Final Report: Assessing Deposition of Ambient Particles in the Lung

EPA Grant Number: R827353C009
Subproject: this is subproject number 009 , established and managed by the Center Director under grant R827353
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: EPA Harvard Center for Ambient Particle Health Effects
Center Director: Koutrakis, Petros
Title: Assessing Deposition of Ambient Particles in the Lung
Investigators: Godleski, John J. , Tsuda, Akira
Institution: Harvard University
EPA Project Officer: Chung, Serena
Project Period: June 1, 1999 through May 31, 2005 (Extended to May 31, 2006)
Project Amount: Refer to main center abstract for funding details.
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text |  Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air

Objective:

Theme III: Biological Mechanisms/Dosimetry: Theme III focused upon mechanisms of cardiac vulnerability as a result of air pollution exposure. Many of our concentrated ambient particles (CAPs) animal toxicology and human panel studies have linked pulmonary and cardiovascular health outcomes to different particulate matter (PM) components such as trace metals, elemental carbon, sulfates and silicon (Batalha, et al., 2002; Clarke, et al., 2000; Saldiva, et al., 2002). Reanalysis of the Harvard Six Cities study provided strong evidence of increased toxicity associated with combustion-related PM from traffic and power plants compared to soil dust (Laden, et al., 2000).

The objectives of Theme III were to identify the particulate and gaseous air pollutants responsible for increased cardiac vulnerability as an adverse health effect and to define the biological mechanisms that lead to this outcome. As part of this theme, we specifically worked to: (1) identify the physical and chemical properties of particulate matter responsible for the observed adverse health effects; (2) determine whether gaseous co-pollutants exacerbate the effects of particles; (3) investigate the biological mechanisms by which particulate matter produces mortality and acute or chronic morbidity; and (4) examine particle deposition patterns and fate in the respiratory tract. These objectives were addressed in several areas of research that explored the components of air pollution that cause adverse health effects and the biological mechanisms that may lead to fatal outcomes. The projects under this theme built upon the findings from a number of our previous animal studies, which made it possible to explore and define both cardiac and pulmonary responses to inhaled fly ash and concentrated ambient particles (Killingsworth, et al., 1997).

Center activities focused on the development of theoretical models to predict PM deposition as a function of particle size (Tsuda, et al., 2002; Henry, et al., 2002; Haber, et al., 2003). Subsequently, a series of human ambient particle deposition studies were conducted (Montoya, et al., 2004).

Summary/Accomplishments (Outputs/Outcomes):

In Tsuda, et al. (2002), we demonstrated, through flow visualization studies in rhythmically ventilated rat lungs, that chaotic mixing may be key to aerosol transport in the lungs. We found substantial alveolar flow irreversibility with stretched and folded fractal patterns, which led to a sudden increase in mixing. These findings support the theory that chaotic alveolar flow governs gas kinematics in the lung periphery, and hence the transport, mixing, and ultimately the deposition of fine aerosols.

In Henry, et al. (2002), we described the behavior of fluid particles (or bolus) in a realistic, numerical, alveolated duct model with rhythmically expanding walls. We found acinar flow exhibiting multiple saddle points, characteristic of chaotic flow, resulting in substantial flow irreversibility. Computations of axial variance of bolus spreading indicated that the growth of the variance with respect to time is faster than linear, a finding inconsistent with dispersion theory. Lateral behavior of the bolus shows fine-scale, stretch-and-fold striations, exhibiting fractal-like patterns with a fractal dimension of 1.2, which compares well with the fractal dimension of 1.1 observed in our experimental studies performed with rat lungs. We concluded that kinematic irreversibility of acinar flow due to chaotic flow may be the dominant mechanism of aerosol transport deep in the lungs.

In Haber, et al. (2003) we tested the hypothesis that the trajectories and deposition of aerosols inside the alveoli differ substantially from those previously predicted. To test this hypothesis, trajectories of fine particles (0.5–2.5 μm in diameter) moving in the foregoing alveolar flow field and simultaneously subjected to the gravity field were simulated. The results show that alveolar wall motion is crucial in determining the enhancement of aerosol deposition inside the alveoli. In particular, 0.5- to 1-μm-diameter particles are sensitive to the detailed alveolar flow structure (e.g., recirculating flow), as they undergo gravity-induced convective mixing and deposition. Accordingly, deposition concentrations within each alveolus are nonuniform, with preferentially higher densities near the alveolar entrance ring, consistent with physiological observations. Deposition patterns along the acinar tree are also nonuniform, with higher deposition in the first half of the acinar generations. This is a result of the combined effects of enhanced alveolar deposition in the proximal region of the acinus due to alveoli expansion and contraction and reduction in the number of particles remaining in the gas phase down the acinar tree. We concluded that the cyclically expanding and contracting motion of alveoli plays an important role in determining gravitational deposition in the pulmonary acinus.

