Basic knowledge of aerosol kinetics is essential for the understanding of many important physiological processes, such as environmental exposure to pathogenic particles, or therapeutic and diagnostic application of aerosol delivered substances. Our major goal is to understand aerosol behavior in the lung periphery. The currently existing mathematical models of aerosol transport and deposition consider the viscous flow reversible and, therefore, theoretically exclude the possibility of convective (flow-induced) mixing in the acinar region. Contrary to these theories, experimental data suggest appreciable convective mixing in the acinus. The recent discovery that viscous flow can be irreversible if the flow exhibits a chaotic structure (Ottino, et al., Nature, 333(6172),419-425, 1988) has opened up a new avenue in fluid mechanics, describing chaotic behavior of fluids as an important factor in mixing. Studying the influence of structural characteristics of the acinar duct, in particular the effects of time-dependent geometric expansion of alveolar walls on flow behavior, we have observed phenomena characteristic of chaotic flow. Based on these observations we hypothesize that complex chaotic flow can occur in the rhythmically expanding-contracting alveolated duct structure during normal breathing and it can result in strong flow-induced (chaotic) mixing. We propose to test this hypothesis with a combination of mathematical analyses - Lagrangian particle tracking and flow visualization in physical alveolus models and with animal lungs. We will quantify the extent of mixing by computing the time evolution of the entropy of tracer particles. This new concept leads to a totally different and quantifiable picture of the previously used ideas of spreading and dispersion. We believe that the results of this proposed study would give us new insight into aerosol kinetics and would help us in understanding important physiological processes.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL054885-04
Application #
2750493
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1995-08-18
Project End
2000-07-31
Budget Start
1998-08-01
Budget End
1999-07-31
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Harvard University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
082359691
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
Filipovic, Nenad; Gibney, Barry C; Nikolic, Dalibor et al. (2014) Computational analysis of lung deformation after murine pneumonectomy. [corrected]. Comput Methods Biomech Biomed Engin 17:838-44
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
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
Butler, James P; Loring, Stephen H; Patz, Samuel et al. (2012) Evidence for adult lung growth in humans. N Engl J Med 367:244-7
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
Kojic, M; Butler, J P; Vlastelica, I et al. (2011) Geometric hysteresis of alveolated ductal architecture. J Biomech Eng 133:111005
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
Butler, James P; Tsuda, Akira (2011) Transport of gases between the environment and alveoli--theoretical foundations. Compr Physiol 1:1301-16

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