Renate Winkler-Heil

Modeling intersubject variability of particle deposition in human lungs

Abstract The morphological variability in human lungs was simulated by 10 multiple-path lung models, generated on the basis of probability distributions and correlations of airway parameters provided by the stochastic lung model of Koblinger and Hofmann (Phys. Med. Biol. 30 (1985) 541). Total, regional and generation-per-generation deposition was computed for particle sizes in the range of 0.01– 10 μm under resting breathing conditions. Our calculations suggest that structural and volumetric differences of lung morphologies among different individuals are primarily responsible for the experimentally observed intersubject variability in total and regional deposition under controlled breathing conditions. Individual differences in deposition among single airways can be substantially larger than those in total and regional deposition. Furthermore, variations are most pronounced for small (0.01 μm ) and large (10 μm ) particles.

Effect of particle mass size distribution on the deposition of aerosols in the human respiratory system

Elemental mass size distributions were experimentally determined in atmospheric aerosols collected at four different locations in Budapest, Hungary, comprising a urban background site, two downtown sites and a road tunnel. Based on these distributions, deposition fractions for the various elements in the respiratory system were calculated for a healthy Caucasian adult male, female and 5-year-old child under sitting breathing conditions by a stochastic lung deposition model. The highest deposition values were observed in the extrathoracic region regardless of subjects age and gender, and chemical species and size distributions. Deposition in the tracheobronchial tree and acinar region was much smaller than that in the extrathoracic region. Variations in the deposition fractions due to differences in the size distributions were really significant only in the extrathoracic region. Surprisingly, the different size distributions yielded similar depositions in the thoracic region for a given gender as far as the shape of the deposition curve and the total amount are concerned. Regional deposition fractions were compared for the male, female and child, and for various size distributions (sampling location) and elements.

The effect of morphological variability on surface deposition densities of inhaled particles in human bronchial and acinar airways.

Deposition fractions in human airway generations were computed with a stochastic deposition model, which is based on a randomly, asymmetrically dividing lung morphology, applying Monte Carlo techniques. Corresponding uncorrelated surface deposition densities were obtained by dividing the average deposition fraction in a given generation by the average total surface area of that generation. In order to consider the statistical correlation between deposition probability and linear airway dimensions in each airway, correlated surface deposition densities were calculated by dividing the deposition fraction in a randomly selected bronchial or acinar airway by the surface area of that airway and by the total number of bronchial or acinar airways in that generation. Average surface deposition densities are relatively constant throughout bronchial airway generations, while average acinar surface deposition densities exhibit a distinct decrease with rising penetration into the acinar region. Due to the correlation between deposition fraction and surface area in a given airway generation, average correlated surface deposition densities are consistently higher than average uncorrelated densities, particularly in the acinar region, where differences can be as high as a few orders of magnitude. Already significant statistical fluctuations of the deposition fractions in individual airway generations are even exacerbated for surface deposition densities, with coefficients of variation about twice as high as for correlated deposition fractions.

Deposition of combustion aerosols in the human respiratory tract: Comparison of theoretical predictions with experimental data considering nonspherical shape

Total deposition of petrol and diesel combustion aerosols and environmental tobacco smoke (ETS) particles in the human respiratory tract for nasal breathing conditions was computed for 14 nonsmoking volunteers, considering the specific pulmonary function parameters of each volunteer and the specific size distribution for each inhalation experiment. Theoretical predictions were 34.6% for petrol smoke, 24.0% for diesel smoke, and 18.5% for ETS particles. Compared to the experimental results, predicted deposition values were consistently smaller than the measured data (41.4% for petrol smoke, 29.6% for diesel smoke, and 36.2% for ETS particles). The apparent discrepancy between experimental data on total deposition and modeling results may be reconciled by considering the nonspherical shape of the test aerosols by diameter-dependent dynamic shape factors to account for differences between mobility-equivalent and volume-equivalent or thermodynamic diameters. While the application of dynamic shape factors is able to explain the observed differences for petrol and diesel combustion particles, additional mechanisms may be required for ETS particle deposition, such as the size reduction upon inspiration by evaporation of volatile compounds and/or condensation-induced restructuring, and, possibly, electrical charge effects.

Lung dosimetry for inhaled radon progeny in smokers

Cigarette smoking may change the morphological and physiological parameters of the lung. Thus the primary objective of the present study was to investigate to what extent these smoke-induced changes can modify deposition, clearance and resulting doses of inhaled radon progeny relative to healthy non-smokers (NSs). Doses to sensitive bronchial target cells were computed for four categories of smokers: (1) Light, short-term (LST) smokers, (2) light, long-term (LLT) smokers, (3) heavy, short-term (HST) smokers and (4) heavy, long-term (HLT) smokers. Because of only small changes of morphological and physiological parameters, doses for the LST smokers hardly differed from those for NSs. For LLT and HST smokers, even a protective effect could be observed, caused by a thicker mucus layer and increased mucus velocities. Only in the case of HLT smokers were doses higher by about a factor of 2 than those for NSs, caused primarily by impaired mucociliary clearance, higher breathing frequency, reduced lung volume and airway obstructions. These higher doses suggest that the contribution of inhaled radon progeny to the risk of lung cancer in smokers may be higher than currently assumed on the basis of NS doses.

Calculation of hygroscopic particle deposition in the human lung.

