Predictions of inter- and intra-lobar deposition patterns of inhaled particles in a five-lobe lung model.

OBJECTIVE: To develop a stochastic five-lobe lung model and to compute particle deposition fractions in the five lobes, considering anatomical as well as ventilatory asymmetry. MATERIALS AND METHODS: The stochastic five-lobe lung model was derived from an existing stochastic model for the whole lung, which implicitly contains information on the lobar airway structure. Differences in lobar ventilation and sequential filling of individual lobes were simulated by a stochastic lobar ventilation model. Deposition fractions of inhaled unit density particles in the five lobes were calculated by an updated version of the Monte Carlo deposition code Inhalation, Deposition, and Exhalation of Aerosols in the Lung (IDEAL). RESULTS: Simulations for defined exposure and breathing conditions revealed that the two lower lobes receive higher deposition and the two upper lobes lower deposition, compared to the average deposition for the whole lung. The resulting inter-lobar distribution of deposition fractions indicated that the non-uniform lung morphometry is the dominating effect, while non-uniform ventilation only slightly enhances the lobar differences. The relation between average lobe-specific deposition fractions and corresponding average values for the whole lung allowed the calculation of lobe-specific deposition weighting factors. DISCUSSION: Comparison with limited deposition measurements for upper vs. lower (U/L) and left vs. right (L/R) lobes revealed overall agreement between experimental and theoretical data. Calculations of the L/R deposition ratio for inhaled aerosol boli confirmed the hypothesis of Möller et al. that the right lung is less able to expand at the end of a breath because of the restrictive position of the liver.

Ultrafine urban particle measurements in Budapest and their airway deposition distribution calculation.

OBJECTIVES: The aim of this study was to provide particle number and mass deposition rates of submicron particles in the human airways as inputs for toxicology and other areas of aerosol science. METHODS: Scanning Mobility Particle Spectrometer was used to measure the number concentrations and size distributions of the ultrafine urban particles during summer and winter in Budapest. The Stochastic Lung Model (SLM) was applied to calculate number and mass deposition rates of the inhaled particles in different anatomical regions of the airways. RESULTS: Our calculations revealed that for the selected days in summer and winter with PM10 values below the health limit 4.7 and 18.4 billion particles deposited in the bronchial region of the lungs. The deposition in the acinar region of the lung was even higher, 8.3 billion particles for the summer day, and 33.8 billion particles for winter day. CONCLUSIONS: Our results clearly demonstrate that large daily numbers of urban UFPs are deposited in the respiratory tract, which may play a key role in the health effects of particulate matter (PM) inhalation. Present results, connecting the ambient exposure parameters with the local burden of the airway epithelium, can be useful inputs of in vitro cell culture experiments. By the combination of urban UFP monitoring and numerical modeling of particle deposition with toxicological studies, the health risks of urban aerosols could be better assessed. The use of UFP data in addition to PM10 and PM2.5 in the epidemiological studies would also be indicated.

The degree of inhomogeneity of the absorbed cell nucleus doses in the bronchial region of the human respiratory tract.

Inhalation of short-lived radon progeny is an important cause of lung cancer. To characterize the absorbed doses in the bronchial region of the airways due to inhaled radon progeny, mostly regional lung deposition models, like the Human Respiratory Tract Model (HRTM) of the International Commission on Radiological Protection, are used. However, in this model the site specificity of radiation burden in the airways due to deposition and fast airway clearance of radon progeny is not described. Therefore, in the present study, the Radact version of the stochastic lung model was used to quantify the cellular radiation dose distribution at airway generation level and to simulate the kinetics of the deposited radon progeny resulting from the moving mucus layer. All simulations were performed assuming an isotope ratio typical for an average dwelling, and breathing mode characteristic of a healthy adult sitting man. The study demonstrates that the cell nuclei receiving high doses are non-uniformly distributed within the bronchial airway generations. The results revealed that the maximum of the radiation burden is at the first few bronchial airway generations of the respiratory tract, where most of the lung carcinomas of former uranium miners were found. Based on the results of the present simulations, it can be stated that regional lung models may not be fully adequate to describe the radiation burden due to radon progeny. A more realistic and precise calculation of the absorbed doses from the decay of radon progeny to the lung requires deposition and clearance to be simulated by realistic models of airway generations.

Computer-aided generation and lung deposition modeling of nano-scale particle aggregates.

