Beryllium disease among construction trade workers at Department of Energy nuclear sites: A follow-up.

BACKGROUND: Construction workers at U.S. Department of Energy (DOE) nuclear weapons facilities are screened to identify DOE-related occupational illnesses, including beryllium sensitization (BeS) and chronic beryllium disease (CBD). The study objectives were to estimate beryllium disease risks and the CBD claims acceptance rate in the energy workers' benefits program. METHODS: Workers diagnosed with BeS via beryllium lymphocyte proliferation test (BeLPT) included in screening examinations were interviewed about subsequent diagnosis of CBD. We estimated the proportion who developed CBD based on the ratio of CBD cases, based on self-reported compensation claim status, to all workers with BeS interviewed. We used stratified analyses to explore trends in disease frequency by age, race, sex, DOE employment duration, site, trade group, and cigarette smoking history. RESULTS: Between 1998 and 2020, 21,854 workers received a BeLPT; 262 (1.20%) had BeS (two abnormals or one abnormal plus one borderline test); 212 (0.97%) had a single abnormal BeLPT. Of 177 BeS workers interviewed, 35 (19.8%) reported an accepted CBD compensation claim. The claims acceptance rate among BeS workers increased with years of DOE employment, from 8.4% with <5 years to 33.3% for >25 or more years. Five of 68 interviewed workers with a single positive BeLPT reported CBD claim acceptance; an additional CBD case was confirmed by chart review (8.8%). CONCLUSIONS: Years of DOE work predict the risk of developing CBD among those sensitized and getting a claim for CBD accepted. Ongoing surveillance and increased awareness of the risk of beryllium exposure and CBD as an occupational disease among construction workers are needed.

HLA-DPB1 E69 genotype and exposure in beryllium sensitisation and disease.

OBJECTIVES: Human leukocyte antigen-DP beta 1 (HLA-DPB1) with a glutamic acid at the 69th position of the ß chain (E69) genotype and inhalational beryllium exposure individually contribute to risk of chronic beryllium disease (CBD) and beryllium sensitisation (BeS) in exposed individuals. This retrospective nested case-control study assessed the contribution of genetics and exposure in the development of BeS and CBD. METHODS: Workers with BeS (n=444), CBD (n=449) and beryllium-exposed controls (n=890) were enrolled from studies conducted at nuclear weapons and primary beryllium manufacturing facilities. Lifetime-average beryllium exposure estimates were based on workers' job questionnaires and historical and industrial hygienist exposure estimates, blinded to genotype and case status. Genotyping was performed using sequence-specific primer-PCR. Logistic regression models were developed allowing for over-dispersion, adjusting for workforce, race, sex and ethnicity. RESULTS: Having no E69 alleles was associated with lower odds of both CBD and BeS; every additional E69 allele increased odds for CBD and BeS. Increasing exposure was associated with lower odds of BeS. CBD was not associated with exposure as compared to controls, yet the per cent of individuals with CBD versus BeS increased with increasing exposure. No evidence of a gene-by-exposure interaction was found for CBD or BeS. CONCLUSIONS: Risk of CBD increases with E69 allele frequency and increasing exposure, although no gene by environment interaction was found. A decreased risk of BeS with increasing exposure and lack of exposure response in CBD cases may be due to the limitations of reconstructed exposure estimates. Although reducing exposure may not prevent BeS, it may reduce CBD and the associated health effects, especially in those carrying E69 alleles.

[Management of occupational health for adverse health effects of beryllium and its compounds in workplaces - Recent trends and issues in Japan].

