Comprehensive experimental and numerical validation of Lattice Boltzmann fluid flow and particle simulations in a child respiratory tract.

The numerical simulation of inhaled aerosols in medical research starts to play a crucial role in understanding local deposition within the respiratory tract, a feat often unattainable experimentally. Research on children is particularly challenging due to the limited availability of in vivo data and the inherent morphological intricacies. CFD solvers based on Finite Volume Methods (FVM) have been widely employed to solve the flow field in such studies. Recently, Lattice Boltzmann Methods (LBM), a mesoscopic approach, have gained prominence, especially for their scalability on High-Performance Computers. This study endeavours to compare the effectiveness of LBM and FVM in simulating particulate flows within a child's respiratory tract, supporting research related to particle deposition and medication delivery using LBM. Considering a 5-year-old child's airway model at a steady inspiratory flow, the results are compared with in vitro experiments. Notably, both LBM and FVM exhibit favourable agreement with experimental data for the mean velocity field and the turbulence intensity. For particle deposition, both numerical methods yield comparable results, aligning well with in vitro experiments across a particle size range of 0.1-20 µm. Discrepancies are identified in the upper airways and trachea, indicating a lower deposition fraction than in the experiment. Nonetheless, both LBM and FVM offer invaluable insights into particle behaviour for different sizes, which are not easily achievable experimentally. In terms of practical implications, the findings of this study hold significance for respiratory medicine and drug delivery systems - potential health impacts, targeted drug delivery strategies or optimisation of respiratory therapies.

Liposomal form of erlotinib for local inhalation administration and efficiency of its transport to the lungs.

This contribution is focused on the preparation of a liposomal drug delivery system of erlotinib resisting the nebulization process that could be used for local treatment of non-small-cell lung cancer. Liposomes with different compositions were formulated to reveal their influence on the encapsulation efficiency of erlotinib. An encapsulation efficiency higher than 98 % was achieved for all vesicles containing phosphatidic acid (d ≈ 100 nm, ζ = - 43 mV) even in the presence of polyethylene glycol (d ≈ 150 nm, ζ = - 17 mV) which decreased this value in all other formulas. The three most promising formulations were nebulized by two air-jet and two vibrating mesh nebulizers, and the aerosol deposition in lungs was calculated by tools of computational fluid and particle mechanics. According to the numerical simulations and measurements of liposomal stability, air-jet nebulizers generated larger portion of the aerosol able to penetrate deeper into the lungs, but the delivery is likely to be more efficient when the formulation is administered by Aerogen Solo vibrating mesh nebulizer because of a higher portion of intact vesicles after the nebulization. The leakage of encapsulated drug from liposomes nebulized by this nebulizer was lower than 2 % for all chosen vesicles.

The effect of oral and nasal breathing on the deposition of inhaled particles in upper and tracheobronchial airways.

The inhalation route has a substantial influence on the fate of inhaled particles. An outbreak of infectious diseases such as COVID-19, influenza or tuberculosis depends on the site of deposition of the inhaled pathogens. But the knowledge of respiratory deposition is important also for occupational safety or targeted delivery of inhaled pharmaceuticals. Simulations utilizing computational fluid dynamics are becoming available to a wide spectrum of users and they can undoubtedly bring detailed predictions of regional deposition of particles. However, if those simulations are to be trusted, they must be validated by experimental data. This article presents simulations and experiments performed on a geometry of airways which is available to other users and thus those results can be used for intercomparison between different research groups. In particular, three hypotheses were tested. First: Oral breathing and combined breathing are equivalent in terms of particle deposition in TB airways, as the pressure resistance of the nasal cavity is so high that the inhaled aerosol flows mostly through the oral cavity in both cases. Second: The influence of the inhalation route (nasal, oral or combined) on the regional distribution of the deposited particles downstream of the trachea is negligible. Third: Simulations can accurately and credibly predict deposition hotspots. The maximum spatial resolution of predicted deposition achievable by current methods was searched for. The simulations were performed using large-eddy simulation, the flow measurements were done by laser Doppler anemometry and the deposition has been measured by positron emission tomography in a realistic replica of human airways. Limitations and sources of uncertainties of the experimental methods were identified. The results confirmed that the high-pressure resistance of the nasal cavity leads to practically identical velocity profiles, even above the glottis for the mouth, and combined mouth and nose breathing. The distribution of deposited particles downstream of the trachea was not influenced by the inhalation route. The carina of the first bifurcation was not among the main deposition hotspots regardless of the inhalation route or flow rate. On the other hand, the deposition hotspots were identified by both CFD and experiments in the second bifurcation in both lungs, and to a lesser extent also in both the third bifurcations in the left lung.

