Grantee Research Project Results

2008 Progress Report: Project 5 -- Architecture Development and Particle Deposition

EPA Grant Number: R832414C005
Subproject: this is subproject number 005 , established and managed by the Center Director under grant R832414
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Center for the Study of Metals in the Environment
Center Director: Allen, Herbert E.
Title: Project 5 -- Architecture Development and Particle Deposition
Investigators: Wexler, Anthony S. , Schelegle, Ed
Current Investigators: Wexler, Anthony S. , Plopper, Charles
Institution: University of California - Davis
EPA Project Officer: Chung, Serena
Project Period: October 1, 2005 through September 30, 2010 (Extended to September 30, 2011)
Project Period Covered by this Report: October 1, 2007 through September 30,2008
RFA: Particulate Matter Research Centers (2004) RFA Text | Recipients Lists
Research Category: Human Health , Air

Objective:

Quantify lung architecture, pulmonary function and particle deposition pattern changes due to pollutant exposure during development.

Approach:

We will use both experimental and modeling approaches to reach the objectives. Rats will be exposed to ozone, particles, and particles with ozone during different stages of development. We will perform lung function tests and measure airway architecture on normal and exposed adults. Comparing normal and exposed architecture and function will elucidate the significant changes that are due to the pollutants. Particle deposition patterns will also be measured and predicted with mathematical models to understand how alterations in architecture might increase particle deposition or change its location.

Progress Summary:

Three current activities are highlighted below: (1) characterization of normal rat lung architecture, (2) lung architecture and function changes due to ozone exposure during development, and (3) development of a combustion particle generator for exposing animals to PM during development.

1. Characterization of normal rat lung architecture

We analyzed the airway architecture of six normal rats using an algorithm to characterize model airway architecture that we developed previously (Lee et al. 2008). On the whole, inter-subject variability was small both in generation- and diameter-based analysis. Variation of airway size with generation number (Figure 1) indicates that global features of airway architecture are similar between subjects. Variations of asymmetry, branching angle and rotation angle shows that more detailed features are similar between subjects (Figure 2). Furthermore, distribution functions of asymmetry and rotation angle were very similar between subjects (Figure 3). Overall, these patterns in airway architecture indicate that models based on only several rats can be representative if a sufficient number of airways are analyzed.

Current study also showed that the mean value and standard deviation of the geometric parameters are insufficient to characterize airway architecture in the lung. For example, we found that the twist angle, i.e., the angle between successive bifurcations, is far from normally distributed. Thus, the typical distribution of the values of airway geometry must be taken into account to quantitatively describe pulmonary architecture.

2. Lung architecture and function changes due to ozone exposure during development

To test the effects of ozone exposure during lung development period, Sprague-Dawley rat pups (20 pups for each group) were exposed to filtered air or to 0.2 or 0.5 ppm ozone 8hrs/night, 5days/week from 7 days to 28 days after birth. At 56 days (after 28 days recovery), lung mechanics were evaluated for half of them and half of them were casted to analyze lung architecture.

For lung architecture, diameter, length rotation angle, branching angle, asymmetry based on generation or airway diameter were calculated and fractal analysis were conducted. There were no significant difference between control and exposures in lung architectures. For lung function, resistance, compliance and TLC were evaluated using a forced oscillation technique. While baseline airway resistance did not change, elastance increased and TLC decreased especially for 0.5 ppm exposure (Figure 4, 5).

3. Development of a combustion particle generator for exposing animals to PM during development

Combustion particles for inhalation studies are generated using an ethylene-fueled burner that can be configured to generate different types of soot. Studies thus far have looked at soot from a diffusion flame where fuel is allowed to mix with a surrounding air flow and excess fuel that escapes from the flame is pyrolized into particulate matter composed almost entirely of elemental carbon. This particulate matter is then ported directly into an exposure chamber where it is mixed with clean air without the need for collecting and re-aerosolizing the particles. Particle concentration can be varied with fuel flow rate, and is held at a mass concentration of 50-80 μg/m3 for developmental studies, which translates to a number concentration of approximately 20,000 particles/cm³.

The same particle generator is capable of generating soot of different sizes and concentrations by operating in a premixed flame mode with an inert gas sheath surrounding the flame. Through careful controlling the fuel-air mixture and overall flow rate, it is possible to select a particular peak particle diameter within a range of 50-200 nanometers, to vary the concentration of the particles, and to vary the level of PAH produced in the flame. The burner development project has been jointly funded by Projects 1 and 5, and has been used for controlled exposures for both projects.

