Respiratory Health Associated with Systemic Metal Exposure in Post 9/11 Veterans in the Department of Veterans Affairs Toxic Embedded Fragment Registry.

OBJECTIVE: Adverse respiratory outcomes in post-9/11 Veterans with elevated urinary metal measures and enrolled in the VA's Toxic Embedded Fragment registry were compared to those without elevated urinary metals. METHODS: Veterans completed questionnaires, pulmonary physiology tests (pulmonary function and oscillometry) and provided urine samples for analysis of 13 metals. Respiratory symptoms, diagnoses and physiology measures were compared in Veterans with ≥1 urine metal elevation to those without metal elevations, adjusted for covariates, including smoking. RESULTS: Among 402 study participants, 24% had elevated urine metals, often just exceeding upper limits of reference values. Compared to Veterans without elevated metals, those with elevated metals had had higher FEV1 values but similar frequencies of respiratory symptoms and diagnoses and abnormalities on pulmonary physiology tests. CONCLUSIONS: Mild systemic metal elevations in post 9/11 Veterans are not associated with adverse respiratory health outcomes.

Succimer chelation does not produce lasting reductions of blood lead levels in a rodent model of retained lead fragments.

Retained lead fragments from nonfatal firearm injuries pose a risk of lead poisoning. While chelation is well-established as a lead poisoning treatment, it remains unclear whether chelation mobilizes lead from embedded lead fragments. Here, we tested whether 1) DMSA/succimer or CaNa2EDTA increases mobilization of lead from fragments in vitro, and 2) succimer is efficacious in chelating fragment lead in vivo, using stable lead isotope tracer methods in a rodent model of embedded fragments. DMSA was > 10-times more effective than CaNa2EDTA in mobilizing fragment lead in vitro. In the rodent model, succimer chelation on day 1 produced the greatest blood lead reductions, and fragment lead was not mobilized into blood. However, with continued chelation and over 3-weeks post-chelation, blood lead levels rebounded with mobilization of lead from the fragments. These findings suggest prolonged chelation will increase fragment lead mobilization post-chelation, supporting the need for long-term surveillance in patients with retained fragments.

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.

Laying the Foundation for a Mesothelioma Patient Registry: Development of Data Collection Tools.

Mesothelioma, a cancer of mesothelial cells that line the chest, lungs, heart, and abdomen, is a relatively rare disease. In the United States, approximately 3000 individuals are diagnosed with mesothelioma annually. The primary risk factor for mesothelioma is occupational asbestos exposure which can occur decades prior to disease development, though in approximately 20% of cases, known asbestos exposure is lacking. While several other countries have developed mesothelioma registries to collect key clinical and exposure data elements to allow better estimation of incidence, prevalence, and risk factors associated with disease development, no national mesothelioma registry exists in the U.S. Therefore, as part of a larger feasibility study, a patient exposure questionnaire and a clinical data collection tool were created using a series of key informant interviews. Findings suggest that risk factor and clinical data collection via an on-line questionnaire is feasible, but specific concerns related to confidentiality, in the context of employer responsibility for exposure in the unique U.S. legal environment, and timing of enrollment must be addressed. Lessons learned from piloting these tools will inform the design and implementation of a mesothelioma registry of national scope.

Self-reported respiratory outcomes associated with blast exposure in post 9/11 veterans.

BACKGROUND: Blast lung overpressure has received interest as a cause of chronic respiratory disease in Service members who deployed in support of U.S. military operations in Southwest Asia and Afghanistan since 2001. We studied whether veterans who experienced blast exposure report more chronic respiratory symptoms and diagnoses compared to deployed veterans who did not. METHODS: 9,000 veterans included in the Department of Veterans Affairs Toxic Embedded Fragment Registry were invited to complete a survey assessing chronic respiratory symptoms, diagnoses, and exposures. Blast exposure was assessed using the Brief Traumatic Brain Injury Screen and by presence of other symptoms such as blast-induced loss of consciousness. RESULTS: Participants (n = 2147) were predominantly <40 years old, served in the Army, and injured on average 12.8 years previously. 91% reported blast exposure. Blast-exposed veterans were significantly more likely to report cough (OR 1.8), wheeze (OR 2.4), and dyspnea (OR 1.8), even after adjustment for covariates including smoking and occupational exposures to dust, fume, and gas. Veterans reporting higher severity of blast impact, such as traumatic brain injury or loss of consciousness, were more likely to report cough, wheeze, or dyspnea. Veterans with higher severity of blast impact by multiple measures were also more likely to report having COPD. Those reporting a physician-diagnosis of traumatic brain injury were significantly more likely to report having both asthma (OR 1.5) and COPD (OR 1.5). CONCLUSIONS: Blast exposure is associated with respiratory symptoms and COPD. Respiratory system evaluation may warrant inclusion as a standard part of barotrauma health assessment.

Characteristics Associated With Health Care Worker Knowledge and Confidence in Elastomeric Half-Mask Respirator Use.

