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Pierson, Duane

Publications and source records attributed to Pierson, Duane.

At least 19 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS2019

Stress Induced Immune Dysregulation: A Continuum Spanning Antarctica Winterover, Spaceflight, and Terrestrial Patients

Spaceflight is a unique environment characterized by stress, microgravity, isolation, circadian misalignment, and radiation exposure and impacts immune health. Planned long duration missions to Mars are a top priority for NASA and mitigating the negative health consequences of spaceflight is particularly important. Terrestrial analogs are a vital aspect of spaceflight research since data from astronauts is limited and it is costly to receive samples from ISS. The most relevant ground analog would include station lifestyle, stress, disrupted circadian rhythms and isolation. This analysis compares various aspects of immune dysregulation in astronauts during long-duration orbital spaceflight to groundanalogs. Astronaut data were also compared to a clinical immunodeficiency population, shingles patients, to help interpret clinical risks during deep space missions. A comprehensive evaluation was performed across hypoxic interior Antarctica, normoxic coastal Antarctica, HERA, and astronauts which included plasma and mitogen stimulated cytokine profiles, T-cell function, and peripheral leukocyte distribution. A cross platform analysis was then performed to define in-flight immune alterations, determine analog appropriateness, and interpret clinical risk.

Krieger, Stephanie↗
NASA NTRS2016

Evidence Report: Risk of Adverse Health Effects Due to Host-Microorganism Interactions

While preventive measures limit the presence of many medically significant microorganisms during spaceflight missions, microbial infection of crewmembers cannot be completely prevented. Spaceflight experiments over the past 50 years have demonstrated a unique microbial response to spaceflight culture, although the mechanisms behind those responses and their operational relevance were unclear. In 2007, the operational importance of these microbial responses was emphasized as the results of an experiment aboard STS-115 demonstrated that the enteric pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) increased in virulence in a murine model of infection. The experiment was reproduced in 2008 aboard STS-123 confirming this finding. In response to these findings, the Institute of Medicine of the National Academies recommended that NASA investigate this risk and its potential impact on the health of the crew during spaceflight. NASA assigned this risk to the Human Research Program. To better understand this risk, evidence has been collected and reported from both spaceflight analog systems and actual spaceflight including Mir, Space Shuttle, and ISS missions. Although the performance of virulence studies during spaceflight are challenging and often impractical, additional information has been and continues to be collected to better understand the risk to crew health. Still, the uncertainty concerning the extent and severity of these alterations in host-microorganism interactions is very large and requires more investigation as the focus of human spaceflight shifts to longer-duration exploration class missions.

Ott, C. Mark↗
NASA NTRS2016

Risk of Adverse Health Effects Due to Host-Microorganism Interactions

Numerous spaceflight experiments have been conducted to investigate alterations in microbial responses resulting from culture during spaceflight and spaceflight-analogs. However, recent studies investigating spaceflight-associated alterations in microbial virulence have initiated the review and production of evidence to better understand the impact these alterations would have on the incidence of infectious disease during a spaceflight exploration mission. The preponderance of evidence indicates that alterations in microbial gene expression and phenotype (including virulence) are occurring; however, the clinical implications of such changes are still unclear. Greater knowledge is required including a better understanding of the mechanism behind unique spaceflight-associated microbial responses to determine how this environmental stimulus impacts various microorganisms, their diversity and concentration in the spacecraft and crew microbiome, their impact on the vehicle and crew, and their resistance to current mitigation and antibiotic regimens. This knowledge will enable us to determine requirements, guidelines, and processes for design and monitoring of the next generation vehicles.

Ott, C. Mark↗
NASA NTRS2015

Determination of Roles of Microgravity and Ionizing Radiation on the Reactivation of Epstein-Barr Virus In Vitro