The study sets its main focus on the introduction of a random-walk-based model for the generation of variably shaped particle aggregates consisting of a predefined number of spherical components. With the help of a well-defined algorithm, the user is enabled to select between isodimensional, chain-like and platelet-like aggregates, for which related aerodynamic parameters (dynamic shape factors, volume-equivalent diameters, aerodynamic diameters) are determined automatically. The theoretical approach for random aggregate construction is directly connected with the previously developed stochastic particle transport and deposition model. Thereby, individually shaped aggregates may be provided for each random-walk scenario taking place in the almost realistic lung structure. Preliminary application of the aggregate generation model was carried out by assuming single components with a constant diameter of 1 nm and unit-density (1 g cm-3) and variably shaped aggregates consisting of 10, 100 and 1000 components. Inhalation of the aggregate-loaded aerosol into lungs of average size (FRC = 3300 mL) was supposed to take place under sitting, light-exercise and heavy-exercise conditions. Results obtained from deposition modeling clearly show that, independent of aggregate geometry, total deposition declines with increasing number of components included in the particulate construct, but experiences a continuous enhancement with rising inhalation flow rate. Among the predefined geometric categories, platelet-like aggregates are distinguished by lowest deposition and isodimensional clusters by highest. While isodimensional aggregates preferentially deposit in the extrathoracic and bronchial airways, chain-like and platelet-like aggregates exhibit a significantly increased tendency to hit the alveolar walls.

Comparison of airway deposition distributions of particles in healthy and diseased workers in an Egyptian industrial site.

The objective of this study is the prediction and comparison of airway deposition patterns of an industrial aerosol in healthy workers and workers suffering from silicosis. Mass concentrations and related size distributions of particulate matter were measured in the industrial area of Samalut in Minia, Egypt. A novel stochastic lung deposition model, simulating the symptoms of silicosis by chronic bronchial (Br) obstruction and emphysema in the acinar (Ac) region, was applied to compute mass deposition fractions, deposition density, deposition rate and deposition density rate distributions in healthy and diseased workers. In the case of healthy workers, both mass deposition fractions and deposition rates are highest in the first half of the Ac region of the lung, while the corresponding deposition density and deposition density rate distributions exhibit a maximum in the large Br airways. In the case of diseased lungs, bullous emphysema causes a large deposition peak in the region of the bronchioli respiratorii. Regional mass deposition fractions adopt maximum values in the extrathoracic region, except during mouth breathing for bullous emphysema, where Ac deposition can be the most prominent. In general, lung deposition is significantly higher in diseased than in healthy lungs. Indeed, workers suffering from silicosis receive significantly higher Ac doses than healthy workers exposed to the same aerosol. Thus, this illness may progress faster if a diseased worker remains in a strongly polluted area.

A stochastic model of carbon nanotube deposition in the airways and alveoli of the human respiratory tract.

CONTEXT: In the past two decades, possible exposure of workers to nanoparticles has excited the attention of occupational medicine, resulting in the conception of related risk assessments. Although most nanoparticles have been categorized as hazardous substances in the meantime, their behavior in the human respiratory tract still bears some enigmas, which require clarification. OBJECTIVES: The study pursues the goal to provide detailed theoretical lung deposition data of carbon nanotubes (CNT) with various diameters and lengths. Besides a quantification of total and regional deposition, also airway generation-specific deposition has been subjected to the modeling process. METHODS: Theoretical approach of CNT deposition in the human lungs has been conducted by assuming a stochastic structure of the bronchial network, within which particle transport takes place along randomly selected paths. Fluid-dynamic particle characteristics have been simulated by application of a rigid fiber model, which considers diverse forces and torques acting on the particles during their translocation within the inhaled air. Particle deposition in the entire lungs has been approximated by using the aerodynamic/thermodynamic diameter concept and related empirical deposition formulae. RESULTS: Theoretical deposition data reflect a significant dependence of CNT deposition on (a) the effective size of the particles and (b) the conditions, under which they are taken up into the respiratory tract. Extremely small CNT (∼1 nm) are primarily filtered in the extrathoracic airways, intermediately sized CNT (∼10 nm) exhibit a preference to deposit in the alveoli, and large CNT (∼100 nm) are marked by minimum deposition. CONCLUSION: Pulmonary deposition of CNT is subject to a partly remarkable variation. According to the model of this study, particles of intermediate size seem to bear highest potential to act as hazardous substances.

Effect of Oral Pathway on Charged Particles Deposition in Human Bronchial Airways.