OBJECTIVES: Beryllium is primarily used in its metallic form, in alloys, or in beryllium oxide ceramics. Its physical and mechanical properties make it useful for many applications across a range of industries. Because beryllium is recognized as a sensitizing and carcinogenic agent, the management of occupational health for workers who may be occupationally exposed to beryllium has long been an important issue in the world. Under these circumstances, the U.S. Occupational Safety and Health Administration (OSHA) had published a rule in January 2017, to prevent the development of chronic beryllium disease and lung cancer. This rule strengthens the regulations governing the use of beryllium and its compounds. With the announcement of the OSHA rule in January 2017, the purpose of this study is to gain insight into the health problems and industrial hygiene associated with the use of beryllium and share the issues related to the management of occupational health for persons working with beryllium in Japan. METHODS: We collected information regarding the beryllium industry, beryllium exposure, beryllium-induced health disorders, OSHA rule of January 2017, and regulations for beryllium use in Japan. After reviewing them, we discussed the issues concerning occupational health management of workers exposed to beryllium in Japan. RESULTS: It has been reconfirmed that in recent years, the most serious health problem due to beryllium exposure is chronic beryllium disease caused by beryllium sensitization. Management of occupational health that emphasizes reduction of beryllium sensitization and early detection of beryllium-sensitized workers is important. CONCLUSIONS: It was suggested that the following should be considered as the issues of management of occupational health of workers exposed to beryllium in Japan: (1) Collect epidemiologic data on health hazards from beryllium exposure in Japan. (2) Review the diagnostic items of special medical check-ups. (3) Review the definition of beryllium and its compounds in the Ordinance on Prevention of Hazards due to Specified Chemical Substances.

Transplantation for work-related lung disease in the USA.

OBJECTIVES: Work-related lung diseases (WRLDs) are entirely preventable. To assess the impact of WRLDs on the US transplant system, we identified adult lung transplant recipients with a WRLD diagnosis specified at the time of transplant to describe demographic, payer and clinical characteristics of these patients and to assess post-transplant survival. METHODS: Using US registry data from 1991 to 2018, we identified lung transplant recipients with WRLDs including coal workers' pneumoconiosis, silicosis, asbestosis, metal pneumoconiosis and berylliosis. RESULTS: The frequency of WRLD-associated transplants has increased over time. Among 230 lung transplants for WRLD, a majority were performed since 2009; 79 were for coal workers' pneumoconiosis and 78 were for silicosis. Patients with coal workers' pneumoconiosis were predominantly from West Virginia (n=31), Kentucky (n=23) or Virginia (n=10). States with the highest number of patients with silicosis transplant were Pennsylvania (n=12) and West Virginia (n=8). Patients with metal pneumoconiosis and asbestosis had the lowest and highest mean age at transplant (48.8 and 62.1 years). Median post-transplant survival was 8.2 years for patients with asbestosis, 6.6 years for coal workers' pneumoconiosis and 7.8 years for silicosis. Risk of death among patients with silicosis, coal workers' pneumoconiosis and asbestosis did not differ when compared with patients with idiopathic pulmonary fibrosis. CONCLUSIONS: Lung transplants for WRLDs are increasingly common, indicating a need for primary prevention and surveillance in high-risk occupations. Collection of patient occupational history by the registry could enhance case identification and inform prevention strategies.

[Diagnostic difficulties of chronic pulmonary berylliosis in France]. / Difficultés diagnostiques de la bérylliose pulmonaire chronique en France.

INTRODUCTION: The epidemiology of chronic beryllium disease (CBD) in France is poorly understood. The aim of this study was to determine the number of prevalent cases of CBD in France between 2010 and 2014. METHODS: We conducted a national survey using a specific questionnaire distributed by the professional pathology services. RESULTS: In total, 33 CBD cases were reported in France, with a diagnosis established between 1982 and 2014. 85% (28/33) of CBD cases resulted from professional exposure and mostly concerned foundry workers (39%). A definite diagnosis defined by the association of an abnormal beryllium lymphocyte proliferation test and of a granulomatous inflammatory response in the lung, was obtained in 29/33 cases (88%). The other cases were probable CBD, defined by a granulomatous lung disease with a beryllium exposure, but without evidence of beryllium sensitisation. The diagnosis of granulomatous disease was confirmed a mean of 4 years after the end of exposure. The median delay between diagnosis of a granulomatous disease and diagnosis of CBD was 2 years (range 0-38 years). A genetic predisposition was found in 14 of 17 tested patients (82%). CONCLUSION: In this study, we report 33 cases of CBD followed in France between 2010 and 2014. The poor understanding of CBD and the exposure leading to it, the late development after the end of exposure, the complexity of the diagnosis and the similarities with sarcoidosis may explain the small number of cases reported.