Astronauts experience symptomatic and asymptomatic herpes virus reactivation during spaceflight. We have shown increases in reactivation of Epstein-Barr virus (EBV), cytomegalovirus (CMV) and varicella zoster virus (VZV) and shedding in body fluids (saliva and urine) in astronauts during space travel. Alterations in immunity, increased stress hormone levels, microgravity, increased radiation, and other conditions unique to spaceflight may promote reactivation of latent herpes viruses. Unique mechanico-physico forces associated with spaceflight can have profound effects on cellular function, especially immune cells. In space flight analog studies such as Antarctica, bed rest studies, and NASA's undersea habitat (Aquarius), reactivation of these viruses occurred, but to a lesser extent than spaceflight. Spaceflight analogs model some spaceflight factors, but none of the analogs recreates all factors experienced in space. Most notably, microgravity and radiation are not included in many analogs. Stress, processed through the HPA axis and SAM systems, induces viral reactivation. However, the respective roles of microgravity and increased space radiation levels or if any synergy exists are not known. Therefore, we studied the effect of modeled space radiation and/or microgravity, independent of the immune system on the changes in cellular gene expression that results in viral (EBV) reactivation. The effects of modeled microgravity and low shear on EBV replication and cellular and EBV gene expression were studied in human B-lymphocyte cell cultures. Latently infected B-lymphocytes were propagated in the rotating wall bioreactor and irradiated with the various dosages of gamma irradiation. At specific time intervals following exposure to modeled microgravity, the cells and supernatant were harvested and reactivation of EBV were assessed by measuring EBV and gene expression, DNA methylation, and infectious virus production.

Mehta, Satish K↗
NASA NTRS2015

Risk of Adverse Health Effects Due to Host-Microorganism Interactions

While preventive measures limit the presence of many medically significant microorganisms during spaceflight missions, microbial infection of crewmembers cannot be completely prevented. Spaceflight experiments over the past 50 years have demonstrated a unique microbial response to spaceflight culture, although the mechanisms behind those responses and their operational relevance were unclear. In 2007, the operational importance of these microbial responses was emphasized as the results of an experiment aboard STS-115 demonstrated that the enteric pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) increased in virulence in a murine model of infection. The experiment was reproduced in 2008 aboard STS-123 confirming this finding. In response to these findings, the Institute of Medicine of the National Academies recommended that NASA investigate this risk and its potential impact on the health of the crew during spaceflight. NASA assigned this risk to the Human Research Program. To better understand this risk, evidence has been collected and reported from both spaceflight analog systems and actual spaceflight. Although the performance of virulence studies during spaceflight are challenging and often impractical, additional information has been and continues to be collected to better understand the risk to crew health. Still, the uncertainty concerning the extent and severity of these alterations in host-microorganism interactions is very large and requires more investigation.

Ott, C. Mark↗
NASA NTRS2014

Rapid Electrochemical Detection and Identification of Microbiological and Chemical Contaminants for Manned Spaceflight Project

Microbial control in the spacecraft environment is a daunting task, especially in the presence of human crew members. Currently, assessing the potential crew health risk associated with a microbial contamination event requires return of representative environmental samples that are analyzed in a ground-based laboratory. It is therefore not currently possible to quickly identify microbes during spaceflight. This project addresses the unmet need for spaceflight-compatible microbial identification technology. The electrochemical detection and identification platform is expected to provide a sensitive, specific, and rapid sample-to-answer capability for in-flight microbial monitoring that can distinguish between related microorganisms (pathogens and non-pathogens) as well as chemical contaminants. This will dramatically enhance our ability to monitor the spacecraft environment and the health risk to the crew. Further, the project is expected to eliminate the need for sample return while significantly reducing crew time required for detection of multiple targets. Initial work will focus on the optimization of bacterial detection and identification. The platform is designed to release nucleic acids (DNA and RNA) from microorganisms without the use of harmful chemicals. Bacterial DNA or RNA is captured by bacteria-specific probe molecules that are bound to a microelectrode, and that capture event can generate a small change in the electrical current (Lam, et al. 2012. Anal. Chem. 84(1): 21-5.). This current is measured, and a determination is made whether a given microbe is present in the sample analyzed. Chemical detection can be accomplished by directly applying a sample to the microelectrode and measuring the resulting current change. This rapid microbial and chemical detection device is designed to be a low-cost, low-power platform anticipated to be operated independently of an external power source, characteristics optimal for manned spaceflight and areas where power and computing resources are scarce.

