: The deposition of small (less than 2.5Mm) particles in the human lung is governed primarily by the mechanisms of sedimentation and diffusion. Recent studies we performed in the microgravity (MG) environment have shown a significant degree of enhanced deposition of small particles, compared to that predicted by existing numerical models of deposition. It seems likely that this results from the previously unaccounted for effects of the non-reversibility of flows in the human lung (effectively providing enhanced diffusion). Such enhanced deposition means that existing models for small particles (less than 2.5 Mm) probably underestimate exposure, and that this increased exposure occurs in the sensitive alveolar regions of the lung. We propose to investigate enhanced alveolar deposition by studying 1) The contribution of diffusion to aerosol dispersion by inclusion of breathhold in aerosol bolus tests: 2) The increase in convective mixing in the lung caused by flow reversals that induces complex mixing of the streamlines in the lung; and 3) The increase in convective mixing in the lung in 1G by performing similar studies using the smallest particles on the ground. To study these effects, we propose to measure regional deposition and dispersion of inhaled boluses of 0.5 and 2 micron particles in MG in the NASA KC-135 Microgravity research Aircraft, and 0.5 micron particles on the ground. By performing these studies in the absence of gravity we will be able to directly study these effects without the confounding influence of sedimentation, a gravitational process. Such direct observations without the influence of sedimentation are not possible in the terrestrial laboratory. There is evidence for many lung diseases beginning in the small airways or alveoli, and increased alveolar deposition through enhanced diffusion may provide a link between long-term MG exposure and lung disease. The results of this study will allow existing models of regional intrapulmonary aerosol deposition to be improved, especially for the smaller particles (those in the range 0.5 to 1 micron). Such information will provide a much-improved basis for the assessment of exposure to small inhaled particles both in long duration spaceflight and on Earth.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
1R01ES011184-01A1
Application #
6467616
Study Section
Respiratory Physiology Study Section (RESP)
Program Officer
Mastin, Patrick
Project Start
2002-05-06
Project End
2004-03-31
Budget Start
2002-05-06
Budget End
2003-03-31
Support Year
1
Fiscal Year
2002
Total Cost
$315,000
Indirect Cost
Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Prisk, G Kim; Sá, Rui Carlos; Darquenne, Chantal (2013) Cardiogenic mixing increases aerosol deposition in the human lung in the absence of gravity. Acta Astronaut 92:15-20
Peterson, Jonathan B; Prisk, G Kim; Darquenne, Chantal (2008) Aerosol deposition in the human lung periphery is increased by reduced-density gas breathing. J Aerosol Med Pulm Drug Deliv 21:159-68
Darquenne, Chantal; Prisk, G Kim (2005) Aerosols in the study of convective acinar mixing. Respir Physiol Neurobiol 148:207-16
Darquenne, Chantal; Prisk, G Kim (2004) Aerosol deposition in the human respiratory tract breathing air and 80:20 heliox. J Aerosol Med 17:278-85
Darquenne, Chantal; Prisk, G Kim (2004) Effect of small flow reversals on aerosol mixing in the alveolar region of the human lung. J Appl Physiol 97:2083-9