Expected Results:

Children and the elderly are thought to be the most susceptible to particulate air pollutant exposure. The elderly are more likely to have pre-existing impairments that make them more likely to suffer symptoms from inhaling particulates, and children respire much more than adults per unit of body mass due to their higher level of physical activity and greater time spent outdoors. The airways in children grow as their bodies grow, and, when exposed to air pollution, the airways appear to grow in ways that lead to diminished lung function. As a result, children who grow up with increased air pollution may be at higher risk when inhaling pollutants as adults. This project will quantify the amounts and kinds of pollutants that lead to airway impairment, determine when the airways are most easily impaired during their development, and identify which functions are impaired due to this exposure.

Future Activities:

We will analyze rat lungs exposed to particles of different compositions, and compare them to normal lungs. The first particle exposures have been completed and data analyses are currently underway.

Journal Articles on this Report : 4 Displayed | Download in RIS Format

Publications Views
Other subproject views:	All 21 publications	13 publications in selected types	All 13 journal articles
Other center views:	All 128 publications	71 publications in selected types	All 64 journal articles

Publications
Type	Citation	Sub Project	Document Sources
Journal Article	Lee DY, Wexler AS, Fanucchi MV, Plopper CG. Expiration rate drives human airway design. Journal of Theoretical Biology 2008;253(2):381-387.	R832414 (2009) R832414C005 (2008) R832414C005 (Final)	Abstract from PubMed Full-text: Science Direct - full text HTML Exit Abstract: Science Direct Exit Other: Science Direct - full text PDF Exit
Journal Article	Lee D, Park SS, Ban-Weiss GA, Fanucchi MV, Plopper CG, Wexler AS. Bifurcation model for characterization of pulmonary architecture. Anatomical Record 2008;291(4):379-389.	R832414 (2009) R832414C005 (2007) R832414C005 (2008) R832414C005 (Final)	Abstract from PubMed Full-text: Wiley Online - full text HTML Exit Abstract: Wiley Online Exit Other: Wiley Online - full text PDF Exit
Journal Article	Lee D, Fanucchi MV, Plopper CG, Fung J, Wexler AS. Pulmonary architecture in the conducting regions of six rats. Anatomical Record 2008;291(8):916-926.	R832414 (2009) R832414C005 (2008) R832414C005 (Final)	Abstract from PubMed Full-text: Wiley Online - full text HTML Exit Abstract: Wiley Online Exit Other: Wiley Online - full text PDF Exit
Journal Article	Tebockhorst S, Lee D, Wexler AS, Oldham MJ. Interaction of epithelium with mesenchyme affects global features of lung architecture: a computer model of development. Journal of Applied Physiology 2007;102(1):294-305.	R832414 (2009) R832414C005 (2007) R832414C005 (2008) R832414C005 (Final)	Abstract from PubMed Full-text: JAP-full text HTML Exit Abstract: JAP Exit Other: JAP-full text PDF Exit

Supplemental Keywords:

aerosol, asthma, ambient air, ozone, exposure, health effects, human health, metabolism, sensitive populations, infants, PAH, metals, oxidants, agriculture, transportation,, RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, ENVIRONMENTAL MANAGEMENT, Air, particulate matter, Environmental Chemistry, Health Risk Assessment, Risk Assessments, Biochemistry, Physical Processes, Risk Assessment, atmospheric particulate matter, children's health, particle deposition, acute cardiovascular effects, cardiopulmonary responses, chemical characteristics, human health effects, toxicology, airborne particulate matter, animal model, exposure, biological mechanisms, human exposure, PM, particulate matter components, exposure assessment, cardiovascular disease

Progress and Final Reports:

Original Abstract

Main Center Abstract and Reports:

R832414 Center for the Study of Metals in the Environment

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R832414C001 Project 1 -- Pulmonary Metabolic Response
R832414C002 Endothelial Cell Responses to PM—In Vitro and In Vivo
R832414C003 Project 3 -- Inhalation Exposure Assessment of San Joaquin Valley Aerosol
R832414C004 Project 4 -- Transport and Fate Particles
R832414C005 Project 5 -- Architecture Development and Particle Deposition

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.