Scientific publications either directly studying former workers in the context of the screening program or recruiting former workers in the program as research participants for scientific studies funded by the National Institutes of Health or other research funding sources are summarized below according to publication date.

Markowitz S., Manowitz A., Miller J., Frederick J., Onyekelu-Eze A., Widman S., Pepper L., Miller A. Yield of low-dose computerized tomography screening for lung cancer in high-risk workers: the case of 7189 US nuclear weapons workers. American Journal of Public Health, 2018.

A low-dose computerized tomography program among 7189 nuclear weapons workers in 9 nonmetropolitan US communities during 2000 to 2013 was implemented. Eligibility criteria included age, smoking, occupation, radiographic asbestos-related fibrosis, and a positive beryllium lymphocyte proliferation test. The proportion with screen-detected lung cancer among smokers aged 50 years or older was 0.83% at baseline and 0.51% on annual scan. Of 80 lung cancers, 59% (n = 47) were stage I, and 10% (n = 8) were stage II. Screening yields of study sub-populations who met the National Lung Screening Trial or the National Comprehensive Cancer Network Group 2 eligibility criteria were similar to those found in the National Lung Screening Trial. Computerized tomography screening for lung cancer among high-risk workers leads to a favorable yield of early-stage lung cancers.

Dement J., Welch L., Ringen K., Cranford K., Quinn P. Hearing loss among older construction workers: updated analyses. American Journal of Industrial Medicine, 2018.

Among participants (n=19,127) an overall prevalence of hearing loss of 58% was observed, with significantly increased prevalence across all construction trades. Construction workers had significantly increased risk of hearing loss compared to reference populations, with increasing risk by work duration. Noise exposure, solvent exposure, hypertension, and smoking were significant risk factors in multivariate models.

Phillips A., Frank A., Loftin C., Shepherd S. A detailed review of systems: an educational feature. The Journal of Nurse Practitioners, 13(10): 681-686, 2017.

Assessment is the foundation of health care. A goal in health care is to attain a comprehensive history and review of systems during the first encounter with the patient. The evidence-based recommendations presented in this article are informed by unpublished data from real-life experiences using a detailed review of systems during an ongoing medical surveillance program involving former nuclear workers from a United States Department of Energy site.

Dement J., Welch S., Ringen K., Cranford K., Quinn P. Longitudinal decline in lung function among older construction workers. Occupational and Environmental Medicine, 2017.

High occupational exposures to vapors, gases, dust, and fumes (VGDF) are common in many construction tasks and trades. Cross-sectional studies have linked occupational VGDF exposures to declines in lung function and increased risk of COPD. Using data from the Building Trades National Medical Screening Program, which screens former workers at certain Department of Energy sites, researchers constructed a longitudinal study to measure this association. The authors gathered work history information, chest X-ray results, and spirometry test results from a population of 3,150 construction workers who received at least one follow-up examination after initial intake. Workers with a history of high or intermediate VGDF exposures on the job had poorer lung function at their initial screening than those with a history of low VGDF exposures. In the years following the initial screening, lung function declined more quickly in workers with a history of high or intermediate VGDF exposures than those with a history of low VGDF exposures. Pleural plaque, even in the absence of Diffuse Pleural Thickening, was associated with a decline in lung function.

Welch S., Dement J., Ringen K., Cranford K., Quinn P. Impact of secondary prevention in an occupational high-risk group. American College of Occupational and Environmental Medicine, 59:67-73, 2017.

A study of medical outcomes among 6,857 elderly construction workers who receive an initial and at least one periodic follow-up examination as a result of participating in a medical screening program was undertaken.  The authors compared results from the initial examination to follow-up examinations delivered at least 3 years after the initial examination for the following outcomes:  body mass index, total serum cholesterol, non-high-density lipoprotein cholesterol, hemoglobin A1c, hypertension, current cigarette smoking, and 10-year cardiovascular disease risk scores. Statistically significant improvements were observed for all measures except BMI.

Stange B., McInerney J., Golden A., Benade W., Neill B., Mayer A., Witter R., Tenney L., Stinson K., Cragle D., Newman L. Integrated approach to health screening of former Department of Energy workers detects both occupational and non-occupational illness. American Journal of Industrial Medicine, 59:200-211, 2016.

The National Supplemental Screening Program (NSSP) uses A Total Worker Health™ approach to address U.S. Department of Energy (DOE) former worker health.  The NSSP presented medical findings for 12,000 DOE former workers that completed an initial NSSP medical screening between October 1, 2005, and October 4, 2013.  The NSSP identified potential occupationally related health conditions in 40.5% of those screened and identified 85.8% of participants with addressable non-occupational health conditions, many of which were previously undiagnosed.  The NSSP demonstrates that the identification of potential occupational health issues in conjunction with addressable non-occupational health conditions provides former workers with information to more effectively manage health.

