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Project Title:  Clearance of Particles Depositing in the Human Lung in Low Gravity Reduce
Fiscal Year: FY 2013 
Division: Human Research 
Research Discipline/Element:
HRP SHFH:Space Human Factors & Habitability (archival in 2017)
Start Date: 06/01/2008  
End Date: 11/30/2012  
Task Last Updated: 04/04/2013 
Download report in PDF pdf
Principal Investigator/Affiliation:   Prisk, G. Kim Ph.D., D.Sc. / University of California, San Diego 
Address:  Department of Medicine 
9500 Gilman Drive 
La Jolla , CA 92093-0852 
Email: kprisk@ucsd.edu 
Phone: 858-534-3233  
Congressional District: 53 
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of California, San Diego 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Bennett, William  University of North Carolina at Chapel Hill 
Darquenne, Chantal  University of California, San Diego 
Project Information: Grant/Contract No. NCC 9-58-HFP01604 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2007 Crew Health NNJ07ZSA002N 
Grant/Contract No.: NCC 9-58-HFP01604 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) SHFH:Space Human Factors & Habitability (archival in 2017)
Human Research Program Risks: (1) Dust:Risk of Adverse Health & Performance Effects of Celestial Dust Exposure (IRP Rev F)
(2) ExMC:Risk of Unacceptable Health and Mission Outcomes Due to Limitations of In-flight Medical Capabilities (IRP Rev E)
Human Research Program Gaps: (1) AEH Watch Item/NSBRI Research:What are the effects of lunar gravity on permissible exposure limits for inhalation of lunar dust? (Closed as of IRP Rev J)
(2) AEH02:What is the toxicity of lunar dust in the respiratory system? (Closed as of IRP Rev J)
(3) AEH05:What are the permissible exposure limits for inhalation of lunar dust? (Closed as of IRP Rev J)
(4) ExMC 4.26:We do not have the capability to screen for, diagnose, and treat disease due to dust exposure during exploration missions (IRP Rev E)
Task Description: Main Findings:

In this final year of the project we have finally succeeded in flying the planned experiment in the week August 29 – September 2, 2011. This happened only through extraordinary efforts on our part to secure a week of flight at greatly increased cost. Our progress can be summarized as follows:

• 1 week of flights (4) successfully performed • 5 high quality data sets out of a possible 8 collected • Gamma camera hardware worked with no anomalies • Minor nebulizer leak on flight 1 – resolved. • Low nebulizer output on flight 3 – cause undetermined, not repeated • Several further attempts at reflight unsuccessful • Successful completion of studies using 4-micron droplets • Studies using 1-micron droplet unable to be manifested • Publication submitted and favorably reviewed, under revision

Recommendation: This project has been hampered by the current NASA approach to funding aircraft access involving full payment of flight costs in advance, with costs spread across the payload elements, and with no agency input of backup funding. This produces an unstable condition where a single customer backing out of a flight week raises costs on all others, with resulting further withdrawals, and a cancellation of the flight week. Flight costs need to be considered as a programmatic cost, just as expenses such as beam time at Brookhaven, or the running cost of the bed-rest facility are covered by the program, as opposed to the project.

Research Impact/Earth Benefits: Airborne particulate matter is a health hazard. The deposition of particulate matter (PM, often referred to as aerosols) in the human lung is known to bring with it both long-term and short-term adverse health consequences. On Earth, effects of PM-induced lung injury are most readily seen in individuals with pre-existing lung disease (i.e. asthma, chronic obstructive pulmonary disease). Studies suggest that particle-induced inflammation or edema likely enhance underlying pulmonary disease, leading to a worsening of already abnormal pulmonary ventilation/perfusion relationships and gas exchange. Such worsening can result in hypoxemia leading to fatal cardiac arrhythmia. There is also little question that even healthy individuals exposed to PM for extended periods are susceptible to PM-induced lung injury. For example, the increase in risk of death from long-term exposure to PM in six US cities has been shown to be in the area of 17% for the general population for a modest increase in total PM load of 24.5 micro-g/m3. These studies will directly determine the consequences of a more peripheral site of aerosol deposition on the subsequent clearance of PM from the lung. It is well established that the negative health consequences of exposure to environmental PM increase as particle size is reduced. These studies will provide insight into how much of this effect is a consequence of the increased residence time of particles that are deposited more peripherally in the lungs. Such peripheral deposition occurs not only on the Lunar surface but here on Earth.

Task Progress & Bibliography Information FY2013 
Task Progress: This section on task progress deals with the technical aspects of the program. The reader is referred to the Main findings section for Scientific Progress (See Task Description section above).

Flight Scheduling Progress

Leading up to year 4 of this project, the project had been hamstrung by the problems directly stemming from changes in the NASA policy for accessing the reduced gravity aircraft. In brief, we attempted to fly multiple times with NASA without success. We instituted an attempt to fly the experiment on the European A300, securing European Space Agency (ESA) approval for those flights. After considerable effort this was abandoned in Feb 2011. At the time of the last progress report (April 2011) we articulated our contingency plans for ensuring scientific return from this project in the face of flight difficulties. Our preferred approach (Plan A) was a week of flights in July 2011 and a second week (date TBD). Our second approach (Plan B) was to buy the plane for a single week of flights. This approach had the advantage of flight certainty, but the significant disadvantage of reducing us to a single flight week (based on cost). When the July 2011 flight opportunity offered as part of the FAST program disappeared we opted for Plan B. In order to accomplish this we joined forces with a NASA investigator (Dr. Mark Shelhammer, Johns Hopkins) who was facing similar difficulties in terms of scheduling flights. Between us, we were able to commit a sufficient amount of flight money to guarantee a 3-day flight week (our absolute minimum requirement). Once we committed to this, other customers wanting fewer flight resources came on board because there was certainty the flights would occur. The effect of this was to increase the money pool to a level sufficient to allow a 4-flight week. In the week of August 29 to September 2, 2011 we finally succeeded in flying the experiment using the 4-micron particle size droplets. We subsequently learned of a further pathway to flight via the NASA Flight Opportunities (FO) program. We positioned ourselves for this opportunity, but when the FO program solicitation was released in April 2012, parabolic flight support was (to our great surprise, given previous discussions) explicitly excluded, making this pathway unavailable to us. We have on several occasions explored further routine flight opportunities through NASA Life Sciences (the standard path) with nothing forthcoming. In summary, we have succeeded in completing a 4-flight week of activities in August-Sept 2011. Further attempts to fly have been unsuccessful.