Associations of Metrics of Peak Inhalation Exposure and Skin Exposure Indices With Beryllium Sensitization at a Beryllium Manufacturing Facility.

OBJECTIVES: Peak beryllium inhalation exposures and exposure to the skin may be relevant for developing beryllium sensitization (BeS). The objective of this study was to identify risk factors associated with BeS to inform the prevention of sensitization, and the development of chronic beryllium disease (CBD). METHODS: In a survey of short-term workers employed at a primary beryllium manufacturing facility between the years 1994-1999, 264 participants completed a questionnaire and were tested for BeS. A range of qualitative and quantitative peak inhalation metrics and skin exposure indices were created using: personal full-shift beryllium exposure measurements, 15 min to 24 h process-specific task and area exposure measurements, glove measurements as indicator of skin exposure, process-upset information gleaned from historical reports, and self-reported information on exposure events. Hierarchical clustering was conducted to systematically group participants based on similarity of patterns of 16 exposure variables. The associations of the exposure metrics with BeS and self-reported skin symptoms (in work areas processing beryllium salts as well as in other work areas) were evaluated using correlation analysis, log-binomial and logistic regression models with splines. RESULTS: Metrics of peak inhalation exposure, indices of skin exposure, and using material containing beryllium salts were significantly associated with skin symptoms and BeS; skin symptoms were a strong predictor of BeS. However, in this cohort, we could not tease apart the independent effects of skin exposure from inhalation exposure, as these exposures occurred simultaneously and were highly correlated. Hierarchical clustering identified groups of participants with unique patterns of exposure characteristics resulting in different prevalence of BeS and skin symptoms. A cluster with high skin exposure index and use of material containing beryllium salts had the highest prevalence of BeS and self-reported skin symptoms, followed by a cluster with high inhalation and skin exposure index and a very small fraction of jobs in which beryllium salts were used. A cluster with low inhalation and skin exposure and no workers using beryllium salts had no cases of BeS. CONCLUSION: Multiple pathways and types of exposure were associated with BeS and may be important for informing BeS prevention. Prevention efforts should focus on controlling airborne beryllium exposures with attention to peaks, use of process characteristics (e.g. the likelihood of upset conditions to design interventions) minimize skin exposure to beryllium particles, and in particular, eliminate skin contact with beryllium salts to interrupt potential exposure pathways for BeS risk.

A mortality study of beryllium workers.

We aimed at investigating mortality among beryllium-exposed workers, according to solubility of beryllium and beryllium compounds. We conducted an historical cohort study of 16,115 workers employed during 1925-2008 in 15 facilities, including eight entailing exposure to insoluble beryllium and seven entailing exposure to soluble/mixed beryllium compounds, who were followed up for mortality until 2011. Data were analyzed using indirect standardization and Cox regression modeling. Lung cancer standardized mortality ratio (SMR, national reference rates) was 1.02 (95% confidence interval [CI]: 0.94-1.10) in the whole cohort, 0.88 (95% CI: 0.75-1.03) in the insoluble beryllium subcohort, and 1.09 (95% CI: 0.99-1.09) in the soluble/mixed beryllium subcohort. For lung cancer, there was an association with period of hire in soluble/mixed beryllium plants but not in insoluble plants, and, conversely, employment in soluble/mixed plants was associated with increased mortality only among workers hired before 1955. There was no trend with duration of employment. Mortality from chronic beryllium disease increased, in particular, among workers hired before 1955 in soluble/mixed beryllium facilities. There was no increase in lung cancer mortality in the entire cohort and lung cancer mortality was not increased among beryllium workers hired in 1955 or later in soluble/mixed beryllium facilities, or at any time among those employed in insoluble beryllium facilities.

Harriet Hardy and the workers of Los Alamos: a campus-community historical investigation.