Abstract Context: Inhaled hygroscopic aerosols will absorb water vapor from the warm and humid air of the human lung, thus growing in size and consequently changing their deposition properties. Objective: The objectives of the present study are to study the effect of a stochastic lung structure on individual particle growth and related deposition patterns and to predict local deposition patterns for different hygroscopic aerosols. Materials and methods: The hygroscopic particle growth model proposed by Ferron et al. has been implemented into the stochastic asymmetric lung deposition model IDEAL. Deposition patterns were calculated for sodium chloride (NaCl), cobalt chloride (CoCl2 · 6H2O), and zinc sulfate (ZnSO4 · 7H2O) aerosols, representing high, medium and low hygroscopic growth factors. Results: Hygroscopic growth decreases deposition of submicron particles compared to hydrophobic particles with equivalent diameters due to a less efficient diffusion mechanism, while the more efficient impaction and sedimentation mechanisms increase total deposition for micron-sized particles. Due to the variability and asymmetry of the human airway system, individual trajectories of inhaled particles are associated with individual growth factors, thereby enhancing the variability of the resulting deposition patterns. Discussion and conclusions: Comparisons of model predictions with several experimental data for ultrafine and micrometer-sized particles indicate good agreement, considering intersubject variations of morphometric parameters as well as differences between experimental conditions and modeling assumptions.

Modeling intersubject variability of bronchial doses for inhaled radon progeny.

The main sources of intersubject variations considered in the present study were: (1) size and structure of nasal and oral passages, affecting extrathoracic deposition and, in further consequence, the fraction of the inhaled activity reaching the bronchial region; (2) size and asymmetric branching of the human bronchial airway system, leading to variations of diameters, lengths, branching angles, etc.; (3) respiratory parameters, such as tidal volume, and breathing frequency; (4) mucociliary clearance rates; and (5) thickness of the bronchial epithelium and depth of target cells, related to airway diameters. For the calculation of deposition fractions, retained surface activities, and bronchial doses, parameter values were randomly selected from their corresponding probability density functions, derived from experimental data, by applying Monte Carlo methods. Bronchial doses, expressed in mGy WLM−1, were computed for specific mining conditions, i.e., for defined size distributions, unattached fractions, and physical activities. Resulting bronchial dose distributions could be approximated by lognormal distributions. Geometric standard deviations illustrating intersubject variations ranged from about 2 in the trachea to about 7 in peripheral bronchiolar airways. The major sources of the intersubject variability of bronchial doses for inhaled radon progeny are the asymmetry and variability of the linear airway dimensions, the filtering efficiency of the nasal passages, and the thickness of the bronchial epithelium, while fluctuations of the respiratory parameters and mucociliary clearance rates seem to compensate each other.

Radon lung dosimetry models

Two different modelling approaches are currently used to calculate short-lived radon progeny doses to the lungs: the semi-empirical compartment model proposed by the International Commission on Radiological Protection and deterministic and stochastic airway generation models. The stochastic generation model IDEAL-DOSE simulates lung morphometry, transport, deposition and clearance of inhaled radionuclides, and cellular dosimetry by Monte Carlo methods. Specific dosimetric issues addressed in this paper are: (1) distributions of bronchial doses among and within bronchial airway generations; (2) relative contributions of radon progeny directly deposited in a given airway generation and those passing through from downstream generations to the bronchial dose in that generation; (3) distribution of bronchial doses among the five lobes of the human lung; (4) inhomogeneity of surface activities and resulting doses within bronchial airway bifurcations; (5) comparison of bronchial doses between non-smokers and smokers; (6) relative contributions of sensitive target cells in bronchial epithelium to lung cancer induction and (7) intra- and intersubject variations of bronchial doses.

Comparison of modeling concepts for radon progeny lung dosimetry

Abstract The computation of cellular doses requires the development of four interrelated models: (i) morphometric models of the human airway system; (ii) models for radon progeny deposition in bronchial airways; (iii) models for particle clearance in bronchial airways; and (iv) dosimetric models for energy deposition in sensitive target cells in bronchial epithelium. This study focuses on the effects of different modeling concepts and mechanisms resulting to cellular doses for each of the above model categories rather than on parameter variations. For example, several morphometric lung models have been published which differ in terms of airway structure and lung volume, thereby affecting the particle deposition efficiencies. Likewise, different mechanisms of particle clearance in bronchial airways have been proposed, such as fast mucociliary clearance and a slow macrophage-mediated clearance. The present comparison of a variety of modeling concepts suggests that the choice of specific modeling assumptions is as important for dose calculations as the choice of proper parameter values. Since some of the models and mechanisms analysed in the present study differ from those employed in the recent ICRP model, dose estimates will consequently differ from ICRP predictions. Indeed, the dosimetry model presented here predicts a weighted effective dose of 7.6 (6.2) mSv/WLM for indoor exposure conditions, as compared to 14.5 mSv/WLM based on the ICRP model. Thus, considering the inherent uncertainties in modeling assumptions and epidemiological analysis, dosimetric estimates do not differ appreciably from the epidemiologically derived dose convention of about 4 mSv/WLM.

Composition, size distribution and lung deposition distribution of aerosols collected in the atmosphere of a speleotherapeutic cave situated below Budapest, Hungary

Abstract Elemental composition and mass size distribution of cave aerosols were determined by PIXE on seven-stage cascade impactor samples collected in two different sites of the Szemlőhegy-cave, a speleotherapeutic cave situated below Budapest, Hungary. In addition, individual particle analysis was also performed on about 450 aerosol particles. Significant differences were found between the two sampling sites and also in comparison with the external air in both the size distribution and in the composition of the aerosol. On the basis of the obtained data a stochastic lung deposition model was used to calculate total and regional deposition efficiencies of the different types of particles along the human respiratory system. One can conclude that the extrathoracic deposition is quite significant and its role increasing with increasing respiratory minute volume. The regional thoracic deposition is not very sensitive to the size distribution and it has a maximum around the 15–20th airway generations.