Abstract  In five normal subjects the total deposition for nose- and mouth-breathing of monodisperse airborne di-2-ethylhexyl sebacate droplets in the diameter range from 0·1 to 3·2 μm was studied for a variety of breathing patterns without respiratory pauses. The calculation of deposition was based upon measurements of the particle number concentration and the respiratory flow rate at the mouth or the nose. For all subjects and all particle sizes deposition fell with increasing gas volume of the respiratory tract. However, when inhalations were initiated at the subjects' normal functional residual capacities no individual differences in deposition for mouth-breathing were found in contrast to nose-breathing deposition. For a constant flow rate the deposition rose with increasing tidal volume, whereas for a constant tidal volume the deposition fell with increasing breathing frequency indicating that time-dependent deposition mechanisms are more effective than velocity-dependent mechanisms. Whenever the mean residence time of the particles in the respiratory tract was short deposition for mouth-breathing was found to be almost independent of particle size in the diameter range below 1 μm revealing the significance of mixing. The deposition values obtained were lower than those usually accepted. The reasons for this are discussed.

Abstract  Data were collected from the literature on respiratory variables and cor-related aginast body weight on the assumption of log-log relationships (allometry) with the use of computer regression analysis. Statistically validated power law formulas, with correlation coefficients of 0. 99-0. 90, are presented for lung weight, VC[long dash]vital capacity, TLC[long dash]total lung capacity, FRC[long dash]functional residual capacity, VT-tidal volume, VD, O2, E. f[long dash]number of breaths/min, Cl[long dash]pulmonary compliance, DLCO-Diffusing capacity of the lung for CO, DLO2-Diffusing capacity of the lung for 02, total respiratory flow resistance, work per breath, and several nonrespiratory parameters. The study deals principally with the rat-human size range, but the prediction formulas probably cover mice to steer and possibly all mammals. Predicted and observed values are compared for the rat, cat, dog, and man; good agreement is demonstrated. Size-independent dimensionless and dimensional respiratory invariants or design parameters may be obtained by forming simple and complex quotients from the individual power laws that have net residual mass exponents (dependency on body weight) approaching zero.

Abstract  A previously developed deposition model is used to determine the total and regional deposition of inhaled aerosols in a population of human lungs by taking into account variability in airway dimensions. The results for particle sizes ranging from 0.1 micron to 8 micron aerodynamic diameter agree favorably with experimental data, thus suggesting that observed intersubject deposition variability is caused primarily by difference in airway dimensions.

Abstract  Regional deposition of inhaled particles was studied experimentally for 9 health subjects breathing the same aerosol under the same breathing conditions in order to evaluate intersubject variability of regional deposition. A great intersubject variability of extrathoracic, tracheobronchial and alveolar deposition was found. The highest one was observed for particle deposition in the extrathoracic airways. This biological variability of regional deposition has to be taken into account for considerations of health related aspects of aerosol inhalation.

Abstract  The respiratory anatomic dead space has been measured by the single breath nitrogen washout method of Fowler in 73 normal subjects ranging from 4 to 42 years of age. The volume of the anatomic dead space correlated closely with height (Vd (ml) = 7.585 x Ht (cm)2.363 x 10-4·ɣ = .917), but also with body weight, surface area, and functional residual capacity. When compared on the basis of any of these parameters there was no significant difference between the anatomic dead space values for males and females. Comparisons with available data for newborn infants suggest that the value of the anatomic dead space has a relatively constant relation to height from birth to adulthood. Dead space appears to increase more rapidly than weight, surface area, and functional residual capacity during, at least, the early period of somatic growth.

Abstract  We recorded maximum expiratory flow-volume curves in 3046 healthy persons, blacks and whites, age 7 and over — a representative population of lifetime nonsmokers except for some black adults males, who were healthy smokers or ex-smokers. We computed regression equations for lung function measurements (FVC, FEV1.0, FEV1.0/FVC, PEF, MEF, 50% and MEF 25%) as a function of age, height and weight terms for eight subgroups (by sex and race, and for children or adults). Objective statistical criteria were used to select the optimal equations. Simple linear regressions on age and height are inaccurate, in particular for young adults and for the elderly. Weight affects most function measurements: lung function first increases with weight (‘muscularity effect’)_ and decreases with further increases in weight (‘obesity effect’). The regression equations allow more accurate prediction of normal lung function. In addition, the lower 95% confidence limits are closer to the predicted values and are valid regardless of height, weight and age within each subgroup.

