Detailed Analysis of Fiber Motion in Human Nasal Airways

Information on the fiber particle transport and deposition in human nasal airways is of great importance in inhalation toxicology study. Due to the complex interactions between the inhaled aerosol particles and human respiratory airways, the particles’ toxicity varies with their chemical composition, size, and shape. In the earlier computational study of fiber particle motion in human nasal cavities, overall deposition efficiency curves were evaluated and compared with the available experimental data. The majority of investigations were on micron-scale fiber particles, and the observed deposition fraction is strongly affected by fiber inertial impaction and the geometry of the cavity. The fiber characterization by its equivalent spheres is still not entirely fully understood. Limited existing evidence indicated that, when benchmarked by the impaction parameter, spherical particles tend to have a higher deposition fraction than that of the elongated fiber particles in the nasal cavity. More data is needed to elaborate on these observations and reveal the underlying physics. A more profound understanding of fiber transport in human airways may be obtained by comparing the fibrous particle deposition to that of the spherical particles. In this study, simulations of transport and deposition of elongated particles in a realistic human nasal cavity model for a steady laminar airflow rate were performed. FLUENT 19.2 was used to solve the airflow conditions. The elongated ellipsoidal particle transport and deposition were simulated using the coupled translational and rotational equations of motion. The hydrodynamic drag and torque, shear-induced lift, and gravitational force were included in the analysis. One-way coupling was assumed, and an in-house User Defined Function (UDF) was developed and was implemented into the ANSYS-FLUENT code for analyzing the fiber transport and deposition. The airflow field, the particle deposition efficiency, particle deposition pattern, and single-particle trajectories of fiber and sphere were analyzed and presented. The simulation results were compared with available experimental data and simulation results in the literature.

Comparison of Two Models to Estimate Deposition of Fungi and Bacteria in the Human Respiratory Tract

Understanding the deposition of bioaerosols in the respiratory system may help determine the risk of disease; however, measuring deposition fraction in-situ is difficult. Computational models provide estimates of particle deposition fraction for given breathing and particle parameters; however, these models traditionally have not focused on bioaerosols. We calculated deposition fractions in an average-sized adult with a new bioaerosol-specific lung deposition model, BAIL, and with two multiple-path models for three different breathing scenarios: “default” (subject sitting upright and breathing nasally), “light exercise”, and “mouth breathing”. Within each scenario, breathing parameters and bioaerosol characteristics were kept the same across all three models. BAIL generally calculated a higher deposition fraction in the extrathoracic (ET) region and a lower deposition fraction in the alveolar region than the multiple-path models. Deposition fractions in the tracheobronchial region were similar among the three models; total deposition fraction patterns tended to be driven by the ET deposition fraction, with BAIL resulting in higher deposition in some scenarios. The difference between deposition fractions calculated by BAIL and other models depended on particle size, with BAIL generally indicating lower total deposition for bacteria-sized bioaerosols. We conclude that BAIL predicts somewhat lower deposition and, potentially, reduced risk of illness from smaller bioaerosols that cause illness due to deposition in the alveolar region. On the other hand, it suggests higher deposition in the ET region, especially for light exercise and mouth-breathing scenarios. Additional comparisons between the models for other breathing scenarios, people’s age, and different bioaerosol particles will help improve our understanding of bioaerosol deposition.

A Precise Scale-Up Method to Predict Particle Delivered Dose in a Human Respiratory System Using Rat Deposition Data: An In Silico Study

As surrogates to human beings, rats are used occasionally to study the therapeutic impact of inhaled pulmonary drug particles in microscale. To speculate human responses from rat studies, scale-up factors are widely used to extrapolate particle lung deposition from rat to human. However, available scale-up methods are highly simplified and not accurate, because they directly use the human-to-rat ratios of body weights (RBW) or lung surface areas (RSA) as the scale-up factor. To find a precise scale-up strategy, an experimentally validated Computational Fluid-Particle Dynamics (CFPD) was employed to simulate the transport and deposition of microparticles in both human and rate respiratory systems, which encompasses the pulmonary routes from mouth/nose to airways up to Generation 17 (G17) for human and G23 for the rat. Microparticles with the same range of Stk/Fr were injected into both models with the airflow at resting conditions. Numerical results indicate that particles (with the size ranging from 1 to 13 μm for humans and 0.6 to 6 μm for rat) have similar deposition pattern (DP) and deposition fraction (DF) in both models, which are resulted from both inertial impaction and gravitational sedimentation effects. A novel correlation is proposed to predict DFs in both human and rat respiratory systems as a function of the ratio of Stokes number to Froude number (Stk/Fr). Using the correlation as the novel scale-up tool, inter-species extrapolations can be precisely done on predicting particle depositions in human respiratory systems based on the deposition data in rats obtained from animal studies.