Dement J., Welch L., Ringen K., Quinn P., Chen A., Haas S. A case-control study of airways obstruction among construction workers. American Journal of Industrial Medicine 9999:1-15, 2015.

This case-control study estimated the risk of COPD attributable to occupational exposures among construction workers.  The study population included 834 cases and 1243 controls participating in a national medical screening program for older construction workers between 1997 and 2013.  Approximately 18% of COPD risk can be attributed to construction-related exposures, which are additive to the risk contributed by smoking.  Construction workers are at increased risk of COPD as a result of broad and complex effects of many exposures acting independently or interactively.  Control methods should be implemented to prevent worker exposures, and smoking cessation should be promoted.

Ringen K., Dement J., Welch L., Bingham E., Quinn P., Chen A., Haas S. Mortality of older construction and craft workers employed at Department of Energy (DOE) nuclear sites: follow-up through 2011. American Journal of Industrial Medicine, 58:152-167, 2015.

Workers participating in the Building Trades National Medical Screening Program (BTMed) between 1998 and 2011 were followed to determine their vital status and mortality experience through December 31, 2011. The cohort includes 18,803 BTMed participants and 2,801 deaths.  Mortality was elevated for all causes, all cancers, cancers of the trachea, bronchus, and lung and lymphatic and hematopoietic system, mesothelioma, chronic obstructive pulmonary disease, and asbestosis. Construction workers employed at DOE sites have a significantly increased risk for occupational illnesses.  Risks are associated with employment during all time periods covered including after 1980.

Dong X., Ringen K., Welch, L., Dement J. Risks of a lifetime in construction part 1: traumatic injuries. American Journal of Industrial Medicine, 2014.

Estimates of occupational risk are typically computed on an annual basis.  In contrast, this article provides estimates of lifetime risks for fatal and nonfatal injuries among construction workers.  Using 2003-2007 data from three large data sources, lifetime risk was computed based on the number of fatal and nonfatal injuries per 100 FTEs for a working lifespan of 45 years.  For a working life in construction, the risk of fatal injuries was approximately one death per 200 FTE, and the leading causes were falls and transportation incidents.  For nonfatal injuries resulting in days away from work, the adjusted lifetime risk was approximately 78 per 100 FTEs, and the leading causes were contact with objects/equipment, overexertion, and falls to a lower level.

Ringen K., Dement J., Welch W., Dong X., Bingham E., Quinn P. Risks of a lifetime in construction. Part II: chronic occupational diseases. American Journal of Industrial Medicine, 57: 1235-1245, 2014.

The authors developed working-life estimates of risk for dust-related occupational lung disease, COPD, and hearing loss based on the experience of the Building Trades National Medicine Screening Program in order to (1) demonstrate the value of estimates of lifetime risk, and (2) make lifetime risk estimates for common conditions among construction workers.  Estimates of lifetime risk were performed based on 12,742 radiographic evaluations, 12,679 spirometry tests, and 11,793 audiograms.  Over a 45-year working life, 16% of construction workers developed COPD, 11% developed parenchymal radiological abnormality, and 73.8% developed hearing loss.  The risk for occupationally related disease over a lifetime in a construction trades was 2-6 times greater than the risk in non-construction workers.

Mikulski M., Gerke A., Lourens S., Czeczok T., Sprince N., Laney A., Fuortes L. Agreement between fixed-ratio and lower limit of normal spirometry interpretation protocols decreases with age - Is there a need for a new gold standard? Journal of Occupational and Environmental Medicine, 55(7): 802-808, 2013.

To assess concordance between the fixed 70% ratio cutoff point with the fixed percent predicted values (Fixed-ratio) and the lower limit of normal (LLN) algorithms in interpreting spirometry results in an older population, spirometries were interpreted using Third National Health and Nutrition Examination Survey reference equations for 2,319 workers. The Fixed-ratio algorithm characterized 34.5% (n=801) results as abnormal, compared with 29.7% (n=689) by the LLN. There were almost twice as many obstructive and mixed airways spirometries identified under the Fixed-ratio compared to LLN. Rates of restrictive pattern physiology were virtually the same under each algorithm. Overall agreement between the algorithms decreased with age from "almost perfect" for those younger than 60 years to "substantial" for those older than 80 years. This study found age-related discordance between two algorithms possibly related to the lack of reference equations and standards for individuals older than 80 years.

