Stella E. Hines

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

AbstractDuring 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.

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.

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 cohorts 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.

Update on flavoring-induced lung disease.

Purpose of review Since the initial report of bronchiolitis obliterans in microwave popcorn workers, exposures to flavoring substances have been identified in a variety of food and flavor manufacturing facilities and in the consumer market. Attempts to decrease the risk of lung disease have included the use of flavoring substitutes; however, these chemicals may cause similar injury. This article reviews recent flavoring exposures and data on the pathogenesis, clinical characteristics, and surveillance of flavoring-induced lung disease. Recent findings Diacetyl and 2,3-pentanedione exposures have occurred in food production facilities that make cookies, cereal, chocolate, and coffee. Airborne levels often exceed proposed occupational exposure limits. Cases of biopsy-proven bronchiolitis obliterans in heavy popcorn consumers have also been reported. New data demonstrate the presence of diacetyl and 2,3-pentanedione in flavored nicotine liquids used in electronic nicotine delivery systems. Summary Diacetyl substitutes cause similar peri-bronchiolar fibrotic lesions in animal studies. Their use may continue to place workers at risk for flavoring-induced lung disease, which may present in forms beyond that of fixed airflow obstruction, contributing to delays in identifying and treating patients with flavoring-induced lung disease. Engineering controls, medical surveillance and personal protective equipment can limit flavorings exposure and risk for lung disease.

The role of lymphocyte proliferation tests in assessing occupational sensitization and disease.

Purpose of reviewLymphocyte proliferation testing (LPT) is used in diagnosing occupationally acquired delayed-type hypersensitivity. It has been used in beryllium-health effects, and its role is expanding in metal allergy. It may find application in diagnosis of other sensitizers. Recent findingsUse of the beryllium LPT (BeLPT) in medical surveillance identifies beryllium sensitization at low exposure with chronic beryllium disease (CBD) that leads to physiologic impairment and need for immunosuppressive medications. New studies indicate that both beryllium exposure and genetic variation are associated with increased risk of CBD. Borderline positive BeLPTs warrant inclusion into diagnostic algorithms. Furthermore, use of LPTs to diagnose metal allergy is being proposed in diagnosis of chromium allergy and hypersensitivity to surgical implants. New occupational sensitizers continue to be identified including metalworking fluids, the sterilizing agent ortho-phthalaldehyde and the solvent para-chlorobenzotrifluoride. Use of LPT in occupational surveillance to these agents and other known sensitizers may play expanding roles. SummaryLymphocyte proliferation testing serves a valuable role in diagnosing occupational sensitization, as demonstrated with beryllium-health effects, as cases continue to be found at low exposure levels. The use of LPTs in diagnosing contact allergy is expanding, and new applications may be identified in human and animal studies.

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. HighlightsGulf War I veterans wounded with depleted uranium are monitored for health changes.In 2015 in‐patient clinical surveillance was performed on 36 members of the cohort.Mobilization of U from embedded fragments is evidenced by elevated U in urine.This cohort of continues to show no U‐related health effects.

Evaluation of the patient with an exposure-related disease: the occupational and environmental history.

Purpose of review Although the process of taking an occupational and environmental history has remained largely the same, the context in which it is done has changed dramatically over recent years. This review examines the role of the occupational and environmental history in the context of the changing nature of medical practice and discusses methods for evaluating patients with contemporary exposure-related respiratory illnesses. Recent findings Surveillance for occupational lung disease using mnemonic devices, screening questions and the use of structured questionnaires can significantly increase the likelihood and accuracy of detection. Electronic health records likewise can be adapted to include the most important elements of the occupational and environmental history. Summary The emergence of new technologies and industries will lead to respiratory diseases in novel occupational and environmental contexts. Using the methods described herein can make detecting these diseases easier and less time-consuming.

Recommendations for a Clinical Decision Support System for Work-Related Asthma in Primary Care Settings

Objective: The aim of this study was to describe a recommended clinical decision support (CDS) approach for work-related asthma for incorporation in electronic health records (EHRs) for primary care health care providers. Methods: Subject matter experts convened by the American Thoracic Society reviewed available guidelines and published literature to develop specific recommendations. Results: It is important to recognize possible work-related asthma among persons with new-onset or worsening asthma. The work group recommends incorporating three simple questions about temporal relations between asthma symptoms and work in EHR systems and identified specific clinical conditions to trigger this intervention. Patients with positive responses to the three questions should have the asthma diagnosis documented and have further evaluation, education, and possible referral. Conclusion: An effective CDS system for improving recognition of work-related asthma may help reduce morbidity and mortality of asthma in adults.

Forty years of reference values for respiratory system impedance in adults: 1977–2017

OBJECTIVE To provide an evidence-based review of published data regarding normal range reference values and prediction equations for measurements of respiratory impedance using forced oscillation technique (FOT) and impulse oscillometry (IOs) in adults. METHODS A non-language-restricted search was performed using forced oscillation technique and impulse oscillometry as primary terms. Original research studies reporting respiratory system impedance reference values or prediction equations based on cohorts of ≥100 healthy adults were included. Publications cited in identified studies were also considered for inclusion. RESULTS Of 882 publications identified, 34 studies were included: 14 studies of FOT, 19 studies of IOs, and one study of both techniques. Nineteen studies provided prediction equations. Most reports were from Europe (n = 20) and Asia (n = 12) and included relatively small cohorts (median = 264 subjects). Across publications, there was marked variability in performance and technique of impedance measurements. Height and sex emerged as major contributors to available prediction equations. The contribution of weight was more pronounced at the obese end of the weight spectrum. The contribution of age was less clear, and elderly were largely under-represented. Ethnicity likely plays a role, but was under-reported in currently available literature. Inclusion of current and former smokers in some studies further confound the results. CONCLUSIONS Currently available literature providing reference values and prediction equations for respiratory impedance measurements in adults is limited. Until larger-scale standardized studies are available, the choice of prediction equations should be based on datasets that best represent the target patient population and modality in use within each pulmonary physiology laboratory.

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.