Bibliography Type: Description: (Last Updated: 03/11/2021)  Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Darquenne C, Zeman KL, Sa RC, Cooper TK, Fine JM, Bennett WD, Prisk GK. "Removal of sedimentation decreases deposition of coarse particles in the lung periphery, reducing retention." 2013 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-14, 2013.

2013 NASA Human Research Program Investigators’ Workshop, Galveston, TX, February 12-14, 2013. , Feb-2013

Articles in Peer-reviewed Journals Darquenne C. "Aerosol deposition in the human lung in reduced gravity." J Aerosol Med Pulm Drug Deliv. 2014 Jun;27(3):170-7. Review. http://dx.doi.org/10.1089/jamp.2013.1079 ; PubMed PMID: 24870702; PubMed Central PMCID: PMC4088354 , Jun-2014
Articles in Peer-reviewed Journals Lejeune L, Caiani EG, Prisk GK, Migeotte PF. "Evaluation of ensemble averaging methods in 3D ballistocardiography. " Conf Proc IEEE Eng Med Biol Soc. 2014 Aug;2014:5176-9. https://doi.org/10.1109/EMBC.2014.6944791 ; PubMed PMID: 25571159 , Aug-2014
Articles in Peer-reviewed Journals Prisk GK. "Microgravity and the respiratory system." Eur Respir J. 2014 May;43(5):1459-71. Epub 2014 Mar 6. Review. https://doi.org/10.1183/09031936.00001414 ; PubMed PMID: 24603820 , May-2014
Articles in Peer-reviewed Journals Migeotte PF, Lejeune L, Delière Q, Caiani E, Casellato C, Tank J, Funtova I, Baevsky R, Prisk GK, van de Borne P. "Three dimensional Ballistocardiogram and Seismocardiogram: what do they have in common?" Conf Proc IEEE Eng Med Biol Soc. 2014;2014:6085-8. https://doi.org/10.1109/EMBC.2014.6945017 ; PMID: 25571385 , Aug-2014
Articles in Peer-reviewed Journals Lejeune L, Prisk GK, Nonclercq A, Migeotte PF. "MRI-based aortic blood flow model in 3D ballistocardiography." Conf Proc IEEE Eng Med Biol Soc. 2015 Aug;2015:7171-4. https://doi.org/10.1109/EMBC.2015.7320046 ; PMID: 26737946 , Aug-2015
Articles in Peer-reviewed Journals Sá RC, Zeman KL, Bennett WD, Prisk GK, Darquenne C. "Effect of posture on regional deposition of coarse particles in the healthy human lung." J Aerosol Med Pulm Drug Deliv. 2015 Dec;28(6):423-31. Epub 2015 Mar 31. https://doi.org/10.1089/jamp.2014.1189 ; PMID: 25826480 , Dec-2015
Articles in Peer-reviewed Journals Sá RC, Zeman KL, Bennett WD, Prisk GK, Darquenne C. "Regional ventilation is the main determinant of alveolar deposition of coarse particles in the supine healthy human lung during tidal breathing." J Aerosol Med Pulm Drug Deliv. 2017 Oct;30(5):322-31. Epub 2017 Mar 9. https://doi.org/10.1089/jamp.2016.1336 ; PMID: 28277885; PMCID: PMC5650708 , Oct-2017
Articles in Peer-reviewed Journals Asadi AK, Sá RC, Arai TJ, Theilmann RJ, Hopkins SR, Buxton RB, Prisk GK. "Regional pulmonary perfusion patterns in humans are not significantly altered by inspiratory hypercapnia." J Appl Physiol (1985). 2019 Aug 1;127(2):365-75. https://doi.org/10.1152/japplphysiol.00254.2018 ; PMID: 31169470; PMCID: PMC6732437 , Aug-2019
Articles in Peer-reviewed Journals Prisk GK. "Pulmonary challenges of prolonged journeys to space: taking your lungs to the moon." Med J Aust. 2019 Sep;211(6):271-6. https://doi.org/10.5694/mja2.50312 ; PMID: 31420881; PMCID: PMC6745695 , Sep-2019
Articles in Peer-reviewed Journals Inan OT, Migeotte PF, Park KS, Etemadi M, Tavakolian K, Casanella R, Zanetti J, Tank J, Funtova I, Prisk GK, Di Rienzo M. "Ballistocardiography and seismocardiography: a review of recent advances." IEEE J Biomed Health Inform. 2015 Jul;19(4):1414-27. Epub 2014 Oct 7. https://doi.org/10.1109/JBHI.2014.2361732 ; PMID: 25312966 , Jul-2015
Articles in Peer-reviewed Journals Darquenne C, Prisk GK. "Particulate deposition in the human lung under lunar habitat conditions." Aviat Space Environ Med. 2013 Mar;84(3):190-5. PubMed PMID: 23513279 , Mar-2013
Articles in Peer-reviewed Journals Prisk GK, Sa RC, Darquenne C. "Cardiogenic mixing increases aerosol deposition in the human lung in the absence of gravity." Acta Astronautica. In Press, Corrected Proof. Available online 12 June 2012. http://dx.doi.org/10.1016/j.actaastro.2012.05.022 , Jun-2012
Articles in Peer-reviewed Journals Henderson AC, Sa RC, Barash IA, Holverda S, Buxton RB, Hopkins SR, Prisk GK. "Rapid intravenous infusion of 20 mL/kg saline alters the distribution of perfusion in healthy supine humans." Respir Physiol Neurobiol. 2012 Mar 15;180(2-3):331-41. Epub 2011 Dec 31. http://dx.doi.org/10.1016/j.resp.2011.12.013 ; PubMed PMID: 22227320 , Mar-2012