Abstract  The alveolo-bronchial and the lymphatic pathways are most important in pulmonary clearance of relatively insoluble particles. We were interested in studying the effect of the lung burden on the size of the fraction cleared via the lymphatic system. TiO2 particles, representing the “inert and insoluble” class of particulate matter, were used in rats utilizing both intratracheal instillation and inhalation exposures. After a single exposure about 40–45% of the deposited particles are cleared from the lung in 25 days and about 0.7% are found in the hilar lymph nodes at low exposures. At high exposures lung clearance decreases, in some experiments to zero values, and the lymph node content increases to ∼4%. At low exposures both exposure techniques result in similar clearance values; however, the lymphatic node content rises with increased lung burden faster after intratracheal instillation. The possible mechanisms involved are discussed.

Abstract  Dr. Yu's project addressed several important issues regarding improved quantification of dose from known concentrations of atmospheric particulate matter. By focusing first on a specific category of automotive-derived particles, diesel exhaust particulate, Dr. Yu was able to characterize those aerosol properties (such as the mass medican aerodynamic diameter and size distribution) that influence regional deposition. After formulating a mathematical deposition model, Dr. Yu calculated and compared the deposition of inhaled diesel exhaust particulate in laboratory animals and in humans of different ages.

Abstract  Models of the lung airways of a rat were developed from complete measurements of the tracheobronchial airways. A silicone rubber cast of the tracheobronchial airways of a rat lung was prepared and all individual airway segments down to and including the terminal bronchioles were measured to obtain the segment diameters, lengths, branching angles and angles of inclination to gravity. Models of the rat tracheobronchial airways were constructed based on the original measurements and the subsequent analysis. Some mathematical assumptions about acinar anatomy distal to terminal bronchioles were made to extend the models to include pulmonary regions. Emphasis was placed on the "Typical Path Lung Model" which used one typical pathway to represent either a whole lung or a lobe of the lung. The models are simple and can be applied in calculation of physiologic variables or particle deposition during inhalation in various lobes of the lung.

Abstract  Because the retractive forces due to surface tension decrease with increasing radius of curvature, there should be a greater contribution to lung recoil attributable to the stress-bearing role of elastic elements in the lung parenchyma of species with larger alveoli. To examine alterations in lung structure that may relate to this stress-bearing role, the lungs of mice, hamsters, rats, rabbits, rhesus monkeys, baboons, and humans were preserved by vascular perfusion of fixative. The number of alveoli per lung, alveolar radius of curvature, surface area, and volume were measured by serial section reconstruction. Electron-microscopic determinations were made of the volume fraction and thickness of the epithelium, interstitium, and endothelium and of the connective tissue fibers of the alveolar septa and the portions of alveolar septa that form the alveolar ducts. The thickness of the alveolar septal interstitium increased linearly with the increase in radius of curvature of alveoli. The increase in interstitial thickness in lungs with larger alveoli was paralleled by large increases in the volume of collagen and elastin fibers present in this space. Comparable changes in the thickness of connective tissue fibers in alveolar duct walls were also found. This study demonstrates species-related changes in the structure of alveolar septa and in lung collagen and elastin fibers that are consistent with connective tissue fibers having a greater stress-bearing role in both the alveolar septa and alveolar ducts of species with larger alveoli.

Abstract  Morphometric procedures were used to determine the number of cells, cell volume, cell diameter, and surface areas of the airways in human and rat lungs. Nuclear sizes of epithelial cells from human bronchi were significantly larger than other lung cell nuclei. The average volume of human ciliated cell nuclei was 310 ± 30 Ám(3) and 167 ± 12 Ám(3) in bronchi and bronchioles, respectively. The smaller nuclei of human bronchioles were comparable to those of alveolar cells. In the pseudostratified epithelium of human bronchi, basal cells had a large surface area in contact with the basement membrane (51.3 ± 4.6 Ám(2) per cell) when compared with ciliated (1.1 ± 0.1 Ám(2)), goblet (7.6 ± 1.2 Ám(2)), or other secretory cells (12.0 ± 2.1 Ám(2)). In the first four airway generations distal to the trachea, basal cells account for 30% of the cells in human airway epithelium and 2% of the cells in rat airway epithelium. Total airway surface area from trachea to bronchioles was 2,471 ± 320 and 27.2 ± 1.7 cm(2) in human and rat lungs, respectively. These direct measurements of airway surface area are less than half of the estimates based on current lung models. The total number of airway epithelial cells were 10.5 x 10(9) for human and 0.05 X 10(9) for rat lungs. For both species, there were 18 times more alveolar cells than bronchial epithelial cells.