OBJECTIVE: This study evaluated health care workers' (HCWs') knowledge and confidence in using elastomeric half-mask respirator (EHMR) attributes known to influence usage. METHODS: Health care workers were surveyed regarding their EHMR donning and doffing experience. Respondents were categorized into competency categories based on their scores. Category differences were analyzed using χ 2 and multiple logistic regression. RESULTS: Seventy-two percent showed high levels of EHMR donning and doffing knowledge and confidence (mastery); however, 21% had greater confidence than knowledge (misinformed). Respiratory therapists had greater odds of mastery than other HCWs ( P < 0.05), whereas those working in medical/surgical and pediatric units had greater odds of doubt than other HCWs ( P < 0.01). CONCLUSIONS: Although most HCWs show high knowledge and confidence with EHMR use, strategies to confirm respirator use competency may ensure greater HCWs protection.

Respiratory Protection Perceptions among Malian Health Workers: Insights from the Health Belief Model.

Reusable respiratory protective devices called elastomeric respirators have demonstrated their effectiveness and acceptability in well-resourced healthcare settings. Using standard qualitative research methods, we explored the feasibility of elastomeric respirator use in low- and middle-income countries (LMIC). We conducted interviews and focus groups with a convenience sample of health workers at one clinical center in Mali. Participants were users of elastomeric and/or traditional N95 respirators, their supervisors, and program leaders. Interview transcripts of participants were analyzed using a priori constructs from the Health Belief Model (HBM) and a previous study about healthcare respirator use. In addition to HBM constructs, the team identified two additional constructs impacting uptake of respirator use (system-level factors and cultural factors). Together, these framed the perceptions of Malian health workers and highlighted both facilitators of and barriers to respirator use uptake. As needs for respiratory protection from airborne infectious hazards become more commonly recognized, elastomeric respirators may be a sustainable and economic solution for health worker protection in LMIC.

Physiological Impacts of Surgical Mask Coverage of Elastomeric Half-mask Respirator Exhalation Valves in Healthcare Workers.

OBJECTIVES: Elastomeric half-mask respirator (EHMR) use in healthcare increased significantly during the COVID-19 pandemic. Concern for potential release of infectious aerosols from EHMR exhalation valves prompted recommendations to cover them with surgical masks (SMs), thereby improving source control. The physiological and subjective effects of wearing a SM over the exhalation valve of an EHMR, however, are unknown. METHODS: Twelve healthy healthcare worker volunteers completed a 30-min series of simulated healthcare-related tasks, including resting, talking, walking, and bending, proning and supinating a weighted manikin, and performing cardiopulmonary resuscitation. This series recurred three times with different mask configurations-SM only, EHMR only, or EHMR with SM covering the exhalation valve. A transcutaneous sensor continuously measured carbon dioxide (tcPCO2), oxygen saturation (SpO2), and heart rate (HR) from each subject. Subjects scored their rates of perceived exertion (RPE) and levels of discomfort after each round. Physiological parameters and subjective scores were analyzed using mixed linear models with a fixed effect for mask type, activity, age, body mass index (BMI), and gender. Analysis also tested for interaction between mask type and activity. RESULTS: Physiological parameters remained within normal ranges for all mask configurations but varied by task. Statistically significant but small decreases in mean tcPCO2 (37.17 versus 37.88 mmHg, P < 0.001) and SpO2 (97.74 versus 97.94%, P < 0.001) were associated with wearing EHMR with SM over the exhalation valve compared with EHMR alone. Mean HR did not differ between these mask configurations. Wearing SM only was associated with lower RPE and level of discomfort compared with EHMR, but these subjective scores did not differ when comparing EHMR with SM to EHMR only. Age, BMI, and gender had no significant effect on any outcomes. CONCLUSIONS: Wearing a SM over an EHMR did not produce clinically significant changes in tcPCO2, SpO2, or HR compared with uncovered EHMR during healthcare-related tasks. Covered EHMR use also did not affect perceived exertion or discomfort compared with uncovered EHMR use. Covering the exhalation valve of an EHMR with a SM for source control purposes can be done safely.

Urine miRNAs as potential biomarkers for systemic reactions induced by exposure to embedded metal.

Aim: Explore the potential of urine microRNAs as biomarkers that may reflect the biological responses to pure metals embedded in skeletal muscle over time. Materials & methods: We tested a panel of military-relevant metals embedded in the gastrocnemius muscles of 3-month-old, male, Sprague-Dawley rats (n = 8/group) for a duration of 1, 3, 6 and 12 months, and performed small RNA-sequencing on the urine samples. Results: Results provide potential tissue targets affected by metal exposure and a list of unique or common urine microRNA biomarkers indicative of exposure to various metals, highlighting a complex systemic response. Conclusion: We have identified a panel of miRNAs as potential urine biomarkers to reflect the complex systemic response to embedded metal exposure.

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.