Articles in Peer-reviewed Journals Linnarsson D, Carpenter J, Fubini B, Gerde P, Karlsson LL, Loftus DJ, Prisk GK, Staufer U, Tranfield EM, van Westrenen W. "Toxicity of lunar dust." Planetary and Space Science. 2012 Dec;74(1):57-71. http://dx.doi.org/10.1016/j.pss.2012.05.023 , Jul-2012
Articles in Peer-reviewed Journals Migeotte PF, De Ridder S, Tank J, Pattyn N, Funtova I, Baevsky R, Neyt X, Prisk GK. "Three dimensional ballisto- and seismo-cardiography: HIJ wave amplitudes are poorly correlated to maximal systolic force vector." Conf Proc IEEE Eng Med Biol Soc. 2012;2012:5046-9. http://dx.doi.org/10.1109/EMBC.2012.6347127 ; PubMed PMID: 23367062 (EMBC 2012. 2012 Annual International Conference of the IEEE Engineering in Medicine and Biology Society, San Diego, CA, Aug. 28-Sept. 1 2012.) , Oct-2012
Articles in Peer-reviewed Journals Migeotte PF, Tank J, Pattyn N, Funtova I, Baevsky R, Neyt X, Prisk GK. "Three dimensional ballistocardiography: methodology and results from microgravity and dry immersion." Conf Proc IEEE Eng Med Biol Soc. 2011;2011:4271-4. http://dx.doi.org/10.1109/IEMBS.2011.6091060 ; PubMed PMID: 22255283 (EMBC 2011. 2011 Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Boston, MA, Aug. 30 2011-Sept. 3 2011.) , Aug-2011
Articles in Peer-reviewed Journals De Ridder S, Migeotte PF, Neyt X, Pattyn N, Prisk GK. "Three-dimensional ballistocardiography in microgravity: a review of past research." Conf Proc IEEE Eng Med Biol Soc. 2011;2011:4267-70. http://dx.doi.org/10.1109/IEMBS.2011.6091059 ; PubMed PMID: 22255282 (EMBC 2011. 2011 Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Boston, MA, Aug. 30-Sept. 3 2011.) , Aug-2011
Articles in Peer-reviewed Journals Asadi AK, Cronin MV, Sá RC, Theilmann RJ, Holverda S, Hopkins SR, Buxton RB, Prisk GK. "Spatial-temporal dynamics of pulmonary blood flow in the healthy human lung in response to altered FI(O2)." J Appl Physiol. 2013 Jan 1;114(1):107-18. Epub 2012 Oct 25. http://dx.doi.org/10.1152/japplphysiol.00433.2012 ; PubMed PMID: 23104691 , Jan-2013
Awards Prisk GK. "ARTP Lifetime achievement award for services to respiratory science, January 2012." Jan-2012
Project Title:  Clearance of Particles Depositing in the Human Lung in Low Gravity Reduce
Fiscal Year: FY 2011 
Division: Human Research 
Research Discipline/Element:
HRP SHFH:Space Human Factors & Habitability (archival in 2017)
Start Date: 06/01/2008  
End Date: 05/31/2012  
Task Last Updated: 05/04/2011 
Download report in PDF pdf
Principal Investigator/Affiliation:   Prisk, G. Kim Ph.D., D.Sc. / University of California, San Diego 
Address:  Department of Medicine 
9500 Gilman Drive 
La Jolla , CA 92093-0852 
Email: kprisk@ucsd.edu 
Phone: 858-534-3233  
Congressional District: 53 
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of California, San Diego 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Bennett, William  University of North Carolina at Chapel Hill 
Darquenne, Chantal  University of California, San Diego 
Project Information: Grant/Contract No. NCC 9-58-HFP01604 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2007 Crew Health NNJ07ZSA002N 
Grant/Contract No.: NCC 9-58-HFP01604 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) SHFH:Space Human Factors & Habitability (archival in 2017)
Human Research Program Risks: (1) Dust:Risk of Adverse Health & Performance Effects of Celestial Dust Exposure (IRP Rev F)
(2) ExMC:Risk of Unacceptable Health and Mission Outcomes Due to Limitations of In-flight Medical Capabilities (IRP Rev E)
Human Research Program Gaps: (1) AEH Watch Item/NSBRI Research:What are the effects of lunar gravity on permissible exposure limits for inhalation of lunar dust? (Closed as of IRP Rev J)
(2) AEH02:What is the toxicity of lunar dust in the respiratory system? (Closed as of IRP Rev J)
(3) AEH05:What are the permissible exposure limits for inhalation of lunar dust? (Closed as of IRP Rev J)
(4) ExMC 4.26:We do not have the capability to screen for, diagnose, and treat disease due to dust exposure during exploration missions (IRP Rev E)
Task Description: Original Aims:

The deposition of particulate matter (PM) in the human lung is known to bring with it both long-term and short-term adverse health consequences. The deposition of particles in the lung is strongly influenced by gravitational sedimentation. Studies by our group have shown that normal gravity provides a screening effect whereby inhaled PM larger than 0.5 micron is mainly deposited in the larger airways where it is cleared by mucociliary clearance transport within ~one day. However in low-gravity, such as that on the surface of the Moon (~1/6G) and Mars (~3/8G), this protective 'gravitational screening' is less efficient, and as a result particles are deposited in the sensitive alveolar regions of the lung where residence times are very much longer. Further, there is evidence that the dust present on the surface of the Moon may possess potent toxicological properties. We hypothesize that clearance rates from the lung of particles deposited in low-gravity will be substantially reduced compared to that in 1G, resulting in increased residence times of these particles in the periphery of the lung, enhancing their potential to cause lung damage. In order to test this hypothesis we propose to measure the clearance rates (measured in 1G) over a few hours to ~1-2 days, of radio-labeled particles deposited in healthy humans both in 1G and in low-gravity corresponding to the lunar surface (~1/6G) during parabolic flight. These data will provide a comprehensive assessment of alterations in the clearance rate of particles inhaled under normal 1G conditions compared to particles inhaled under conditions of lunar gravity (1/6G). Such an assessment is needed to determine the degree of effort and cost required to control lunar dust within a planned lunar outpost.

Key Findings:

In this third year of the project we have completed all technical requirements for flight and stand ready to fly. However flight scheduling has been once again virtually impossible. As a consequence we have performed some ground studies in advance of flight studies. These are part of the post-doctoral fellowship work of Dr. Rui-Carlo Sa. In addition we attempted to manifest the experiment on the ESA/Novespace A-300 flying out of Bordeaux, France. However the difficulties with the French nuclear regulatory authorities to fly the necessary radioactive tracer proved insurmountable. The details of our activities can be found in the "Task Progress" section of the report.

Our current status can be summarized as follows:

- CPHS/Radiation approval in place

- Subject certifications complete

- Hardware and procedures fully tested and functional

- Structural issues resolved

- Ready for flight

- Waiting on flight manifesting, which we are informed will not be before July 2011.

Year 4 Plan:

We hope to fly both the 4 micron particle size objective AND the 1 micron particle size objective in Year 4 of the project. In response to the extreme difficulty experienced in scheduling reduced gravity flights, we devised and have now fully verified (as part of the ground studies performed for Dr. Sa's studies) a 2-subject-per-flight experimental structure that will permit more efficient use of scarce reduced gravity flight opportunities.

Research Impact/Earth Benefits: Airborne particulate matter is a health hazard.

The deposition of particulate matter (PM, often referred to as aerosols) in the human lung is known to bring with it both long-term and short-term adverse health consequences. On Earth, effects of PM-induced lung injury are most readily seen in individuals with pre-existing lung disease (i.e. asthma, chronic obstructive pulmonary disease). Studies suggest that particle-induced inflammation or edema likely enhance underlying pulmonary disease, leading to a worsening of already abnormal pulmonary ventilation/perfusion relationships and gas exchange. Such worsening can result in hypoxemia leading to fatal cardiac arrhythmia. There is also little question that even healthy individuals exposed to PM for extended periods are susceptible to PM-induced lung injury. For example, the increase in risk of death from long-term exposure to PM in six US cities has been shown to be in the area of 17% for the general population for a modest increase in total PM load of 24.5 micro-g/m3.

These studies will directly determine the consequences of a more peripheral site of aerosol deposition on the subsequent clearance of PM from the lung. It is well established that the negative health consequences of exposure to environmental PM increase as particle size is reduced. These studies will provide insight into how much of this effect is a consequence of the increased residence time of particles that are deposited more peripherally in the lungs. Such peripheral deposition occurs not only on the Lunar surface but here on Earth.

Task Progress & Bibliography Information FY2011 
Task Progress: Year 3 of this project has been largely stalled by the lack of flight availability, forcing us to re-order some activities and focus on ground studies in conjunction with Rui-Carlos Sa.

The major milestones achieved in this year are summarized as follows:

- Finalized the structural changes of flight hardware incorporating revisions arising from interim structural analyses.

- Performed a formal structural analysis of the equipment rack (requested by ESA/NASA). Rack shows positive margins in all aspects following modifications to lower the center of gravity (see appendices for images).

- Submitted an update Test Equipment Data Package reflecting the revised configuration of the system to NASA for pre-approval.

- Received formal radiation-use approval from JSC Radiation Safety group completing previous interim approval.

- In January used the flight system for collection of data in support of Rui-Carlos Sa's study at UNC on first 4 subjects. No issues identified. Note that these studies were moved ahead of flights in light of inability to secure flights.

- Performed end-to-end timeline tests of the flight timeline during January tests, confirming our ability to study 2 subjects per flight. This testing involved not only the inflight timeline, but the postflight timeline with the intersection with the following day's activities. Following minor adjustments in the timeline we are no confident of a 2-subject per day flight scenario with back to back flight days.

- Confirmed scientific comparability between Dicom (integrated) data and List Mode (real-time) data. This confirms our ability to acquire and use List Mode data inflight (our preferred approach). Note that Dicom data will still be acquired as well providing a degree of redundancy.

