This bioengineering interdisciplinary partnership project plans to use engineering expertise to develop a combination of tools, including computational fluid mechanics, the development of particle technology, and physiological approaches in animal models, to be utilized in a comprehensive study on particle deposition, retention, and clearance pathways in the developing lung. There is no more important imperative in our society than to protect the health of children, yet the specific differences in pulmonary structure between newborn, children, and adult lungs have not been addressed in assessing health risks associated with environmental exposure to aerosol particulates. Children's lungs postnatally undergo remarkable structural changes, such as a dramatic increase in alveolation, in addition to an increase in size. Our recent studies clearly indicate that the structure of the acinar airways has a profound influence on fine particle deposition. It is, therefore, very likely that particle deposition, retention, and clearance pathways in infants and young children are significantly different from those in adults. In particular, our preliminary data suggest that health risks may rise rapidly postnatally and peak between 2 and 5 years. However, little is known about the qualitative and quantitative aspects of particle deposition in developing lungs, mostly because these questions are not accessible to clinical studies or experimentation for ethical and technical reasons. We propose: (1) to establish computational fluid mechanics methods and investigate the effects of structural changes during lung development on deposition; (2) to develop a state-of-the-art high precision lung function/inhalation detection methodology utilizing engineered tracer particles; and (3) to apply this new methodology to investigate how particles are deposited and retained in the postnatally developing rat animal model. These proposed studies will allow us, for the first time, to get a comprehensive picture of changes in particle deposition-retention associated with lung development. This knowledge has important implications for the estimation of health hazards posed by particulate air pollution and for the establishment of age-appropriate doses of therapeutic drugs delivered by aerosols.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL070542-05
Application #
7274833
Study Section
Special Emphasis Panel (ZRG1-SSS-3 (50))
Program Officer
Blaisdell, Carol J
Project Start
2003-09-15
Project End
2009-08-31
Budget Start
2007-09-01
Budget End
2009-08-31
Support Year
5
Fiscal Year
2007
Total Cost
$577,655
Indirect Cost
Name
Harvard University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02115
Henry, Frank S; Tsuda, Akira (2016) Onset of alveolar recirculation in the developing lungs and its consequence on nanoparticle deposition in the pulmonary acinus. J Appl Physiol (1985) 120:38-54
Kojic, Milos; Filipovic, Nenad; Tsuda, Akira (2013) A mesoscopic bridging scale method for fluids and coupling dissipative particle dynamics with continuum finite element method. Comput Methods Appl Mech Eng 197:821-833
Tsuda, Akira; Henry, Frank S; Butler, James P (2013) Particle transport and deposition: basic physics of particle kinetics. Compr Physiol 3:1437-71
Kreyling, Wolfgang G; Semmler-Behnke, Manuela; Takenaka, Shinji et al. (2012) Differences in the Biokinetics of Inhaled Nano- versus Micrometer-Sized Particles. Acc Chem Res :
Henry, F S; Haber, S; Haberthür, D et al. (2012) The simultaneous role of an alveolus as flow mixer and flow feeder for the deposition of inhaled submicron particles. J Biomech Eng 134:121001
Semmler-Behnke, Manuela; Kreyling, Wolfgang G; Schulz, Holger et al. (2012) Nanoparticle delivery in infant lungs. Proc Natl Acad Sci U S A 109:5092-7
Schulz, Holger; Eder, Gunter; Bolle, Ines et al. (2012) Micron-sized intrapulmonary particle deposition in the developing rat lung. J Appl Physiol 112:759-65
Kojic, M; Butler, J P; Vlastelica, I et al. (2011) Geometric hysteresis of alveolated ductal architecture. J Biomech Eng 133:111005
Hirn, Stephanie; Semmler-Behnke, Manuela; Schleh, Carsten et al. (2011) Particle size-dependent and surface charge-dependent biodistribution of gold nanoparticles after intravenous administration. Eur J Pharm Biopharm 77:407-16
Tsuda, Akira; Laine-Pearson, Fiona E; Hydon, Peter E (2011) Why chaotic mixing of particles is inevitable in the deep lung. J Theor Biol 286:57-66

Showing the most recent 10 out of 38 publications