Pierson, Duane↗
NASA NTRS2014

Microbiology and Crew Medical Events on the International Space Station

The closed environment of the International Space Station (ISS) creates an ideal environment for microbial growth. Previous studies have identified the ubiquitous nature of microorganisms throughout the space station environment. To ensure safety of the crew, microbial monitoring of air and surface within ISS began in December 2000 and continues to be monitored on a quarterly basis. Water monitoring began in 2009 when the potable water dispenser was installed on ISS. However, it is unknown if high microbial counts are associated with inflight medical events. The microbial counts are determined for the air, surface, and water samples collected during flight operations and samples are returned to the Microbiology laboratory at the Johnson Space Center for identification. Instances of microbial counts above the established microbial limit requirements were noted and compared inflight medical events (any non-injury event such as illness, rashes, etc.) that were reported during the same calendar-quarter. Data were analyzed using repeated measures logistic regression for the forty-one US astronauts flew on ISS between 2000 and 2012. In that time frame, instances of microbial counts being above established limits were found for 10 times for air samples, 22 times for surface samples and twice for water. Seventy-eight inflight medical events were reported among the astronauts. A three times greater risk of a medical event was found when microbial samples were found to be high (OR = 3.01; p =.007). Engineering controls, crew training, and strict microbial limits have been established to mitigate the crew medical events and environmental risks. Due to the timing issues of sampling and the samples return to earth, identification of particular microorganisms causing a particular inflight medical event is difficult. Further analyses are underway.

Oubre, Cherie↗
NASA NTRS2014

Microbiology and Crew Medical Events on the International Space Station

The closed environment of the International Space Station (ISS) creates an ideal environment for microbial growth. Previous studies have identified the ubiquitous nature of microorganisms throughout the space station environment. To ensure safety of the crew, microbial monitoring of air and surface within ISS began in December 2000 and continues to be monitored on a quarterly basis. Water monitoring began in 2009 when the potable water dispenser was installed on ISS. However, it is unknown if high microbial counts are associated with inflight medical events. The microbial counts are determined for the air, surface, and water samples collected during flight operations and samples are returned to the Microbiology laboratory at the Johnson Space Center for identification. Instances of microbial counts above the established microbial limit requirements were noted and compared inflight medical events (any non-injury event such as illness, rashes, etc.) that were reported during the same calendar-quarter. Data were analyzed using repeated measures logistic regression for the forty-one US astronauts flew on ISS between 2000 and 2012. In that time frame, instances of microbial counts being above established limits were found for 10 times for air samples, 22 times for surface samples and twice for water. Seventy-eight inflight medical events were reported among the astronauts. A three times greater risk of a medical event was found when microbial samples were found to be high (OR = 3.01; p =.007). Engineering controls, crew training, and strict microbial limits have been established to mitigate the crew medical events and environmental risks. Due to the timing issues of sampling and the samples return to earth, identification of particular microorganisms causing a particular inflight medical event is difficult. Further analyses are underway.

Oubre, Cherie M.↗
NASA NTRS2013

Rapid Detection of Herpes Viruses for Clinical Applications

There are eight herpes viruses that infect humans, causing a wide range of diseases resulting in considerable morbidity and associated costs. Varicella zoster virus (VZV) is a human herpes virus that causes chickenpox in children and shingles in adults. Approximately 1,000,000 new cases of shingles occur each year; post-herpetic neuralgia (PHN) follows shingles in 100,000 to 200,000 people annually. PHN is characterized by debilitating, nearly unbearable pain for weeks, months, and even years. The onset of shingles is characterized by pain, followed by the zoster rash, leading to blisters and severe pain. The problem is that in the early stages, shingles can be difficult to diagnose; chickenpox in adults can be equally difficult to diagnose. As a result, both diseases can be misdiagnosed (false positive/negative). A molecular assay has been adapted for use in diagnosing VZV diseases. The polymerase chain reaction (PCR) assay is a non-invasive, rapid, sensitive, and highly specific method for VZV DNA detection. It provides unequivocal results and can effectively end misdiagnoses. This is an approximately two-hour assay that allows unequivocal diagnosis and rapid antiviral drug intervention. It has been demonstrated that rapid intervention can prevent full development of the disease, resulting in reduced likelihood of PHN. The technology was extended to shingles patients and demonstrated that VZV is shed in saliva and blood of all shingles patients. The amount of VZV in saliva parallels the medical outcome.

Pierson, Duane↗
NASA NTRS2013

Plasma Cytokine Concentrations Indicate In-vivo Hormonal Regulation of Immunity is Altered During Long-Duration Spaceflight