In addition to the activities listed above, we actively investigated the flight of the experiment on the ESA/Novespace A-300 Airbus flying from Bordeaux France. These attempts were ultimately unsuccessful but are included in the summary of attempts to fly this experiment and because they represented a considerable effort on our part.

Despite these considerable achievements we have been severely hampered by a lack of access to the reduced gravity aircraft.

In addition to these technical achievements, Dr. Rui-Carlos Pereira de Sá was awarded a NSBRI Post-Doctoral fellowship with Dr. G.K. Prisk as his mentor.

Abbreviated Statement of Status:

- CPHS/Radiation approval in place

- Subject certifications complete

- Hardware and procedures fully tested and functional

- Structural issues resolved (awaiting final approval)

- Ready for flight

- Waiting on flight manifesting

Bibliography Type: Description: (Last Updated: 03/11/2021)  Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Darquenne C, van Ertbruggen C, Prisk GK. "Convective flow dominates aerosol delivery to the lung segments." J Appl Physiol. 2011 Jul;111(1):48-54. http://dx.doi.org/10.1152/japplphysiol.00796.2010 ; PubMed PMID: 21474695 , Jul-2011
Articles in Peer-reviewed Journals Sá RC, Cronin MV, Henderson AC, Holverda S, Theilmann RJ, Arai TJ, Dubowitz DJ, Hopkins SR, Buxton RB, Prisk GK. "Vertical distribution of specific ventilation in normal supine humans measured by oxygen-enhanced proton MRI." J Appl Physiol. 2010 Dec;109(6):1950-9. Epub 2010 Oct 7. PMID: 20930129 http://dx.doi.org/10.1152/japplphysiol.00220.2010 , Dec-2010
Awards Prisk GK. "G.K. Prisk: Appointed Associate Editor Journal of Applied Physiology (effective 7/1/2011), April 2011." Apr-2011
Awards Bennett W. "William Bennett: Elected President International Society of Aerosols in Medicine (ISAM), January 2011." Jan-2011
Books/Book Chapters Prisk GK. "Gas exchange under altered gravitational stress." in "Comprehensive Physiology." Comprehensive Physiology, vol. 1/issue 1, p. 339-355, January 2011. Oxford, UK : Wiley-Blackwell, 2011. http://dx.doi.org/10.1002/cphy.c090007 , Jan-2011
Books/Book Chapters Prisk GK. "Microgravity." in "Comprehensive Physiology." Comprehensive Physiology vol. 1, issue 1, p. 485-497, 2011. Oxford, UK : Wiley-Blackwell, 2011. http://dx.doi.org/10.1002/cphy.c100014 , Jan-2011
Books/Book Chapters Prisk GK. "Pulmonary circulation in extreme environments." in "Comprehensive Physiology." Comprehensive Physiology vol. 1, issue 1, p. 319-338, 2011. Oxford, UK : Wiley-Blackwell, 2011. http://dx.doi.org/10.1002/cphy.c090006 , Jan-2011
Project Title:  Clearance of Particles Depositing in the Human Lung in Low Gravity Reduce
Fiscal Year: FY 2010 
Division: Human Research 
Research Discipline/Element:
HRP SHFH:Space Human Factors & Habitability (archival in 2017)
Start Date: 06/01/2008  
End Date: 05/31/2012  
Task Last Updated: 05/21/2010 
Download report in PDF pdf
Principal Investigator/Affiliation:   Prisk, G. Kim Ph.D., D.Sc. / University of California, San Diego 
Address:  Department of Medicine 
9500 Gilman Drive 
La Jolla , CA 92093-0852 
Email: kprisk@ucsd.edu 
Phone: 858-534-3233  
Congressional District: 53 
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of California, San Diego 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Bennett, William  University of North Carolina at Chapel Hill 
Darquenne, Chantal  University of California, San Diego 
Project Information: Grant/Contract No. NCC 9-58-HFP01604 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2007 Crew Health NNJ07ZSA002N 
Grant/Contract No.: NCC 9-58-HFP01604 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) SHFH:Space Human Factors & Habitability (archival in 2017)
Human Research Program Risks: (1) Dust:Risk of Adverse Health & Performance Effects of Celestial Dust Exposure (IRP Rev F)
(2) ExMC:Risk of Unacceptable Health and Mission Outcomes Due to Limitations of In-flight Medical Capabilities (IRP Rev E)
Human Research Program Gaps: (1) AEH Watch Item/NSBRI Research:What are the effects of lunar gravity on permissible exposure limits for inhalation of lunar dust? (Closed as of IRP Rev J)
(2) AEH02:What is the toxicity of lunar dust in the respiratory system? (Closed as of IRP Rev J)
(3) AEH05:What are the permissible exposure limits for inhalation of lunar dust? (Closed as of IRP Rev J)
(4) ExMC 4.26:We do not have the capability to screen for, diagnose, and treat disease due to dust exposure during exploration missions (IRP Rev E)
Task Description: Original Aims:

The deposition of particulate matter (PM) in the human lung is known to bring with it both long-term and short-term adverse health consequences. The deposition of particles in the lung is strongly influenced by gravitational sedimentation. Studies by our group have shown that normal gravity provides a screening effect whereby inhaled PM larger than 0.5 micron is mainly deposited in the larger airways where it is cleared by mucociliary clearance transport within ~one day. However in low-gravity, such as that on the surface of the Moon (~1/6G) and Mars (~3/8G), this protective 'gravitational screening' is less efficient, and as a result particles are deposited in the sensitive alveolar regions of the lung where residence times are very much longer. Further, there is evidence that the dust present on the surface of the Moon may possess potent toxicological properties. We hypothesize that clearance rates from the lung of particles deposited in low-gravity will be substantially reduced compared to that in 1G, resulting in increased residence times of these particles in the periphery of the lung, enhancing their potential to cause lung damage. In order to test this hypothesis we propose to measure the clearance rates (measured in 1G) over a few hours to ~1-2 days, of radio-labeled particles deposited in healthy humans both in 1G and in low-gravity corresponding to the lunar surface (~1/6G) during parabolic flight. These data will provide a comprehensive assessment of alterations in the clearance rate of particles inhaled under normal 1G conditions compared to particles inhaled under conditions of lunar gravity (1/6G). Such an assessment is needed to determine the degree of effort and cost required to control lunar dust within a planned lunar outpost.