Harriet Hardy, protégé of Alice Hamilton, spent 1948 in the Health Division of Los Alamos Scientific Laboratory. The contemporary campaign for federal legislation to compensate nuclear workers brought to the fore living retirees in whose cases of occupational illness Hardy had a role in diagnosis or case management. A third case is documented in archival records. Methods of participatory action research were used to better document the cases and strategize in light of the evidence, thereby assisting the workers with compensation claims. Medical and neuropsychological exams of the mercury case were conducted. Hardy's diary entries and memoirs were interpreted in light of medicolegal documentation and workers' recollections. Through these participatory research activities, Harriet Hardy's role and influence both inside and outside the atomic weapons complex have been elucidated. An important lesson learned is the ongoing need for a system of protective medical evaluations for nuclear workers with complex chemical exposures.

Illness absences among beryllium sensitized workers.

OBJECTIVES: This study examined absence rates among US Department of Energy workers who had beryllium sensitization (BeS) or were diagnosed with chronic beryllium disease (CBD) compared with those of other workers. METHODS: We used the lymphocyte proliferation test to determine beryllium sensitivity. In addition, we applied multivariable logistic regression to compare absences from 2002 to 2011 between workers with BeS or CBD to those without, and survival analysis to compare time to first absence by beryllium sensitization status. Finally, we examined beryllium status by occupational group. Results. Fewer than 3% of the 19,305 workers were BeS, and workers with BeS or CBD had more total absences (odds ratio [OR] = 1.31; 95% confidence interval [CI] = 1.18, 1.46) and respiratory absences (OR = 1.51; 95% CI = 1.24, 1.84) than did other workers. Time to first absence for all causes and for respiratory conditions occurred earlier for workers with BeS or CBD than for other workers. Line operators and crafts personnel were at increased risk for BeS or CBD. Conclusions. Although not considered "diseased," workers with BeS have higher absenteeism compared with nonsensitized workers.

Exposure factors associated with chronic beryllium disease development in Beryllium BioBank participants.

OBJECTIVE: To assess the importance of occupational history for beryllium-exposed workers. METHODS: Beryllium BioBank data were analyzed for 532 subjects in the following three groups: beryllium-exposed, beryllium-sensitized, and chronic beryllium disease. Predictor variables were several questionnaire-derived exposure indices. RESULTS: Cumulative exposure estimated from a standardized interview contributes to differentiating beryllium-exposed from chronic beryllium disease. The likelihood of progression from sensitization to disease was associated with peak-level weighted exposure hours. CONCLUSIONS: Selecting workers for extensive diagnostic testing should consider each worker's duration and characteristics of exposure. The intensity and total hours of exposure should be evaluated rather than relying on only the total years.

Unsuspected exposure to beryllium: potential implications for sarcoidosis diagnoses.

Exposure to Beryllium (Be) can cause sensitization (BeS) and chronic beryllium disease (CBD) in some individuals.  Even relatively low exposures may be sufficient to generate an asymptomatic, or in some cases a symptomatic, immune response. Since the clinical presentation of CBD is similar to that of sarcoidosis, it is helpful to have information on exposure to beryllium in order to reduce misdiagnosis. The purpose of this pilot study is to explore the occurrence of Be surface deposits at worksites with little or no previous reported use of commercially available Be products.  The workplaces chosen for this study represent a convenience sample of businesses in eastern Iowa. One hundred thirty-six surface dust samples were collected from 27 businesses for analysis of Be. The results were then divided into categories by the amount of detected Be according to U.S. Department of Energy guidelines as described in 10 CFR 850.30 and 10 CFR 850.31. Overall, at least one of the samples at 78% of the work sites tested contained deposited Be above the analytical limit of quantitation (0.035 µg beryllium per sample).  Beryllium was detected in 46% of the samples collected. Twelve percent of the samples exceeded 0.2 µg/100 cm² and 4% of the samples exceeded a Be concentration of 3 µg/100 cm². The findings from this study suggest that there may be a wider range and greater number of work environments that have the potential for Be exposure than has been documented previously.  These findings could have implications for the accurate diagnosis of sarcoidosis.