Comparative numerical simulation of inhaled particle dispersion in upper human airway to analyse intersubject differences

This study predicted the total and regional deposition of particles in realistic upper human airways and demonstrated the effects of intersubject variations in deposition fraction. Two airway models were studied under flow rates ranging from 0.45 to 2.4 m3/h and particle aerodynamic diameters from 1 to 10 μm. The total deposition predictions were validated using in vivo and in vitro experimental data. The intricate airway structures generated heterogeneities of airflow distributions and corresponding particle dispersions and depositions in the models. Nevertheless, with modified inertial parameters, the total deposition fraction curves of the two human upper airway models, as functions of flow rates, converged to a single function. However, regional particle deposition fractions differed significantly among the two models. The surface pressure and wall-shear stress distribution were investigated to assess the relationship of surface pressure and wall-shear stress with hotspot locations in upper airways of both models. For one subject (model A), the central nasal passage regions were found to be sites of higher deposition over the range of particle sizes and flow rates targeted in this study. For the other subject (model B), higher deposition was mostly observed in the vestibule region, caused due to particle inertia as the airway consisted of curvatures. The accelerated flow regions acted as a natural filter to high inertial particles. The results indicated that both total and regional depositions exhibited significant intersubject differences.

Numerical investigation of the lower airway exposure to indoor particulate contaminants

Inhalation exposure to indoor particulate contaminants contributes as one of the leading threats to public health. Most existing airway morphometry models are either theoretical or semi-empirical; these are developed for predicting deposition fractions for an averaged general population subgroup. It is difficult to customize a fast and accurate prediction on individual basis. This study aims to analyse the regional particle deposition along an anatomically correct airway model, which is developed from a healthy volunteer’s computer tomography images. Computational fluid dynamics simulation results show that the majority of particles are deposited in the bronchi. Accumulation particles (0.1–2.0 μm) have the smallest deposition fraction in the lower airways. An increase in the aerodynamic diameter >2.0 μm of the particles elevated the deposition fraction. These findings inspire future investigations into control methods that minimize the negative health impact of indoor emissions.

Deposition of Ellipsoidal Fibers in Nasal Cavity: Influence of Non-Creeping Flow Conditions

In this study, deposition fraction of ellipsoidal particles in a 3D-Model of the nasal cavity (right airway) of a 24-year-old healthy woman was simulated for laminar and turbulent inhalation flow rates. The geometry used included the main nasal cavity from the nostril to the beginning of nasopharynx and was constructed in the Ansys-ICEM software from a CT scan image. The numerical simulations of governing equations were obtained using the Ansys-Fluent software. The mean airflow was assumed to be incompressible and steady. For turbulence modeling, the Realizable k-ε model was employed and the Lagrangian trajectory analysis method was used for particle tracking. For evaluating the ellipsoidal particle motions, several user-defined functions (UDFs) were developed and linked to the discrete phase model of the Ansys-Fluent code. The developed UDFs solve for the coupled translational and rotational equations of motion for ellipsoidal fibers and also accounts for the stochastic modeling of turbulence velocity fluctuations. The hydrodynamic forces and torques were calculated based on the non-creeping formulations for various ellipsoidal fibers. Laminar flow condition was assumed for breathing rate of 5.0 lit/min for the rest or light physical activities and turbulent flow condition was assumed for airflow rate of 20 lit/min for high physical activities. To investigate the dispersion and deposition of particles in the model of the human nasal cavity, various fibers with a semi-minor axis of 1, 3, 5 and 10 μm and various aspect ratios were considered. Using the non-creeping flow formulation for hydrodynamic forces and torques, the simulation results showed slight differences in the total deposition fraction of ellipsoidal fibers compared with the corresponding creeping flow model. Small fibers deposit roughly uniformly in the nasal cavity with no hotspot region. For the large inertial fibers, however, the nasal valve is a hot spot region, where the deposition rate reaches to its peak.

Simulation of Airway Deposition of an Aerosol Drug in COPD Patients

Medical aerosols are key elements of current chronic obstructive pulmonary disease (COPD) therapy. Therapeutic effects are conditioned by the delivery of the right amount of medication to the right place within the airways, that is, to the drug receptors. Deposition of the inhaled drugs is sensitive to the breathing pattern of the patients which is also connected with the patient’s disease severity. The objective of this work was to measure the realistic inhalation profiles of mild, moderate, and severe COPD patients, simulate the deposition patterns of Symbicort® Turbuhaler® dry powder drug and compare them to similar patterns of healthy control subjects. For this purpose, a stochastic airway deposition model has been applied. Our results revealed that the amount of drug depositing within the lungs correlated with the degree of disease severity. While drug deposition fraction in the lungs of mild COPD patients compared with that of healthy subjects (28% versus 31%), lung deposition fraction characteristic of severe COPD patients was lower by a factor of almost two (about 17%). Deposition fraction of moderate COPD patients was in-between (23%). This implies that for the same inhaler dosage severe COPD patients receive a significantly lower lung dose, although, they would need more.