Abstract  The growth of single dry salt aerosol particles during respiration in human airways is calculated with equations for the mass and heat transport to the particle surface (Ferron, J. Aerosol Sci. 8, 251, 1977) and with axial profiles for the temperature (T) and relative humidity (RH) of the air in the human respiratory tract as derived in a previous study (Ferron et al., J. Aerosol Sci. 19, 343, 1988). The calculations are performed for single dry NaCl, CoCl2.6H2O and ZnSO4.7H2O particles representing salts with large, medium and small increases of particle size in nearly saturated air. The growth of a salt particle is a function of the initial dry particle size, the molecular weight of the salt, its density, and its dissociation constant. It is affected by the profile of the RH of the air in the upper human respiratory tract. Pure salt particles with initial sizes below 1 μm reach their final size during inhalation, whereas particles with initial sizes larger than 7 μm change their size by less than 20% during inhalation. The growth of a salt particle with initial size below 3 μm is influenced by the inhalation airflow. The influence of the reduced transport of water vapor and heat in the lower bronchial tree simulated by a correction equation has hardly any effect on the growth of salt particles. The deposition of salt particles in the human respiratory tract is calculated with a model published before (Ferron et al., J. Aerosol Sci. 16, 133, 1985a). The model is adapted to calculate the deposition of particles with a changing particle diameter. The calculated total lung deposition is enhanced for particles with initial diameter larger than 0.2 μm and reduced for particles with initial diameter less than 0.15 μm with respect to the deposition of non-growing particles. The largest increase in total deposition is found for 1 μm-sized particles. As a first approximation the values for the regional deposition of growing and non-growing particles differ by the same factor as the total deposition is changed. Particles with an initial dry size between 1 and 7 μm have a deposition probability larger than 70% in the bronchial and pulmonary region. A recommendation to estimate the deposition of hygroscopic aerosol particles is derived.

Abstract  Airborne monodisperse particles in the size range 2.5–7.5 μm dia., labelled with 99mTc, were systematically administered to mouth breathing subjects under different but predetermined breathing patterns ranging from 0.5–2.01, tidal volume and 10–25 breaths/min. The subjects were all healthy, non-smoking males. Measurements were made of both total and regional deposition. The results show the increasing significance of pulmonary deposition as the particle size decreases and consequently the importance of accurate data in this range for the purposes of radiological protection. Both total and regional deposition are a function of the impaction parameter (D2F) suggesting that inertial impaction is the main mechanism of deposition under the conditions studied. The work supports the predicted values of deposition given in the lung model of the International Commission on Radiological Protection. Subsidiary experiments showed the value of faecal sampling in establishing the accuracy of total deposition estimates and in elucidating full regional deposition.

Abstract  A new growth equation for pure water and solution droplets with radii≳1µm has been developed which features discrete vapor and temperature fields at the surface of growing droplets. The discrete fields are created by the condensation and thermal accommodation coefficients in order to maintain steady state in the vapor and heat transfers. The newly derived equation is compared with previous theories, and their differences and ranges of applicability are clarified. It is shown that the newly derived equation includes some of the previous equations as special cases. The new equation is numerically evaluated and graphically examined for the case of pure water droplets. The results show a spreading tendency in size distribution of formed droplets at the start of their growth. The present theory and equations may also be applied to the evaporation of a droplet and the growth of an ice particle where the shape can he assumed to be spherical.

Abstract  In 4 subjects with normal lung function total deposition of monodisperse, hydrophobic, uncharged silver particles in the 0.005 to 0.08 μm size range was investigated for a variety of breathing patterns during steady state mouth- and nose breathing. The evaluation of deposition was based upon measurements of mean particle number concentration in inspired and expired air by means of a condensation nucleus counter. Owing to the diffusional particle transport, total deposition increases with decreasing particle size and increasing mean residence time of the aerosol in the lungs. With decreasing particle size the time dependence becomes less and the effect of tidal volume more significant. A semi-empirical formula is derived which fits the experimental data.

Abstract  A quantitative study of postnatal lung growth has been made and shows that the number of alveoli increases over tenfold between birth and adult life. This increase occurs mainly in the first eight years. After this age, increase in lung volume takes place by increase in linear dimensions of existing alveoli. The mean number of generations of airways increases from 21 to 23, from 3 months to 8 years of age. This increase takes place in the most distal respiratory airways. There is a linear relationship between the surface area of the air-tissue interface and the body surface area during the period of growth. It is suggested that information of this type may well be useful in assessing such conditions as pulmonary hypoplasia, respiratory syndrome of the newborn, and the lung in prematurity.