Background: Aspects of immune system dysregulation associated with long‐duration spaceflight have yet to be fully characterized, and may represent a clinical risk to crewmembers during deep space missions. Plasma cytokine concentration may serve as an indicator of in vivo physiological changes or immune system mobilization. Methods: The plasma concentrations of 22 cytokines were monitored in 28 astronauts during long‐duration spaceflight onboard the International Space Station. Blood samples were collected three times before flight, 3‐5 times during flight (depending on mission duration), at landing and 30 days post‐landing. Analysis was performed by bead array immunoassay. Results: With few exceptions, minimal detectable mean plasma levels (<10 pg/ml) were observed at baseline (launch minus 180) for innate inflammatory cytokines or adaptive regulatory cytokines, however IL‐1ra and several chemokines were constitutively present. An increase in the plasma concentration IL‐8, IL‐1ra, Tpo, CCL4, CXCL5, TNF(alpha), GM‐CSF and VEGF was observed associated with spaceflight. Significant post‐flight increases were observed for IL‐6 and CCL2. No significant alterations were observed during or following spaceflight for adaptive/T‐regulatory cytokines (IL‐2, IFN(gamma), IL‐17, IL4, IL‐5, IL‐10). Conclusions: This pattern of cytokine dysregulation suggests multiple physiological adaptations persist during flight, including inflammation, leukocyte recruitment, angiogenesis and thrombocyte regulation.

Crician, Brian E.↗
NASA NTRS2010

Immune System Dysregulation, Viral Reactivation and Stress During Short-Duration Space Flight

This slide presentation reviews a study that was conducted to ascertain if the immune system dysregulation, viral reactivation and stress from short duration space flight were a result of the stress of landing and readjustment to gravity. The objectives of the study were to replace several recent immune studies with one comprehensive study that will include in-flight sampling; address lack of in-flight data: (i.e., determine the in-flight status of immunity, physiological stress, viral immunity/reactivation); determine the clinical risk related to immune dysregulation for exploration class spaceflight; and determine the appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures.

Crucian, Brian↗
NASA NTRS2010

Validation of Procedures for Monitoring Crewmember Immune Function

The objective of this Supplemental Medical Objective (SMO) is to determine the status of the immune system, physiological stress and latent viral reactivation (a clinical outcome that can be measured) during both short and long-duration spaceflight. In addition, this study will develop and validate an immune monitoring strategy consistent with operational flight requirements and constraints. Pre-mission, in-flight and post-flight blood and saliva samples will be obtained from participating crewmembers. Assays included peripheral immunophenotype, T cell function, cytokine profiles, viral-specific immunity, latent viral reactivation (EBV, CMV, VZV), and stress hormone measurements. To date, 18 short duration (now completed) and 8 long-duration crewmembers have completed the study. The long-duration phase of this study is ongoing. For this presentation, the final data set for the short duration subjects will be discussed.

Pierson, Duane↗
NASA NTRS2010

CHOICE - Directed Study: Consequences of longterm- Confinement and Hypobaric HypOxia on Immunity in the Antarctic Concordia Environment

Concerning ground-based space physiological research, the choice of analog must carefully match the system of interest. For spaceflight-associated immune dysregulation (SAID), Antarctica winter-over has emerged as potentially the best terrestrial analog. The prolonged mission durations, extreme/dangerous environment, station-based lifestyle, isolation from outside world, disrupted circadian rhythms, and other psychological aspects make this analog extremely high fidelity for exploration-class space missions (long duration lunar, Mars). NASA, ESA and RSA are currently investigating SAID, with NASA currently operating the Integrated Immune flight study. It is desirable to have a ground analog for SAID validated, so that potential countermeasures might be validated terrestrially prior to during flight. For this presentation, NASA data collected on the winterover 2009 crewmembers, baseline through early deployment will be presented. Through early deployment (approximately 2-3 weeks at Concordia), phenotypic alterations included increased levels of memory T cells, shifts among the CD8+ T cell compartment to a more mature phenotype, and increases in constitutively activated T cells. CD8+/IFNg+ T cell percentages, and T cell blastogenesis functional responses were depressed early deployment as compared to healthy controls. In four compatible subjects, secreted T cell Th1/Th2 cytokines were measured following culture stimulation, and a Th2 shift was observed as compared to controls. Post-winter over frozen sample return will be required to determine if this shift persisted during the winter over period. Additionally, circadian rhythms remained altered compared to baseline, as determined through 5x daily cortisol measurements. Latent viral reactivation will not be determined until frozen sample return occurs.

Sams, Clarence↗
NASA NTRS2010

Integrated Immune

This slide presentation reviews the program to replace several recent studies about astronaut immune systems with one comprehensive study that will include in-flight sampling. The study will address lack of in-flight data to determine the inflight status of immune systems, physiological stress, viral immunity, to determine the clinical risk related to immune dysregulation for exploration class spaceflight, and to determine the appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures.

Crucian, Brian↗