BACKGROUND: In vitro studies to investigate the effect of charged particle deposition in the oral pathway of human adults have demonstrated substantial increases in deposition due to an induced charge effect. In the current study, charged particle deposition in the oral pathway was incorporated in the stochastic human airway generation model IDEAL (Inhalation, Deposition, and Exhalation of Aerosols in the Lung) to quantify their effect on bronchial airways deposition. METHODS: Calculation of increased oral deposition due to charged particles was performed by a modified version of IDEAL for oral pathway, whereas deposition in the bronchial airways was carried out by the already employed efficiency equation. Deposition calculations were performed for 3, 4.5, and 6 µm particles at flow rates of 15 and 30 L/min. RESULTS: The enhancement in deposition is found to be 40 times higher in oral pathway and 6 times higher in bronchial airways for 3 µm size particles carrying 2500 elementary charges. For particles larger than 3 µm, deposition by impaction dominates over deposition by particle charges, and hence higher deposition in oral pathway is observed primarily due to impaction. As a consequence of this increased oral deposition, bronchial airways deposition decreases. CONCLUSION: By controlling breathing, aerosol properties, and electrostatic charge, targeted deposition in the human airways can be improved. Hence, charged particles can therefore be utilized to give better control on regional drug delivery in the lungs or to filter out toxic constituents.

Theoretical models for the simulation of particle deposition and tracheobronchial clearance in lungs of patients with chronic bronchitis.

INTRODUCTION: Based upon theoretical models particle deposition and clearance in human respiratory systems affected by chronic bronchitis can be approximated reliably. As a consequence of those hypothetical results, optimal frame conditions (e.g., inhalation time and volume, particle properties) for inhalation therapies can be determined. METHODS: Simulation of particle deposition was conducted by modelling a partly or fully obstructed tracheobronchial architecture. Bronchitis-induced reductions of the airway calibres were computed by application of specific scaling factors. Three different scenarios of chronic bronchitis were modelled. Brownian motion, inertial impaction, interception, and gravitational settling were assumed as main deposition forces influencing inhaled particular mass. Tracheobronchial clearance was approximated by application of generation-specific mucus velocities as well as the consideration of a slow bronchial clearance phase, whose half-time varied between 5 and 20 days. RESULTS: Under different breathing conditions (i.e., sitting and light-work breathing) deposition of submicron and µm-sized particles is significantly enhanced within the bronchial lung region, but also alveolar deposition becomes partly enhanced. By changing the inhalation conditions target sites of therapeutic aerosols may be reached with rather high accuracy. Based on the data of this modified models, particle retention in lung airways of patients suffering from chronic bronchitis may be noticeably prolonged, with 24-hour retention values being increased by up to 50%. DISCUSSION AND CONCLUSIONS: As exhibited by the results, particle deposition behaviour in lungs affected by chronic bronchitis differs remarkably from that in healthy lungs. These theoretical finds are mostly supported by experimental data. Further, experimental and theoretical deposition results may be used for an estimation of the grade of disease. Tracheobronchial clearance reduces its efficiency with each progress of the disease which increases the probability of bacterial infections in the airways.

Theoretical models of carcinogenic particle deposition and clearance in children's lungs.

INTRODUCTION: Deposition and clearance of carcinogenic particles in the lungs of subjects belonging to four different age groups (infants, children, adolescents, and adults) were theoretically investigated. The study is thought to contribute to the improvement of our knowledge concerning the behaviour of inhaled particles in lungs that may be attributed to different stages of development. METHODS: Particle deposition and clearance were simulated by using a well established stochastic lung model, allowing the generation of nearly realistic scenarios. For the computation of particle deposition all main deposition forces were considered. Additionally, any influences on particle behaviour due to particle geometry were covered by using the aerodynamic diameter concept. Particle clearance was simulated by defining both a fast mucociliary clearance phase and a slow bronchial/alveolar clearance phase, the latter of which is based on previously published models and suggestions. RESULTS: As clearly provided by the modelling computations, lung deposition of particles with aerodynamic diameters ranging from 1 nm to 10 µm may significantly differ between the studied age groups. Whilst in infants and children most particles are accumulated in the extrathoracic region and in the upper bronchi, in adolescents and adults high percentages of inhaled particular substances may also reach the lower bronchi and alveoli. Although mucus velocities are significantly lower in young subjects compared to the older ones, fast clearance is more efficient in small lungs due to the shorter clearance paths that have to be passed. Slow clearance is commonly characterized by insignificant discrepancies between the age groups. CONCLUSIONS: From the study presented here it may be concluded that particle behaviour in infants' and children's lungs has to be regarded in a different light with respect to that in adolescents and adults. Although young subjects possess natural mechanisms of protecting their lungs from hazardous aerosols (e.g., expressed by breathing behaviour and lung size), they are much more sensitive to any particle exposure, since particle concentrations per lung tissue area may reach alarming values within a short period of inhalation.