The Department of Veterans' Affairs Depleted Uranium Cohort in the Time of COVID-19: Translating a Traditional Surveillance Protocol to a Telehealth Platform.

OBJECTIVE: In 2021, 37 members of a cohort of depleted uranium-exposed Gulf War I veterans were evaluated using a protocol tailored to accommodate COVID-19 safety practices on a telehealth platform. METHODS: Individual elements of the legacy protocol were reviewed for urgency and feasibility of inclusion in a modified, telehealth platform. RESULTS: The redesigned protocol included a participant readiness for telehealth assessment, nurse and physician telehealth visits, collection of usual health questionnaires, and urine collections for exposure monitoring for uranium and other fragment-related metal measures. CONCLUSIONS: Despite some limitations in scope, the telehealth platform permitted a visual "visit" with surveillance participants who expressed a high comfort level with the format. The telehealth platform has apparent utility for occupational surveillance and should be explored as a standard approach for surveillance outside of public health emergencies.

Surveillance of Depleted Uranium-exposed Gulf War Veterans: More Evidence for Bone Effects.

ABSTRACT: Gulf War I veterans who were victims of depleted uranium (DU) "friendly-fire" incidents have undergone longitudinal health surveillance since 1994. During the spring of 2019, 36 members of the cohort were evaluated with a monitoring protocol including exposure assessment for total and isotopic uranium concentrations in urine and a comprehensive review of health outcomes, including measures of bone metabolism and bone mineral density (BMD) determination. Elevated urine U concentrations were observed in cohort members with retained depleted uranium (DU) shrapnel fragments. In addition, a measure of bone resorption, N-telopeptide, showed a statistically significant increase in those in the high DU subgroup, a finding consistent with a statistically significant decrease in bone mass also observed in this high DU subgroup compared to the low DU subgroup. After more than 25 y since first exposure to DU, an aging cohort of military veterans continues to show few U-related health effects in known target organs of U toxicity. The new finding of impaired BMD in the high DU subgroup has now been detected in two consecutive surveillance visits. While this is a biologically plausible uranium effect, it is not reflected in other measures of bone metabolism in the full cohort, which have largely been within normal limits. However, ongoing accrual of the U burden from fragment absorption over time and the effect of aging further impairing BMD suggest the need for future surveillance assessments of this cohort.

Surveillance results and bone effects in the Gulf War depleted uranium-exposed cohort.

A small group of Gulf War I veterans wounded in depleted uranium (DU) friendly-fire incidents have been monitored in a clinical surveillance program since 1993. During the spring of 2017, 42 members of the cohort were evaluated with a protocol which includes exposure monitoring for total and isotopic uranium concentrations in urine and a comprehensive assessment of health outcomes including measures of bone metabolism, and for participants >50 years, bone mineral density (BMD) determination. Elevated urine U concentrations were observed in cohort members with retained DU shrapnel fragments. Only the mean serum estradiol concentration, a marker of bone metabolism, was found to be significantly different for lower-vs- higher urine U (uU) cohort sub-groups. For the first time, a significant deficit in BMD was observed in the over age 50, high uU sub-group. After more than 25 years since first exposure to DU, an aging cohort of military veterans continues to exhibit few U-related adverse health effects in known target organs of U toxicity. The new finding of reduced BMD in older cohort members, while biologically plausible, was not suggested by other measures of bone metabolism in the full (all ages) cohort, as these were predominantly within normal limits over time. Only estradiol was recently found to display a difference as a function of uU grouping. As BMD is further impacted by aging and the U-burden from fragment absorption accrues in this cohort, a U effect may be clarified in future surveillance visits.

Impulse oscillometry measurement of distal airways obstruction in depleted uranium-exposed Gulf War veterans.

INTRODUCTION: A cohort of Gulf War I veterans who sustained exposure to depleted uranium undergoes biennial surveillance for potential uranium-related health effects. We performed impulse oscillometry and hypothesized that veterans with higher uranium body burdens would have more obstructive abnormalities than those with lower burdens. METHODS: We compared pulmonary function of veterans in high versus low urine uranium groups by evaluating spirometry and oscillometry values. RESULTS: Overall mean spirometry and oscillometry resistance values fell within the normal ranges. There were no significant differences between the high and low uranium groups for any parameters. However, more veterans were classified as having obstruction by oscillometry (42%) than spirometry (8%). CONCLUSIONS: While oscillometry identified more veterans as obstructed, obstruction was not uranium-related. However, the added sensitivity of this method implies a benefit in wider surveillance of exposed cohorts and holds promise in identifying abnormalities in areas of the lung historically described as silent.

The U.S. Department of Veterans' Affairs depleted uranium exposed cohort at 25 Years: Longitudinal surveillance results.