A novel alternative to environmental monitoring to detect workers at risk for beryllium exposure-related health effects.

The purpose of this study was to describe a methodology for surveillance and monitoring of beryllium exposure using biological monitoring to complement environmental monitoring. Eighty-three Israeli dental technicians (mean age 41.6 ± 1.36 years) and 80 American nuclear machining workers (54.9 ± 1.21 years) were enrolled. Biological monitoring was carried out by analyzing particle size (laser technique) and shape (image analysis) in 131/163 (80.3%) induced sputum samples (Dipa Analyser, Donner Tech, Or Aquiva, Israel). Environmental monitoring was carried out only in the United States (Sioutas impactor, SKC, Inc., Eighty Four, Pa.). Pulmonary function testing performance and induced sputum retrieval were done by conventional methods. Sixty-three Israeli workers and 37 American workers were followed up for at least 2 years. Biological monitoring by induced sputum indicated that a >92% accumulation of <5 µm particles correlated significantly to a positive beryllium lymphocyte proliferation test result (OR 3.8, 95% CI 1.2-11.4, p = 0.015) among all participants. Environmental monitoring showed that beryllium particles were <1 µm, and this small fraction (0.1-1 µ) was significantly more highly accumulated in nuclear machining workers compared to dental technicians. The small fractions positively correlated with induced sputum macrophages (r = 0.21 p = 0.01) and negatively correlated with diffusion lung carbon monoxide single breath (DLCO-SB r = 0.180 p = 0.04) in all subjects. Years of exposure were positively correlated to the number of accumulated particles 2-3 µ in diameter (r = 0.2, p = 0.02) and negatively correlated to forced expiratory volume in one second/forced vital capacity findings (r = -0.18, p = 0.02). DLCO was decreased in both groups after two years of monitoring. Biological monitoring is more informative than environmental monitoring in the surveillance and monitoring of workers in beryllium industries. Induced sputum is a feasible and promising biomonitoring method that should be included in the surveillance of exposed workers.

Biological exposure metrics of beryllium-exposed dental technicians.

Beryllium is commonly used in the dental industry. This study investigates the association between particle size and shape in induced sputum (IS) with beryllium exposure and oxidative stress in 83 dental technicians. Particle size and shape were defined by laser and video, whereas beryllium exposure data came from self-reports and beryllium lymphocyte proliferation test (BeLPT) results. Heme oxygenase-1 (HO1) gene expression in IS was evaluated by quantitative polymerase chain reaction. A high content of particles (92%) in IS >5 µ in size is correlated to a positive BeLPT risk (odds ratio [OR] = 3.4, 95% confidence interval [CI]: 0.9-13). Use of masks, hoods, and type of exposure yielded differences in the transparency of IS particles (gray level) and modulate HO1 levels. These results indicate that parameters of size and shape of particles in IS are sensitive to workplace hygiene, affect the level of oxidative stress, and may be potential markers for monitoring hazardous dust exposures.

Beryllium disease among construction trade workers at Department of Energy nuclear sites.

BACKGROUND: A medical surveillance program was developed to identify current and former construction workers at significant risk for beryllium related disease from work at the DOE nuclear weapons facilities, and to improve surveillance among beryllium exposed workers. METHODS: Medical examinations included a medical history and a beryllium blood lymphocyte proliferation test (BeLPT). Stratified and multivariate logistic regression analyses were used to explore the risk of disease by age, race, trade, and reported work in buildings where beryllium was used. After adjusting for covariates, the risk of BeS was significantly higher among boilermakers, roofers, and sheet metal workers, as suggested in the stratified analyses. Workers identified as sensitized to beryllium were interviewed to determine whether they had been subsequently diagnosed with chronic beryllium disease. RESULTS: Between 1998 and December 31, 2010 13,810 workers received a BeLPT through the BTMed program; 189 (1.4%) were sensitized to beryllium, and 28 reported that they had had a compensation claim accepted for CBD. CONCLUSIONS: These data on former construction workers gives us additional information about the predictive value of the blood BeLPT test for detection of CBD in populations with lower total lifetime exposures and more remote exposures than that experienced by current workers in beryllium machining operations. Through this surveillance program we have identified routes of exposures to beryllium and worked with DOE site personnel to identity and mitigate those exposures which still exist, as well as helping to focus attention on the risk for beryllium exposure among current demolition workers at these facilities.