The Utility of Spot vs 24-Hour Urine Samples for Metal Determination in Veterans With Retained Fragments.

OBJECTIVES: The objective of this investigation is to explore the utility of using a spot urine sample in lieu of a 24-hour collection in assessing fragment-related metal exposure in war-injured veterans. METHODS: Twenty-four veterans collected each urine void over a 24-hour period in separate containers. Concentrations of 13 metals were measured in each void and in a pooled 24-hour sample using inductively coupled plasma mass spectrometry. To assess the reliability of spot sample measures over time, intraclass correlations (ICCs) were calculated across all spot samples. Lin's concordance correlation coefficient was used to assess agreement between a randomly selected spot urine sample and each corresponding 24-hour sample. RESULTS: In total, 149 spot urine samples were collected. Ten of the 13 metals measured had ICCs more than 0.4, suggesting "fair to good" reliability. Concordance coefficients were more than 0.4 for all metals, suggesting "moderate" agreement between spot and 24-hour concentrations, and more than 0.6 for seven of the 13 metals, suggesting "good" agreement. CONCLUSIONS: Our fair to good reliability findings, for most metals investigated, and moderate to good agreement findings for all metals, across the range of concentrations observed here, suggest the utility of spot urine samples to obtain valid estimates of exposure in the longitudinal surveillance of metal-exposed populations.

Self-reported impact of respirator use on health care worker ability to perform patient care.

In a study of 1,152 health care workers surveyed prior to the COVID-19 pandemic, most disagreed that respiratory protective equipment use interferes with patient care but reported that it would affect respirator use compliance if it did. A patient's fear reaction variably influenced self-reported health care worker compliance with respirator use. Strategies to improve protective equipment design may remove potential barriers to respirator use and allow better health care worker-patient relationships.

The management of embedded metal fragment patients and the role of chelation Therapy: A workshop of the Department of Veterans Affairs-Walter Reed National Medical Center.

Exposure to retained metal fragments from war-related injuries can result in increased systemic metal concentrations, thereby posing potential health risks to target organs far from the site of injury. Given the large number of veterans who have retained fragments and the lack of clear guidance on how to medically manage these individuals, the Department of Veterans Affairs (VA) convened a meeting of chelation experts and clinicians who care for embedded fragment patients to discuss current practices and provide medical management guidance. Based on this group's clinical expertise and review of published literature, the evidence presented suggests that, at least in the case of lead fragments, short-term chelation therapy may be beneficial for embedded fragment patients experiencing acute symptoms associated with metal toxicity; however, in the absence of clinical symptoms or significantly elevated blood lead concentrations (greater than 80 µg/dL), chelation therapy may offer little to no benefit for individuals with retained fragments and pose greater risks due to remobilization of metals stored in bone and other soft tissues. The combination of periodic biomonitoring to assess metal body burden, longitudinal fragment imaging, and selective fragment removal when metal concentrations approach critical injury thresholds offers a more conservative management approach to caring for patients with embedded fragments.

Semen Uranium Concentrations in Depleted Uranium Exposed Gulf War Veterans: Correlations with Other Body Fluid Matrices.

Environmental metal exposure, as well as dietary metals, may adversely affect semen quality even as others play an essential role in normal spermatogenesis and fertility. Measures of seminal fluid metals have therefore been of high interest in the last several decades but have shown inconsistent results in correlations with some semen quality parameters. As well, environmental metal measures across various body fluid matrices have not been consistently correlated contrary to what one might hypothesize based on a systemic body burden of metal. This may be due to the body fluid matrices assessed and to other differences in laboratory methods and sample preparation. Measures of uranium, a potentially toxic metal in humans, have not previously been reported in the semen of environmentally metal-exposed populations. We report here uranium seminal fluid results and the high correlation of uranium concentrations across several body fluid matrices in a cohort of military veterans exposed to depleted uranium in combat events during the Iraqi Gulf War. These results inform the risk communication conversation for exposed populations and broaden the public health assessments from various exposure scenarios.

Simultaneous Determination of Uranium and Depleted Uranium Isotopic Ratio Using Inductively Coupled Mass Spectrometry.

We have developed and validated a method for the simultaneous quantitative measurement of total uranium (TU) and uranium 235 U/238 U isotopic ratio (UIR) in urine by inductively coupled plasma mass spectrometry (ICP-MS) using a Thermo Scientific iCAP-Q instrument. The performance characteristics of the assay were determined to be in compliance with clinical laboratory standards. The assay was linear in the concentration range of 1.0 to 500.0 ng/liter TU. The method was precise and accurate with limits of detection of 2.5 ng/liter for TU and 9.8 ng/liter for UIR. The accuracy was >93% and the coefficient of variation (% CV) was <5.0% for both TU and UIR. All results were within established guidelines and agreed-upon criteria, and the results fell within the certified range for the reference controls. The method has thus been shown to be effective as a simple, precise, and sensitive analytical technique for testing urine samples. © 2018 by John Wiley & Sons, Inc.