BACKGROUND: A small group of Gulf War I veterans wounded in depleted uranium (DU) friendly-fire incidents have been monitored for health changes in a clinical surveillance program at the Veterans Affairs Medical Center, Baltimore since 1994. METHODS: During the spring of 2015, an in-patient clinical surveillance protocol was performed on 36 members of the cohort, including exposure monitoring for total and isotopic uranium concentrations in urine and a comprehensive assessment of health outcomes. RESULTS: On-going mobilization of U from embedded fragments is evidenced by elevated urine U concentrations. The DU isotopic signature is observed principally in participants possessing embedded fragments. Those with only an inhalation exposure have lower urine U concentration and a natural isotopic signature. CONCLUSIONS: At 25 years since first exposure to DU, an aging cohort of military veterans continues to show no U-related health effects in known target organs of U toxicity. As U body burden continues to accrue from in-situ mobilization from metal fragment depots, and increases with exposure duration, critical tissue-specific U concentration thresholds may be reached, thus recommending on-going surveillance of this veteran cohort.

Biologic monitoring and surveillance results for the department of veterans affairs' depleted uranium cohort: Lessons learned from sustained exposure over two decades.

BACKGROUND: A small group of Gulf War I veterans wounded in depleted uranium (DU) friendly fire incidents have been monitored in a clinical surveillance program at the Veterans Affairs Medical Center, Baltimore since 1994. METHODS: An in-patient clinical surveillance protocol was performed on 35 members of the cohort, including exposure monitoring for total and isotopic uranium concentrations in urine and a comprehensive assessment of health outcomes. RESULTS: Although urine U concentrations continue to be elevated in this group, illustrating on-going in situ mobilization of U from embedded fragments, no consistent U-related health effects have been observed. CONCLUSIONS: Now more than 20 years since first exposure to DU, an aging cohort of military veterans continues to show no U-related health effects in known target organs of U toxicity. As tissue concentrations continue to accrue with exposure duration, critical tissue-specific U concentration thresholds may be reached, thus recommending on-going surveillance of this veteran cohort.

Long-term exposure to depleted uranium in Gulf-War veterans does not induce chromosome aberrations in peripheral blood lymphocytes.

Depleted uranium (DU) is a high-density heavy metal that has been used in munitions since the 1991 Gulf War. DU is weakly radioactive and chemically toxic, and long-term exposure may cause adverse health effects. This study evaluates genotoxic effects of exposure to DU by measuring chromosome damage in peripheral blood lymphocytes with fluorescence in situ hybridization whole-chromosome painting. Study participants are Gulf War-I Veterans with embedded DU fragments and/or inhalation exposure due to involvement in friendly-fire incidents; they are enrolled in a long-term health surveillance program at the Baltimore Veterans Administration Medical Center. Blood was drawn from 35 exposed male veterans aged 39 to 62 years. Chromosomes 1, 2, and 4 were painted red and chromosomes 3, 5, and 6 were simultaneously labeled green. At least 1800 metaphase cells per subject were scored. Univariate regression analyses were performed to evaluate the effects of log(urine uranium), age at time of blood draw, log(lifetime X-rays), pack-years smoked and alcohol use, against frequencies of cells with translocated chromosomes, dicentrics, acentric fragments, color junctions and abnormal cells. No significant relationships were observed between any cytogenetic endpoint and log(urine uranium) levels, smoking, or log(lifetime X-rays). Age at the time of blood draw showed significant relationships with all endpoints except for cells with acentric fragments. Translocation frequencies in these Veterans were all well within the normal range of published values for healthy control subjects from around the world. These results indicate that chronic exposure to DU does not induce significant levels of chromosome damage in these Veterans.

Pulmonary health effects in Gulf War I service members exposed to depleted uranium.

OBJECTIVE: In a population of Gulf War I veterans who sustained inhalational exposure to depleted uranium during friendly fire incidents in 1991, we evaluated whether those with high body burdens of uranium were more likely to have pulmonary health abnormalities than those with low body burdens. METHODS: We compared self-reported respiratory symptoms, mean pulmonary function values, and prevalence of low-dose chest computed tomography abnormalities between high and low urine uranium groups. RESULTS: We found no significant differences in respiratory symptoms, abnormal pulmonary function values, or prevalence of chest computed tomography abnormalities between high and low urine uranium groups. Overall, the cohort's pulmonary function values fell within the expected clinical range. CONCLUSIONS: Our results support previous estimates that the depleted uranium levels inhaled during the 1991 friendly fire incidents likely do not cause long-term adverse pulmonary health effects.

The Gulf War depleted uranium cohort at 20 years: bioassay results and novel approaches to fragment surveillance.