Abstract  Accurate extrapolation of animal toxicity data for human health risk assessment requires determination of the effective dose to the target tissue and the sensitivity of the target tissue to that dose. The methodology for deriving reference doses [the U.S. Environmental Protection Agency's (EPA) benchmark values for gauging systemic toxicity] for oral exposures has not included dosimetry modeling. Dosimetry data facilitate evaluation of concentration-response data with respect to the dose-response relationships used in quantitative risk assessment. Extension of this methodology to derivation of inhalation reference doses (RfDi) should account for the dynamics of the respiratory system as the portal of entry. Predictive physiologically based modeling of the inhalation of reactive gases has recently been demonstrated (Overton and Miller 1988). Models that describe the deposition of hygroscopic particles and account for chemical factors that affect clearance mechanisms and gas uptake are under development. This paper presents a method for calculating a dosimetric adjustment factor based on the values for the initial deposited dose of insoluble particles in an animal species and in humans. The ratio of these two values serves as a scaling factor that can be applied in the R f D methodology to account for the dosimetric differences in the inhaled deposited dose. This application for insoluble particles illustrates the feasibility of interspecies dosimetry calculations for extrapolating the toxicological results of inhaled agents to human exposure conditions for more accurate risk estimation.

Abstract  A thorough analysis of aerosol particle deposition in the human lung requires the knowledge of the distribution of inspired air at respiration. In this paper, a mathematical model of ventilation distribution has been developed using a five-lobe airway model. The model accounts for the nonlinear effects of compliance and resistance on airway dynamics. Ventilation distributions were determined under different gravitational force conditions. A larger gravity leads to a greater nonuniformity of ventilation between the upper and lower lobes of the lung. Ventilation distributions in different lobes of the lung at various inspiratory flow rates were also calculated. At slow inspiratory flow rates, ventilation was found to be nonuniform with more air entering the lower lobes. As the flow rate increased, this nonuniformity became smaller. The calculated results compare favorably with existing experimental data. When a different gas was inspired instead of air, a preferential distribution of ventilation to the upper lobes was found if the density of the inspired gas was greater than that of the air.

Abstract  Lung diseases caused by the inhalation of various particulate pollutants have often been reported to occur at specific sites in the lung with some diseases preferentially occurring in one of the lobes. Models for the dosimetry of particulate matter in the lung, therefore, need to be developed at a level of resolution that allows for the study of lobar- and airway-specific patterns of deposition. Using an approach best described as a combination of multiple- and single-path approaches to modeling lung geometry, we calculated deposition of particulate matter (PM) ranging from ultrafine to coarse particles in each airway down to the level of the lobar bronchi. Further down the airway tree, we calculated deposition averaged over an airway generation in each lung lobe. We compared our results for regional and lobar deposition with various experimental data as well as with results from other models. The calculated results compared reasonably well with experimental data. Significant variations in deposition were observed among the lobar bronchi as well as among the five lobes. The differences among the lobes were accentuated as one examined generation-specific deposition. Deposition per unit surface area of each lobar bronchus was considerably elevated relative to that calculated for the whole lung. The relative distribution of aerosol deposited per unit surface area among the various lobar bronchi was altered by breathing condition and aerosol size. Our observations suggest that a multiple-path model that incorporates the heterogeneous structure of airways in the lung is likely to reduce uncertainties in PM health risk assessments.

Abstract  This model calculates the deposition and clearance of monodisperse and polydisperse aerosols in the respiratory tract of rats, human adults and children (deposition only) for particles ranging from ultrafine (0.01 microns) to coarse (20 microns) sizes. The models are based upon single-path and multiple-path methods for tracking air flow and calculating aerosol deposition in the lung. The single-path method calculates deposition in a typical path per airway generation, while the multiple-path method calculates particle deposition in all airways of the lung and provides lobar-specific and airway-specific information. Within each airway, deposition is calculated using theoretically derived efficiencies for deposition by diffusion, sedimentation and impaction within the airway or airway bifurcation. Filtration of aerosols by the head (nose and mouth) is determined using empirical efficiency functions.

Abstract  The sites of uptake and retention of inhalants within the respiratory tract influence which tissues are susceptible to damage. Physical and chemical properties of inhalants, including size, water:air and oil:water partition coefficients, and reactivity or susceptibility to metabolism are the major factors that affect deposition and retention. The high metabolic capacity of the cells of the olfactory tissue and bronchiolar Clara cells contributes to their susceptibility to damage from both inhaled and bloodborne toxicants. The major enzymes that metabolize pesticides and many other potential toxicants are the cytochrome P450 and flavin-containing monooxygenases and the carboxylesterases.