Biomedical subjects

Michael J Oldham

Publications and source records attributed to Michael J Oldham.

9 recordsLinked to original sources

PubMed2006

Interaction of epithelium with mesenchyme affects global features of lung architecture: a computer model of development.

Lung airway morphogenesis is simulated in a simplified diffusing environment that simulates the mesenchyme to explore the role of morphogens in airway architecture development. Simple rules govern local branching morphogenesis. Morphogen gradients are modeled by four pairs of sources and their diffusion through the mesenchyme. Sensitivity to lobar architecture and mesenchymal morphogen are explored. Even if the model accurately represents observed patterns of local development, it could not produce realistic global patterns of lung architecture if interaction with its environment was not taken into account, implying that reciprocal interaction between airway growth and morphogens in the mesenchyme plays a critical role in producing realistic global features of lung architecture.

Bronchi↗

PubMed2006

Tracheobronchial particle dose considerations for in vitro toxicology studies.

The purpose of this paper is to present a method for estimating particle doses that may be used to reconcile particle deposition doses used in in vitro toxicology studies with in vivo exposure levels. The focus is on the tracheobronchial (TB) tree of heavily exposed individuals. A review of the factors that influence inhaled particle deposition doses in environmental exposures leads to the identification of cases in which greater than average TB tree doses are received. Exercising individuals and those with chronic obstructive pulmonary disease not only inhale increased volumes of air but they also may have uneven ventilation that leads to greater than average particle deposition doses per unit of TB tree surface area. In addition, deposition hot spots, as occur at airway bifurcations, will greatly increase the particle exposures of target cells in the TB tree. Three particle exposure scenarios are proposed, and the average and local doses to the TB epithelium are calculated. When various factors that enhance particle doses (enhancement factors, or EFs) in vivo are considered, substantial particle doses may be justified for in vitro tissue culture studies that use TB target cells, such as epithelial cell cultures. The use of such EFs is intended to improve in vitro dosing with particles. Although the exposure of cells in vitro cannot fully replicate the complexity of in vivo exposures, it is possible to calculate toxicologically relevant doses that may define adverse health effects in potentially sensitive human populations. Local groups of TB cells in high-dose individuals are predicted to receive particle doses that are 3000-25,000 times higher than the doses averaged over the entire TB region.

Bronchi↗

PubMed2006

Experimental and numerical smoke carcinogen deposition in a multi-generation human replica tracheobronchial model.

A better understanding of submicron particle deposition in the respiratory tract is needed to study the health effects caused by carcinogenic particles. Recent studies indicate that random diffusion is not sufficient to describe the motion of these particles in complex geometries, rendering conventional models inaccurate. A solid replica of excised human lung segments was used to create digital and hollow models of the tracheobronchial region to investigate deposition of mainstream (MS) and sidestream (SS) cigarette smoke particles. Particle sizes for the carcinogen Benzo(a)pyrene (BaP) in SS smoke, and total particulate matter (UVPM) in SS and MS smoke were measured and used to compare the simulation to experimental data. Excellent agreement was found between predicted and measured results. Random diffusion was not found to be significant for submicron particles indicating that particles were instead transported to the airway wall by convective diffusion. BaP in SS smoke was an average 0.3 mum compared to 0.36 mum for UVPM in SS smoke. The trends in both experimental and numerical results indicated that the BaP in SS smoke deposits at a slightly higher efficiency than the UVPM, indicating that carcinogen-specific deposition, rather than total particulate matter should be considered when investigating health effects.

Benzopyrenes↗

PubMed2006

Aerosol dosimetry considerations.

The concept of dose is fundamental to the discipline of toxicology. For inhaled particles, dose considerations include the sequential processes of inhalation, particle deposition, and particle clearance. Several important parameters modify each of these processes, including environmental, anatomic, and physiologic factors. When such factors are considered, it is possible to identify subpopulations and individuals who are likely to receive particle doses that greatly exceed those for the average population. Higher than average doses can be expected for people who are young, have certain acute or chronic lung diseases, are engaged in exercise, or are exposed in close proximity to sources of air pollutants. Although considerable research has improved the understanding of inhaled particle doses, much is still to be learned before high-risk groups and individuals can be protected properly.