Long-term efficacy of a program to prevent beryllium disease.

BACKGROUND: In 2000, a manufacturer of beryllium materials and products introduced a comprehensive program to prevent beryllium sensitization and chronic beryllium disease (CBD). We assessed the program's efficacy in preventing sensitization 9 years after implementation. METHODS: Current and former workers hired since program implementation completed questionnaires and provided blood samples for the beryllium lymphocyte proliferation test (BeLPT). Using these data, as well as company medical surveillance data, we estimated beryllium sensitization prevalence. RESULTS: Cross-sectional prevalence of sensitization was 0.7% (2/298). Combining survey results with surveillance results, a total of seven were identified as sensitized (2.3%). Early Program workers were more likely to be sensitized than Late Program workers; one of the latter was newly identified. All sensitization was identified while participants were employed. One worker was diagnosed with CBD during employment. CONCLUSIONS: The combination of increased respiratory and dermal protection, enclosure and improved ventilation of high-risk processes, dust migration control, improved housekeeping, and worker and management education showed utility in reducing sensitization in the program's first 9 years. The low rate (0.6%, 1/175) among Late Program workers suggests that continuing refinements have provided additional protection against sensitization compared to the program's early years.

Occupational exposure to beryllium and cancer risk: a review of the epidemiologic evidence.

There is controversy on whether occupational exposure to beryllium causes lung cancer. We conducted a systematic review of epidemiologic studies on cancer among workers exposed to beryllium, including a study of seven U.S. production plants which has been recently updated, a study of patients with beryllium disease (largely overlapping with the former study) and several smaller studies. A small excess mortality from lung cancer was detected in the large cohort, which was partially explained by confounding by tobacco smoking and urban residence. Other potential confounders have not been addressed. The excess mortality was mainly among workers employed (often for a short duration) in the early phase of the manufacturing industry. There was no relation with duration of employment or cumulative exposure, whereas average and maximum exposure were associated with lung cancer risk. The use of lagged exposure variables resulted in associations with lung cancer risk; however, these associations were due to confounding by year of birth and year of hire. The studies of beryllium disease patients do not provide independent evidence and the results from other studies do not support the hypothesis of an increased risk of lung cancer or any other cancer. Overall, the available evidence does not support a conclusion that a causal association has been established between occupational exposure to beryllium and the risk of cancer.

Sensitization and chronic beryllium disease at a primary manufacturing facility, part 2: validation of historical exposures.

OBJECTIVE: The aim of this study was to evaluate the validity of a job exposure matrix (JEM) constructed for the period 1994-1999. Historical exposure estimates (HEE) for the JEM were constructed for all job and year combinations by applying temporal factors reflecting annual change in area air measurements (1994-1998) to the personal baseline exposure estimates (BEE) collected in 1999. The JEM was generated for an epidemiologic study to examine quantitative exposure-response relationships with sensitization and chronic beryllium disease. METHODS: The validity of the BEE and HEE was evaluated by comparing them with a validation dataset of independently collected personal beryllium exposure measurements from 1999 and 1994-1998, respectively. Agreement between the JEM and validation data was assessed using relative bias and concordance correlation coefficients (CCC). RESULTS: The BEE and HEE overestimated the measured exposures in their respective validation datasets by 8% and 6%, respectively. The CCC reflecting the deviation of the fitted line from the concordance line, showed good agreement for both BEE (CCC=0.80) and HEE (CCC=0.72). Proportional difference did not change with exposure levels or by process area and year. Overall, the agreement between the JEM and validation estimates (from combined HEE and BEE) was high (CCC=0.77). CONCLUSIONS: This study demonstrated that the reconstructed beryllium exposures at a manufacturing facility were reliable and can be used in epidemiologic studies.