Key Findings:

This second year of the project has focused on completing the technical aspects of the project and preparing for flight aboard the Reduced Gravity Aircraft. Much of this has been focused on obtaining the necessary approvals for flight (which proved to be much more challenging than we anticipated, despite us anticipating considerable challenges) and in flight scheduling (which as proved to be virtually impossible).

Our current status can be summarized as follows:

• CPHS/Radiation approval in place

• Subject certifications complete

• Hardware and procedures fully tested and functional

• Structural issues pending

• Ready for flight No Earlier Than July 19, 2010

• Waiting on flight manifesting

Year 3 Plan:

We hope to fly both the 4 micron particle size objective AND the 1 micron particle size objective in Year 3 of the project. As part of our Year 2 activities, and in response to the extreme difficulty experienced in scheduling reduced gravity flights, we devised and tested (on the ground) a 2-subject-per-flight experimental structure that will permit more efficient use of scarce reduced gravity flight opportunities.

Research Impact/Earth Benefits: Airborne particulate matter is a health hazard

The deposition of particulate matter (PM, often referred to as aerosols) in the human lung is known to bring with it both long-term and short-term adverse health consequences. On Earth, effects of PM-induced lung injury are most readily seen in individuals with pre-existing lung disease (i.e. asthma, chronic obstructive pulmonary disease). Studies suggest that particle-induced inflammation or edema likely enhance underlying pulmonary disease, leading to a worsening of already abnormal pulmonary ventilation/perfusion relationships and gas exchange. Such worsening can result in hypoxemia leading to fatal cardiac arrhythmia. There is also little question, that even healthy individuals exposed to PM for extended periods are susceptible to PM-induced lung injury. For example, the increase in risk of death from long-term exposure to PM in six US cities has been shown to be in the area of 17% for the general population for a modest increase in total PM load of 24.5 micrograms/m3.

These studies will directly determine the consequences of a more peripheral site of aerosol deposition on the subsequent clearance of PM from the lung. It is well-established that the negative health consequences of exposure to environmental PM increase as particle size is reduced. These studies will provide insight into how much of this effect is a consequence of the increased residence time of particles that are deposited more peripherally in the lungs. Such peripheral deposition occurs not only on the Lunar surface but here on Earth.

Task Progress & Bibliography Information FY2010 
Task Progress: Task Progress

Year 2 of this project has been focused on preparation for flight. The major milestones achieved in this year are summarized as follows:

• Received the gamma camera head from the manufacturer (MiE).

• Built the necessary structure to hold the camera head in place in the aircraft.

• Performed a detailed structural analysis on the gamma camera structure to satisfy the requirements for flight of the Reduced Gravity Office (RGO).

• Integrated the camera head into the structure and tested successfully.

• In conjunction with the manufacturer, performed hardware and software modifications of the gamma camera system permitting integrated acquisition of the scintillation data and the ancillary data (g-level, flow, subject position, and aerosol generation operation).

• Developed and successfully tested software to permit image reconstruction from raw gamma camera data permitting us to separate the gamma camera data on the basis of g-level or any other data of interest. Without this our in-flight acquisition would be limited by the integrated nature of the manufacture image capture software.

• Built and successfully tested the 4 micron aerosol generation hardware (piezo-electric aerosol generation) incorporating safety hardware for in-flight dosing of subjects with radioactive tracer.

• Built and successfully tested the 1 micron aerosol generation hardware (a fundamentally different hardware configuration from that above employing jet nebulization) incorporating safety hardware for in-flight dosing of subjects with radioactive tracer.

• Submitted a Test Equipment Data Package to RGO for "pre-approval".

• Received informal acceptance of the camera support structure.

• Successfully performed end-to-end testing of the experiment for flight using both 4 and 1 micron aerosols and incorporating a 2 subject per day timeline. This is a significant advance over our previously planned single subject operations, and will permit a more efficient use of precious reduced gravity flight opportunities.

• Performed all required medical examinations and physiological training of our subject population.

• Received NASA Committee on the Protection of Human Subjects (CPHS) approval in January 2010 (including NASA Radiation Safety approval) following initial submission in Feb 2009.

Despite these considerable achievements we have been severely hampered by a lack of access to the reduced gravity aircraft.

In addition to these technical achievements, Dr Rui-Carlos Pereira de Sá was awarded a NSBRI Post-Doctoral fellowship with Dr G.K. Prisk as his mentor.