In addition, we conducted a series of exposure experiments to test the hypothesis that the lung deposition of ambient particles (i.e., CAPs) can not be adequately described based on findings with conventionally used ‘test particles’ such as iron oxide particles because of the complex physicochemical properties of CAPs. In the course of eight experiments performed so far, dogs were exposed to CAPs and control particles (iron oxide, mean diameter of 0.7 μm) and the total deposition of these particles was computed and compared over a wide range of particle size (40 nm–3 μm). The initial results showed that: (1) changes in relative humidity along the airways influenced CAPs characteristics and consequently their behavior in the respiratory tract; and (2) the total deposition of CAPs was substantially higher than that of control particles. These results suggest that the hygroscopic properties of CAPs may be important in determining deposition, and that the estimation based on nonhygroscopic control particles could substantially underestimate the particle deposition for a given exposure.

The total deposition fraction of fine and ultrafine aerosols was measured in a group of six healthy adults exposed to Boston ambient particles. During these exposures particle mass and number concentration ranged from 7 and 32 μg/m3 and from 16,100 and 64,100 /cm3, respectively. Fifteen repeated inhalation-exhalation cycles were conducted during a given exposure session. The deposition efficiency of particles ranging from 40 to 2045 nm was determined using the average concentration of inhaled and exhaled particles measured during these cycles. Deposition efficiencies ranged between 7.3 ± 18.7% (for particles 168–195 nm) and 98.6 ± 28.1% (for particles 1545–2045 nm). Subjects exhibited similar deposition patterns with a minimum efficiency in the size range of 100–200 nm. Results from analysis of variance and mixed model regressions, suggested that deposition efficiency varied with individual and particle size. Deposition efficiencies varied mostly among subjects for particles in the size range between 100 and 1000 nm. Measured deposition efficiencies were compared to those reported by the International Commission on Radiological Protection (ICRP) model. For this comparison, the ICRP deposition efficiencies for a sitting female subject were used. The minimum deposition estimated by the model was at 400–500 nm, while our results show a minimum at about 100 nm. The ICRP model deposition efficiencies were lower for particles < 150 nm, about 20%, and higher for particles > 676 nm by about 20%. Inter-subject variability in airway morphology, differences in breathing patterns used in the model and, particle composition may account for the observed differences. This work was published in Montoya, et al. (2004).

Conclusions:

Although acinar flow patterns likely have little effect on the gas exchange processes of highly diffusible respiratory gases (O2 and CO2), they play an important role in determining the fate of inhaled fine particles with low diffusivity and little gravitational sedimentation. We conclude that chaotic acinar flow may be the origin of substantial mixing and transport of fine aerosols deep in the lung.

References:

Batalha JRF, Saldiva PHN, Clarke RW, Coull BA, Stearns RC, Lawrence J, Krishna Murthy GG, Koutrakis P, Godleski JJ. Concentrated ambient air particles induce vasoconstriction of small pulmonary arteries in rats. Environmental Health Perspectives 2002;110(12):1191-1197.

Clarke RW, Coull BA, Reinisch U, Catalano P, Killingsworth CR, Koutrakis P, Kavouras I, Krishna Murthy GG, Lawrence J, Lovett EG, Wolfson JM, Verrier RL, Godleski JJ. Inhaled concentrated ambient particles are associated with hematologic and bronchoalveolar lavage changes in canines. Environmental Health Perspectives 2000;108(12):1179-1187.

Haber S, Yitzhak D, Tsuda A. Gravitational deposition in a rhythmically expanding and contracting alveolus. Journal of Applied Physiology 2003;95(2):657-671.

Henry FS, Butler JP, Tsuda A. Kinematically irreversible acinar flow: a departure from classical dispersive aerosol transport theories. Journal of Applied Physiology 2002;92:835-845.

Killingsworth C, Alessandrini F, Murthy G, Catalano P, Paulauskis J, Godleski J. Inflammation, chemokine expression, and death in monocrotaline-treated rats following fuel oil fly ash inhalation. Inhalation Toxicology 1997;9:541-565.

Laden F, Neas L, Dockery D, Schwartz J. Association of fine particulate matter from different sources with daily mortality in six U.S. cities. Environmental Health Perspectives 2000;108(10):941-947.

Montoya L, Lawrence J, Krishna Murthy GG, Sarnat J, Godleski J, Koutrakis P. Continuous measurements of ambient particle deposition in human subjects. Aerosol Science and Technology 2004;38(10):980-990.

