensive research that has been performed and the preclinical trials carried out provided sometimes contradictory results, and the functionality of the barrier function is still not fully understood. In this study, we have combined tissue clarification, advanced microscopy and image analysis to develop a one-dimensional computational model of the microvasculature hemodynamics inside the mouse brain. This model can provide information about the flow regime, the pressure field and the wall shear stress among other fluid dynamics variables inside the barrier. Although it is a simplified model of the cerebral microvasculature, it allows a first insight on into the blood–brain barrier hemodynamics and offers several additional possibilities to systematically study the barrier microcirculatory processes.

The management of complex airway disorders is challenging, as the airway stent placement usually results in several complications. Tissue reaction to the foreign body, poor mechanical properties and inadequate fit of the stent in the airway are some of the reported problems. For this reason, the design of customized biomedical devices to improve the accuracy of the clinical results has recently gained interest. The aim of the present study is to introduce a parametric tool for the design of a new tracheo-bronchial stent that could be capable of improving some of the performances of the commercial devices. The proposed methodology is based on the computer aided design software and on the finite element modeling. The computational results are validated by a parallel experimental work that includes the production of selected stent configurations using the 3D printing technology and their compressive test.

Surgical treatment of coronary bifurcation in presence of two lesions is problematic due to postclinical complications. In recent years, fractional flow reserve has emerged as a valuable tool for assessing the functional severity of coronary stenosis in clinical practice. Numerical studies have facilitated prediction by idealized patient-specific biomechanical models. However, overall bifurcation hemodynamics in presence of stenotic lesions still needs to be better understood, to improve clinical intervention and reduce associated risks. In this chapter, we study the influence of serial stenotic coronary lesions on coronary blood flow, using a parametric model. Computational fluid dynamics simulations were carried out to characterize hemodynamic changes and fractional flow reserve according to various stenosis configurations and degrees of severity.

Good diagnosis of severity is essential for treatment of coronary stenosis. Several biomechanical reduced-order (0D) models have been developed to predict the true severity (fractional flow reserve: FFRTrue) of left main (LM) stenosis with downstream lesions. These models intend to assist the interventional cardiologist in pondering the need for a revascularization procedure, so as to avoid treating nonsignificant lesions and consequently reducing unnecessary risks. Although these studies report promising results for prediction of FFRTrue, they do not simultaneously consider (1) complex LM coronary stenosis configurations with two downstream lesions or (2) the influence of collateral circulation. We therefore developed a new 0D model to predict the true severity of LM stenosis, taking account of both of these factors. In vitro validation was performed to assess the accuracy and performance of the novel model. The model successfully clarified the influence of concomitant stenoses and collateral circulation on FFR amplitude in LM stenosis.