Aerosols↗

PubMed2006

Calculated deposition in growing tracheobronchial airways: effect of growth-rate assumptions.

Most current deterministic computer dosimetry models use idealized dichotomous symmetrical infant, child, and adolescent tracheobronchial geometries for dosimetry predictions. These tracheobronchial geometries were derived from either the morphometric measurements of J. D. Mortensen and colleagues or those of R. F. Phalen and colleagues. The airway growth curves used to create these geometries are typically means from all airways within a single generation in the tracheobronchial tree. This idealized approach implies that the growth rate of all airways in the same generation is identical (symmetric growth, SG), which is unlikely. In this study, existing morphometric measurements of airway dimensions were used to determine growth equations for airway length, diameter, branch angle, and inclination to gravity as a function of body height for each airway in the first four tracheobronchial generations. Tracheobronchial geometries (asymmetrical growth, AG) were created from these growth curves for the first 4 tracheobronchial generations representing a 4- and 11-yr-old child and an adult. Particle deposition predictions for steady inspiratory flow using 0.1- to 20-microm diameter monodisperse particles in these AG geometries were compared with predictions using the SG geometries using the uniform growth rate approach. Each airway in the first four generations had a unique airway length and diameter growth rate. Airway branch angle and inclination to gravity did not change as a function of body height. The unique airway growth rates resulted in significant differences in predicted deposition efficiency between the AG and SG geometry. Use of AG geometry may provide improved estimates of regional particle deposition in infants, children, and adolescents.

Adult↗

PubMed2006

Mutual enhancements of CFD modeling and experimental data: a case study of 1-mum particle deposition in a branching airway model.

In order to better understand aerosol dynamics and deposition in the complex flow field of the respiratory tract, both in vitro experiments and numerical modeling techniques have widely been employed. Computational fluid dynamics (CFD) modeling offers the flexibility of easily modifying system parameters such as flow rates, particle sizes, system geometry, and heterogeneous outlet conditions. However, a number of numerical errors and artifacts can lead to nonphysical CFD results. Experimental methods offer the advantage of physical realism; however, parameter variation is often difficult. The objective of this study is to illustrate the use of CFD to enhance the understanding of experimental results. In parallel, the selected experimental results have been used to partially validate the CFD predictions. A specific case study has been considered focusing on 1-mum particle depositions in a physiologically realistic bifurcation (PRB) model of respiratory generations 3-5. Previous experiments in this system report a deposition rate of approximately 0.01%. An in-depth CFD analysis has been employed to evaluate two cases of the empirical model. The first case consists of only the PRB double bifurcation geometry. The second case includes a portion of the experimental particle delivery system, which may influence the entering velocity and particle profiles. To assess the influence of upstream transition and turbulence, each of the two cases considered has been evaluated using laminar and low Reynolds number k-omega approximations. Results indicate that both upstream flow effects and turbulent or transitional flow play a significant role in determining the deposition of 1-mum particles in the model considered. Simulating upstream flow effects and laminar flow was required to match the empirically reported deposition fraction and provided a two orders of magnitude improvement over initial CFD estimates. This study highlights the need to consider the effects of experimental particle generation systems on velocity and particle profiles entering respiratory models. Future work is necessary to investigate the mechanisms responsible for the experimentally observed local deposition patterns.

Aerosols↗

PubMed2006

Challenges in validating CFD-derived inhaled aerosol deposition predictions.