Saldiva PH, Clarke RW, Coull BA, Stearns RC, Lawrence J, Koutrakis P, Suh H, Tsuda A, Godleski JJ. Acute pulmonary inflammation induced by concentrated ambient air particles is related to particle composition. American Journal of Respiratory and Critical Care Medicine 2002;165(12):1610-1617.

Tsuda A, Rogers RA, Hydon PE, Butler JP. Chaotic mixing deep in the lung. Proceedings of the National Academy of Sciences of the United States of America 2002;99(15):10173-10178.


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

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Journal Article Haber S, Yitzhak D, Tsuda A. Gravitational deposition in a rhythmically expanding and contracting alveolus. Journal of Applied Physiology 2003;95(2):657-671. R827353 (Final)
R827353C009 (2002)
R827353C009 (Final)
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  • Journal Article Henry FS, Butler JP, Tsuda A. Kinematically irreversible acinar flow:a departure from classical dispersive aerosol transport theories. Journal of Applied Physiology 2002;92(2):835-845. R827353 (Final)
    R827353C009 (2002)
    R827353C009 (Final)
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  • Journal Article Montoya L, Lawrence J, Krishna Murthy G, Sarnat J, Godleski J, Koutrakis P. Continuous measurements of ambient particle deposition in human subjects. Aerosol Science and Technology 2004;38(10):980-990. R827353 (Final)
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  • Journal Article Tsuda A, Rogers RA, Hydon PE, Butler JP. Chaotic mixing deep in the lung. Proceedings of the National Academy of Sciences of the United States of America 2002;99(15):10173-10178. R827353 (Final)
    R827353C009 (Final)
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  • Supplemental Keywords:

    RFA, Health, Scientific Discipline, Air, particulate matter, Toxicology, air toxics, Environmental Chemistry, Epidemiology, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Environmental Microbiology, genetic susceptability, indoor air, Molecular Biology/Genetics, Biology, ambient air quality, health effects, monitoring, risk assessment, sensitive populations, particulates, chemical exposure, interindividual variability, molecular epidemiology, air pollutants, exposure and effects, stratospheric ozone, ambient air monitoring, health risks, cardiopulmonary responses, indoor exposure, human health effects, COPD, ambient air, developmental effects, epidemelogy, respiratory disease, exposure, pulmonary disease, ambient measurement methods, ambient monitoring, air pollution, particle exposure, biological mechanism , Human Health Risk Assessment, human exposure, heart rate, inhalation, pulmonary, ambient particle health effects, cardiopulmonary response, particulate exposure, inhaled, inhalation toxicology, human susceptibility, PM, cardiopulmonary, human health, indoor air quality, inhaled particles, toxics, metals, respiratory, genetic susceptibility, air quality, dosimetry, cardiovascular disease, human health risk

    Relevant Websites:

    http://www.hsph.harvard.edu/epacenter/epa_center_99-05/index.html Exit

    Progress and Final Reports:

    Original Abstract
  • 1999 Progress Report
  • 2000 Progress Report
  • 2001 Progress Report
  • 2002 Progress Report
  • 2003
  • 2004

  • Main Center Abstract and Reports:

    R827353    EPA Harvard Center for Ambient Particle Health Effects

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R827353C001 Assessing Human Exposures to Particulate and Gaseous Air Pollutants
    R827353C002 Quantifying Exposure Error and its Effect on Epidemiological Studies
    R827353C003 St. Louis Bus, Steubenville and Atlanta Studies
    R827353C004 Examining Conditions That Predispose Towards Acute Adverse Effects of Particulate Exposures
    R827353C005 Assessing Life-Shortening Associated with Exposure to Particulate Matter
    R827353C006 Investigating Chronic Effects of Exposure to Particulate Matter
    R827353C007 Determining the Effects of Particle Characteristics on Respiratory Health of Children
    R827353C008 Differentiating the Roles of Particle Size, Particle Composition, and Gaseous Co-Pollutants on Cardiac Ischemia
    R827353C009 Assessing Deposition of Ambient Particles in the Lung
    R827353C010 Relating Changes in Blood Viscosity, Other Clotting Parameters, Heart Rate, and Heart Rate Variability to Particulate and Criteria Gas Exposures
    R827353C011 Studies of Oxidant Mechanisms
    R827353C012 Modeling Relationships Between Mobile Source Particle Emissions and Population Exposures
    R827353C013 Toxicological Evaluation of Realistic Emissions of Source Aerosols (TERESA) Study
    R827353C014 Identifying the Physical and Chemical Properties of Particulate Matter Responsible for the Observed Adverse Health Effects
    R827353C015 Research Coordination Core
    R827353C016 Analytical and Facilities Core
    R827353C017 Technology Development and Transfer Core