Abbreviated Statement of Status:

• CPHS/Radiation approval in place

• Subject certifications complete

• Hardware and procedures fully tested and functional

• Structural issues pending

• Ready for flight No Earlier Than July 19, 2010

• Waiting on flight manifesting

Bibliography Type: Description: (Last Updated: 03/11/2021)  Show Cumulative Bibliography Listing
 
 None in FY 2010
Project Title:  Clearance of Particles Depositing in the Human Lung in Low Gravity Reduce
Fiscal Year: FY 2009 
Division: Human Research 
Research Discipline/Element:
HRP SHFH:Space Human Factors & Habitability (archival in 2017)
Start Date: 06/01/2008  
End Date: 05/31/2012  
Task Last Updated: 06/05/2009 
Download report in PDF pdf
Principal Investigator/Affiliation:   Prisk, G. Kim Ph.D., D.Sc. / University of California, San Diego 
Address:  Department of Medicine 
9500 Gilman Drive 
La Jolla , CA 92093-0852 
Email: kprisk@ucsd.edu 
Phone: 858-534-3233  
Congressional District: 53 
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of California, San Diego 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Bennett, William  University of North Carolina at Chapel Hill 
Darquenne, Chantal  University of California, San Diego 
Project Information: Grant/Contract No. NCC 9-58-HFP01604 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2007 Crew Health NNJ07ZSA002N 
Grant/Contract No.: NCC 9-58-HFP01604 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) SHFH:Space Human Factors & Habitability (archival in 2017)
Human Research Program Risks: (1) Dust:Risk of Adverse Health & Performance Effects of Celestial Dust Exposure (IRP Rev F)
(2) ExMC:Risk of Unacceptable Health and Mission Outcomes Due to Limitations of In-flight Medical Capabilities (IRP Rev E)
Human Research Program Gaps: (1) AEH Watch Item/NSBRI Research:What are the effects of lunar gravity on permissible exposure limits for inhalation of lunar dust? (Closed as of IRP Rev J)
(2) AEH02:What is the toxicity of lunar dust in the respiratory system? (Closed as of IRP Rev J)
(3) AEH05:What are the permissible exposure limits for inhalation of lunar dust? (Closed as of IRP Rev J)
(4) ExMC 4.26:We do not have the capability to screen for, diagnose, and treat disease due to dust exposure during exploration missions (IRP Rev E)
Task Description: Original Aims:

The deposition of particulate matter (PM) in the human lung is known to bring with it both long-term and short-term adverse health consequences. The deposition of particles in the lung is strongly influenced by gravitational sedimentation. Studies by our group have shown that normal gravity provides a screening effect whereby inhaled PM larger than 0.5 micron is mainly deposited in the larger airways where it is cleared by mucociliary clearance transport within ~one day. However in low-gravity, such as that on the surface of the Moon (~1/6G) and Mars (~3/8G), this protective 'gravitational screening' is less efficient, and as a result particles are deposited in the sensitive alveolar regions of the lung where residence times are very much longer. Further, there is evidence that the dust present on the surface of the Moon may possess potent toxicological properties. We hypothesize that clearance rates from the lung of particles deposited in low-gravity will be substantially reduced compared to that in 1G, resulting in increased residence times of these particles in the periphery of the lung, enhancing their potential to cause lung damage. In order to test this hypothesis we propose to measure the clearance rates (measured in 1G) over a few hours to ~1-2 days, of radio-labeled particles deposited in healthy humans both in 1G and in low-gravity corresponding to the lunar surface (~1/6G) during parabolic flight. These data will provide a comprehensive assessment of alterations in the clearance rate of particles inhaled under normal 1G conditions compared to particles inhaled under conditions of lunar gravity (1/6G). Such an assessment is needed to determine the degree of effort and cost required to control lunar dust within a planned lunar outpost.

Key Findings:

In this first year we have been exclusively engaged in technical work, and as such there are no scientific results yet available. In addition to the necessary technical accommodation work required to fly the gamma camera in the Reduced Gravity Aircraft, we have utilized existing flights (those funded by NSBRI under TD-00701) to verify the following technical objectives by flying small elements of hardware at no additional cost:

* Verified the functionality of two aerosol generation systems (on for each size range planned to be studied) under zero-gravity conditions. Both systems worked well.

* Measured the aerosol droplet size under flight conditions in the Reduced Gravity Aircraft to account for change in cabin pressure, g-level, and humidity. Verified only a minor influence of the flight environment compare to ground studies.

Impact of Recent Findings:

The ability of both aerosol generators to work adequately in reduced gravity, and the altered flight environment (especially reduced cabin pressure) is important. These tests verify aspect of our experiment design and confirm that control data to be collected on the ground will be directly comparable to those collected in flight.

Year 2 Plan:

By the completion of year 1 we expect to have largely fabricated the flight system. The beginning of year 2 will comprise ground-based tests of the actual flight system to verify functionality both in terms of standard function and in terms of usability in flight. These tests will occur at the University of North Carolina (Dr Bennett). Later in year 2 we plan the first flight studies using 4 micron particles (we will start with the larger particle size as this will provide the higher activity scans). Flight dates are currently subject to negotiation with NASA although we are hopeful of the first flights occurring in the second half for CY 2009.

Research Impact/Earth Benefits: Airborne particulate matter is a health hazard. The deposition of particulate matter (PM, often referred to as aerosols) in the human lung is known to bring with it both long-term and short-term adverse health consequences. On Earth, effects of PM-induced lung injury are most readily seen in individuals with pre-existing lung disease (i.e. asthma, chronic obstructive pulmonary disease). Studies suggest that particle-induced inflammation or edema likely enhance underlying pulmonary disease, leading to a worsening of already abnormal pulmonary ventilation/perfusion relationships and gas exchange. Such worsening can result in hypoxemia leading to fatal cardiac arrhythmia. There is also little question, that even healthy individuals exposed to PM for extended periods are susceptible to PM-induced lung injury. For example, the increase in risk of death from long-term exposure to PM in six US cities has been shown to be in the area of 17% for the general population for a modest increase in total PM load of 24.5 micro-g/m3.