During the 1991 GulfWar, U.S. service members were exposed to depleted uranium (DU) through friendly-fire incidents involving DU munitions and vehicles protected by DU armor. Routes of exposure to DU involved inhalation of soluble and insoluble DU oxide particles, wound contamination, and retained embedded DU metal fragments that continue to oxidize in situ and release DU to the systemic circulation. A biennial health surveillance program established for this group of Veterans by the U.S. Department of Veterans Affairs has shown continuously elevated urine DU concentrations in the subset of veterans with embedded fragments for over 20 years. While the 2011 assessment was comprehensive, few clinically significant U-related health effects were observed. This report is focused on health outcomes associated with two primary target organs of concern for long term effects of this combat-related exposure to DU. Renal biomarkers showed minimal DU-related effects on proximal tubule function and cytotoxicity, but significant biomarker results were observed when urine concentrations of multiple metals also found in fragments were examined together. Pulmonary tests and questionnaire results indicate that pulmonary function after 20 y remains within the clinical normal range. Imaging of DU embedded fragment-associated tissue for signs of inflammatory or proliferative reactions possibly associated with foreign body transformation or with local alpha emissions from DU was also conducted using PET-CT and ultrasound. These imaging tools may be helpful in guiding decisions regarding removal of fragments.

Measures of genotoxicity in Gulf war I veterans exposed to depleted uranium.

Exposure to depleted uranium (DU), an alpha-emitting heavy metal, has prompted the inclusion of markers of genotoxicity in the long-term medical surveillance of a cohort of DU-exposed Gulf War veterans followed since 1994. Using urine U (uU) concentration as the measure of U body burden, the cohort has been stratified into low-u (<0.10 µg U/g creatinine) and high-u groups (≥ 0.10 µg U/g creatinine). Surveillance outcomes for this cohort have historically included markers of mutagenicity and clastogenicity, with past results showing generally nonsignificant differences between low- vs. high-U groups. However, mean hypoxanthine-guanine phosphoribosyl transferase (HPRT) mutant frequencies (MFs) have been almost 50% higher in the high-U group. We report here results of a more comprehensive protocol performed in a 2009 evaluation of a subgroup (N = 35) of this cohort. Four biomarkers of genotoxicity [micronuclei (MN), chromosome aberrations, and MFs of HPRT and PIGA] were examined. There were no statistically significant differences in any outcome measure when results were compared between the low- vs. high-U groups. However, modeling of the HPRT MF results suggests a possible threshold effect for MFs occurring in the highest U exposed cohort members. Mutational spectral analysis of HPRT mutations is underway to clarify a potential clonal vs. a threshold uU effect to explain this observation. This study provides a comprehensive evaluation of a human population chronically exposed to DU and demonstrates a relatively weak genotoxic effect of the DU exposure. These results may explain the lack of clear epidemiologic evidence for U carcinogenicity in humans. Environ. Mol. Mutagen., 2011. © 2011 Wiley-Liss, Inc.

Biological monitoring and surveillance results of Gulf War I veterans exposed to depleted uranium.

OBJECTIVE: To relate medical surveillance outcomes to uranium biomonitoring results in a group of depleted uranium (DU)-exposed, Gulf War I veterans. METHODS: Thirty-two veterans of Gulf War I who were victims of 'friendly fire' involving DU weapons, in whom exposure assessment can accurately be measured, had urine uranium concentrations determined using ICP-MS technology. Clinical laboratory parameters were measured and related to urine uranium concentrations. Data were examined by stratifying the cohort into a low U group, <0.10 mug/g creatinine versus a high U group, >/=0.10 mug/g creatinine and assessing differences between groups. RESULTS: Over a decade after first exposure, soldiers possessing embedded DU fragments continue to excrete elevated concentrations of uranium in urine. No clinically significant uranium related health effects were observed in blood count, blood chemistries including renal markers, neuropsychological measures, and semen quality or genotoxicity measures. Markers of early changes in renal glomerular and tubular function were not statistically different between groups; however, genotoxicity measures continue to show subtle, mixed results. CONCLUSION: Persistent urine uranium elevations continue to be observed more than 12 years since first exposure. Despite this, renal and other clinical abnormalities were not observed, likely due to the 'relatively' low uranium burden in this cohort compared to historical uranium-exposed occupational groups. Continuing surveillance is indicated, however, due to the on-going nature of the exposure. These results are an important finding in light of the on-going controversy regarding health effects observed in soldiers of the Gulf War and other conflicts, whose uranium exposure assessment is unable to be accurately determined.

Health effects of depleted uranium on exposed Gulf War veterans: a 10-year follow-up.

Medical surveillance of a group of U.S. Gulf War veterans who were victims of depleted uranium (DU) "friendly fire" has been carried out since the early 1990s. Findings to date reveal a persistent elevation of urine uranium, more than 10 yr after exposure, in those veterans with retained shrapnel fragments. The excretion is presumably from ongoing mobilization of DU from fragments oxidizing in situ. Other clinical outcomes related to urine uranium measures have revealed few abnormalities. Renal function is normal despite the kidney's expected involvement as the "critical" target organ of uranium toxicity. Subtle perturbations in some proximal tubular parameters may suggest early although not clinically significant effects of uranium exposure. A mixed picture of genotoxic outcomes is also observed, including an association of hypoxanthine-guanine phosphoribosyl transferase (HPRT) mutation frequency with high urine uranium levels. Findings observed in this chronically exposed cohort offer guidance for predicting future health effects in other potentially exposed populations and provide helpful data for hazard communication for future deployed personnel.