Computational fluid dynamic (CFD) techniques have provided unprecedented opportunity for investigating inhaled particle deposition in realistic human airway geometries. Several recent articles describing local aerosol deposition predictions based upon "validated" CFD models have highlighted the challenges in validating local aerosol deposition predictions. These challenges include: (1) defining what is meant by validation; (2) defining appropriate experimental data for validation; and (3) determining when the agreement is not fortuitous. The term validation has numerous meanings, depending on the field and context in which it is used. For example, in computer programming it means the code executes as intended, to the experimentalist it means predicted results agree with matched experimental measurements, and to the risk assessor it implies that predictions using new parameters can be trusted. Based on the current literature it is not clear that a consensus exists for what constitutes a validated CFD model. It is also not clear what types of experimental data are needed or how closely the CFD input values and experimental conditions should be matched (similar or identical airway geometries, entrance airflow, or aerosol profiles) to validate CFD derived predictions. Due to the complexity of CFD computer codes and the multiplicity of deposition mechanisms, it is possible that total aerosol deposition may be accurately predicted and the resulting local particle deposition patterns are incorrect, or vice versa. Specific examples and suggestions for several challenges to experimentalists and modelers are presented.

Aerosols↗

PubMed2004

Performance of a portable whole-body mouse exposure system.

A mobile whole-body exposure system was developed for exposing mice to concentrated ambient particulate matter smaller than 2.5 microm in mass median aerodynamic diameter (MMAD). Each 20-L exposure cage was designed to hold 9 mice within individual compartments. This allowed for transport and subsequent exposure. Airflow mixing and the potential for stagnant areas within the compartments were modeled using computational fluid dynamic modeling (CFD). CFD analysis showed no stagnant areas and good mixing throughout the exposure cage. The actual performance of the exposure system was determined for 0.5 to 2.0 microm diameter aerosols by measuring (1) uniformity of aerosol distribution and (2) particle deposition in the tracheobronchial and pulmonary regions of mice exposed in the system. A 0.6-microm MMAD (GSD=2.0) cigarette smoke aerosol was used to experimentally measure the uniformity of aerosol distribution to the nine individual compartments. The average data from three runs showed no statistically significant difference among individual compartments. Particle deposition efficiency in adult male BALB/c mice was measured after exposure (30 min) in the system using monodisperse fluorescent polystyrene latex particles (0.5, 1, and 2 microm aerodynamic diameter). The measured deposition efficiency in this mobile exposure system for the combined tracheobronchial and pulmonary regions of the adult male BALBc mice was 21% for 0.5 microm, 11% for 1.0 microm, and 6.5% for 2.0 microm particles. These deposition efficiencies are similar to those reported for mice exposed in a nose-only exposure system, which indicates that particle losses to animal fur and exposure system surfaces were acceptable.

Aerosols↗

PubMed2002

Dosimetry implications of upper tracheobronchial airway anatomy in two mouse varieties.

Strain- and variety-related differences in responses of mice have been reported for a variety of inhaled particulate and gaseous materials. It is important to understand the potential contributions to such responses of differences in delivered doses to the respiratory tract as well as differences in biochemical processes. Deposition doses of inhaled particles are influenced by several factors, including airway anatomy, ventilation, and particle characteristics. Tracheobronchial airway morphometry for airway generations 1-6 of the BALB/c mouse was generated using replica lung casts prepared in situ. Measurements were performed on two groups: control and ovalbumin-sensitized male BALB/c mice. These measurements were compared with previously published airway morphometry of male B6C3F(1) mice. Sensitization did not significantly change measured airway dimensions in the BALB/c mouse. However, the two mouse varieties had significant differences in airway anatomy. The differences found in airway anatomy between mouse varieties correlated with differences in body length and chest circumference. Particle deposition predictions for both varieties of mice were performed for unit density spherical particles from 0.1 to 10 microm in diameter at two ventilation rates using a published aerosol dosimetry computer code. Particle deposition in the proximal tracheobronchial tree ranged up to 3 times greater for the BALB/c mouse for a 2 microm particle diameter and high ventilation rate. These differences in predicted particle deposition suggest that observed strain and variety differences in response to inhaled particulate matter may be in part due to differences in delivered doses to the respiratory tract.

Aerosols↗