These studies will directly determine the consequences of a more peripheral site of aerosol deposition on the subsequent clearance of PM from the lung. It is well-established that the negative health consequences of exposure to environmental PM increase as particle size is reduced. These studies will provide insight into how much of this effect is a consequence of the increased residence time of particles that are deposited more peripherally in the lungs. Such peripheral deposition occurs not only on the Lunar surface but here on Earth.

Task Progress & Bibliography Information FY2009 
Task Progress: Nearing the first year of this 4-year project, we have a list of completed technical milestones, all of which are important stepping stones to permit us to fly these challenging studies in the Reduced Gravity Aircraft. In this first year we have been exclusively engaged in technical work, and as such there are no scientific results yet available.

In this first year we have:

* Selected and ordered the gamma camera head from the manufacturer.

* Worked with the manufacturer to modify the computer system, making it suitable for parabolic flight.

* Obtained a non-functional gamma camera head from the manufacturer, to permit design of the structural accommodation.

* Designed the structural accommodation for the gamma camera head.

* Submitted the structural design to NASA for approval.

* Submitted the required documentation to the NASA Committee for the Protection of Human Subjects (CPHS).

* Submitted the required documentation to the NASA Radiation Safety and Use Committee.

* Verified the functionality of two aerosol generation systems (on for each size range planned to be studied) under zero-gravity conditions (hardware flown at no cost as part of other NSBRI-funded studies).

* Measured the aerosol droplet size under flight conditions in the Reduced Gravity Aircraft to account for change in cabin pressure, g-level, and humidity (hardware flown at no cost as part of other NSBRI-funded studies).

Bibliography Type: Description: (Last Updated: 03/11/2021)  Show Cumulative Bibliography Listing
 
Significant Media Coverage Burton A. "Research described in science article on the health hazards of lunar dust exposure in a major scientific publication. Title of article: Lunar lung disease." Environmental Health Perspectives. 2008 Oct;116(10):A423. PMID: 18941555, Oct-2008
Project Title:  Clearance of Particles Depositing in the Human Lung in Low Gravity Reduce
Fiscal Year: FY 2008 
Division: Human Research 
Research Discipline/Element:
HRP SHFH:Space Human Factors & Habitability (archival in 2017)
Start Date: 06/01/2008  
End Date: 05/31/2012  
Task Last Updated: 06/02/2008 
Download report in PDF pdf
Principal Investigator/Affiliation:   Prisk, G. Kim Ph.D., D.Sc. / University of California, San Diego 
Address:  Department of Medicine 
9500 Gilman Drive 
La Jolla , CA 92093-0852 
Email: kprisk@ucsd.edu 
Phone: 858-534-3233  
Congressional District: 53 
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of California, San Diego 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Bennett, William  University of N. Carolina at Chapel Hill 
Darquenne, Chantal   University of California, San Diego 
Project Information: Grant/Contract No. NCC 9-58-HFP01604 
Responsible Center: NSBRI 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2007 Crew Health NNJ07ZSA002N 
Grant/Contract No.: NCC 9-58-HFP01604 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) SHFH:Space Human Factors & Habitability (archival in 2017)
Human Research Program Risks: (1) Dust:Risk of Adverse Health & Performance Effects of Celestial Dust Exposure (IRP Rev F)
(2) ExMC:Risk of Unacceptable Health and Mission Outcomes Due to Limitations of In-flight Medical Capabilities (IRP Rev E)
Human Research Program Gaps: (1) AEH Watch Item/NSBRI Research:What are the effects of lunar gravity on permissible exposure limits for inhalation of lunar dust? (Closed as of IRP Rev J)
(2) AEH02:What is the toxicity of lunar dust in the respiratory system? (Closed as of IRP Rev J)
(3) AEH05:What are the permissible exposure limits for inhalation of lunar dust? (Closed as of IRP Rev J)
(4) ExMC 4.26:We do not have the capability to screen for, diagnose, and treat disease due to dust exposure during exploration missions (IRP Rev E)
Task Description: The deposition of particulate matter in the human lung is known to bring with it both long-term and short-term adverse health consequences. The deposition of particles in the lung is strongly influenced by gravitational sedimentation. Studies by this group have shown that normal gravity provides a screening effect whereby inhaled particulate matter larger than 0.5 micron is mainly deposited in the larger airways where it is cleared by mucociliary clearance transport within about one day. However, in low gravity, such as that on the surface of the moon (about 1/6 Earth's gravity) and Mars (about 3/8 of Earth's gravity), this protective 'gravitational screening' is less efficient, and as a result, particles are deposited in the sensitive alveolar regions of the lung where residence times are much longer. Further, there is evidence that the dust on the surface of the moon may possess potent toxicological properties.

We hypothesize that clearance rates from the lung of particles deposited in low gravity will be substantially reduced compared to that in normal gravity, resulting in increased residence times of these particles in the periphery of the lung, enhancing their potential to cause lung damage.

To test this hypothesis, we will measure the clearance rates (measured in normal gravity) over a few hours to about 1-2 days, of radio-labeled particles deposited in healthy humans both in normal and in low gravity corresponding to the lunar surface during parabolic flight. These data will provide a comprehensive assessment of alterations in the clearance rate of particles inhaled under normal gravity conditions compared to particles inhaled under conditions of lunar gravity. Such an assessment is needed to determine the degree of effort and cost required to control lunar dust within a planned lunar outpost.

Research Impact/Earth Benefits: 0

Task Progress & Bibliography Information FY2008 
Task Progress: New project for FY2008.

Bibliography Type: Description: (Last Updated: 03/11/2021)  Show Cumulative Bibliography Listing
 
 None in FY 2008