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.

Multicomponent aerosol particle deposition in a realistic cast of the human upper respiratory tract.

Inhalation of aerosols generated by electronic cigarettes leads to deposition of multiple chemical compounds in the human airways. In this work, an experimental method to determine regional deposition of multicomponent aerosols in an in vitro segmented, realistic human lung geometry was developed and applied to two aerosols, i.e. a monodisperse glycerol aerosol and a multicomponent aerosol. The method comprised the following steps: (1) lung cast model preparation, (2) aerosol generation and exposure, (3) extraction of deposited mass, (4) chemical quantification and (5) data processing. The method showed good agreement with literature data for the deposition efficiency when using a monodisperse glycerol aerosol, with a mass median aerodynamic diameter (MMAD) of 2.3 µm and a constant flow rate of 15 L/min. The highest deposition surface density rate was observed in the bifurcation segments, indicating inertial impaction deposition. The experimental method was also applied to the deposition of a nebulized multicomponent aerosol with a MMAD of 0.50 µm and a constant flow rate of 15 L/min. The deposited amounts of glycerol, propylene glycol and nicotine were quantified. The three analyzed compounds showed similar deposition patterns and fractions as for the monodisperse glycerol aerosol, indicating that the compounds most likely deposited as parts of the same droplets. The developed method can be used to determine regional deposition for multicomponent aerosols, provided that the compounds are of low volatility. The generated data can be used to validate aerosol deposition simulations and to gain insight in deposition of electronic cigarette aerosols in human airways.

Numerical investigation of inspiratory airflow in a realistic model of the human tracheobronchial airways and a comparison with experimental results.

In this article, the results of numerical simulations using computational fluid dynamics (CFD) and a comparison with experiments performed with phase Doppler anemometry are presented. The simulations and experiments were conducted in a realistic model of the human airways, which comprised the throat, trachea and tracheobronchial tree up to the fourth generation. A full inspiration/expiration breathing cycle was used with tidal volumes 0.5 and 1 L, which correspond to a sedentary regime and deep breath, respectively. The length of the entire breathing cycle was 4 s, with inspiration and expiration each lasting 2 s. As a boundary condition for the CFD simulations, experimentally obtained flow rate distribution in 10 terminal airways was used with zero pressure resistance at the throat inlet. CCM+ CFD code (Adapco) was used with an SST k-ω low-Reynolds Number RANS model. The total number of polyhedral control volumes was 2.6 million with a time step of 0.001 s. Comparisons were made at several points in eight cross sections selected according to experiments in the trachea and the left and right bronchi. The results agree well with experiments involving the oscillation (temporal relocation) of flow structures in the majority of the cross sections and individual local positions. Velocity field simulation in several cross sections shows a very unstable flow field, which originates in the tracheal laryngeal jet and propagates far downstream with the formation of separation zones in both left and right airways. The RANS simulation agrees with the experiments in almost all the cross sections and shows unstable local flow structures and a quantitatively acceptable solution for the time-averaged flow field.

Development of a realistic human airway model.

Numerous models of human lungs with various levels of idealization have been reported in the literature; consequently, results acquired using these models are difficult to compare to in vivo measurements. We have developed a set of model components based on realistic geometries, which permits the analysis of the effects of subsequent model simplification. A realistic digital upper airway geometry except for the lack of an oral cavity has been created which proved suitable both for computational fluid dynamics (CFD) simulations and for the fabrication of physical models. Subsequently, an oral cavity was added to the tracheobronchial geometry. The airway geometry including the oral cavity was adjusted to enable fabrication of a semi-realistic model. Five physical models were created based on these three digital geometries. Two optically transparent models, one with and one without the oral cavity, were constructed for flow velocity measurements, two realistic segmented models, one with and one without the oral cavity, were constructed for particle deposition measurements, and a semi-realistic model with glass cylindrical airways was developed for optical measurements of flow velocity and in situ particle size measurements. One-dimensional phase doppler anemometry measurements were made and compared to the CFD calculations for this model and good agreement was obtained.