Welch L., Ringen K., Dement J., Bingham E., Quinn P., Shorter J., Fisher M. Beryllium disease among construction trade workers at Department of Energy nuclear sites. American Journal of Industrial Medicine, 2013. [E-published ahead of print]

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. 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 beryllium sensitization 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 (CBD). Between 1998 and December 31, 2010, 13,810 workers received a BeLPT through the surveillance program; 189 (1.4%) were sensitized to beryllium, and 28 reported that they had had a compensation claim accepted for CBD. These data on former construction workers gives the authors 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.

Manowitz A., Sedlar M., Griffon M., Miller A., Miller J., Markowitz S. Use of BMI guidelines and individual dose tracking to minimize radiation exposure from low-dose helical chest CT scanning in a lung cancer screening program. Academic Radiology, 19(1): 84-88, 2012.

The increasing use of computed tomography (CT) has been accompanied by rising concerns over potential radiation-related health risks, especially cancer, and a need to minimize such risks. The authors conducted 2,186 low-dose helical chest CT scans among 1,235 nuclear weapons workers at elevated risk of lung cancer, setting the CT scanner tube current at 30 mAs for all participants with Body Mass Index (BMI) <35 kg/m2 and permitting technologists to raise mAs levels for participants with BMI ≥35 kg/m2. Dose-length product (DLP) was recorded from the CT scanner, permitting calculation of effective dose. Phantom-based estimates of effective dose were also made. A chest radiologist recorded acceptability of image quality. The study population was significantly overweight. Nearly 90% of CT scans were performed using a tube current setting of 30 mAs and had a mean DLP-based effective dose of 1.3 mSv. The phantom-based estimate of effective dose was lower at 1.1 mSv. Among participants with a BMI ≥35 kg/m2, 92% were scanned at 40 or 50 mAs, which was associated with a DLP-based effective dose of 1.6 and 2.0 mSv, respectively. Image quality was satisfactory in 99.8% of scans. Application of simple BMI-based guidelines and DLP tracking of low-dose helical chest CT scans in a lung cancer screening program minimizes radiation dose, even in a largely overweight population.

Leavey A., Frank A., Pinson B., Shepherd S., and Burstyn I. Hypothyroidism among former workers of a nuclear weapons facility. American Journal of Industrial Medicine, 54(12):955-964, 2011.

Hypothyroid status was determined for 622 former workers of a nuclear weapons facility located in Texas, using a combination of measured thyroid stimulating hormone (TSH) levels and thyroid medication history, as part of an on-going health surveillance program. The authors classified 916 unique job titles into 35 job categories. According to the most stringent TSH definition used in this study (0.3-3.0 IU/ml), 174 (28.0%) former workers were considered to be hypothyroid; of these, 66 (41.8%) were females and 108 (23.3%) were males. In logistic regression analysis adjusted for age, gender, and smoking status, only having worked as a material handler (n = 18) exhibited an elevated risk of developing hypothyroidism compared to other jobs (OR 3.88, 95% CI 1.43-11.07). Material handlers perform a job that has suspected exposure to radiation. No excess risk of hypothyroidism was observed for any of the other job categories. There is suggestive evidence that only material handlers at this nuclear weapons facility may have elevated risk of hypothyroidism; further evaluation of thyroid health in this population is warranted. 

Mikulski M., Hartley P., Sprince N., Sanderson W., Lourens S., Worden N., Wang K., and Fuortes L. Risk and significance of chest radiograph and pulmonary function abnormalities in an elderly cohort of former nuclear weapons workers. Journal of Occupational and Environmental Medicine, 53(9):1046-53, 2011.

A study to estimate prevalence and risk factors for International Labour Organization radiographic abnormalities and assess relationship of these abnormalities with spirometry results in former U.S. Department of Energy (DOE) nuclear weapons workers was undertaken. Participants were offered chest x-ray and lung function testing. Three occupational medicine physicians read the chest x-rays. Forty-five (5.9%) of the 757 screened workers were found to have isolated parenchymal abnormalities on chest x-ray; this rate is higher than that in many DOE studies. Parenchymal and pleural abnormalities and isolated pleural abnormalities were found in 19 (2.5%) and 37 (4.9%) workers, respectively, and these rates are lower than those in other DOE studies to date. Lung function impairment was associated with radiographic abnormalities. This study found an elevated rate of parenchymal abnormalities compared to other DOE populations, but the effect of age or other causes could not be ruled out. 

Mikulski M., Leonard S., Sanderson W., Hartley P., Sprince N., and Fuortes L. Risk of beryllium sensitization in a low-exposed former nuclear weapons cohort from the cold war era. American Journal of Industrial Medicine; 2010 October 28. [E-published ahead of print]

The nuclear weapons industry has long been known as a source of beryllium exposure. A total of 1,004 former workers from a nuclear weapons assembly site at the Iowa Army Ammunition Plant were screened for sensitization to beryllium. Twenty-three (2.3%) workers were found sensitized to beryllium, and this prevalence was comparable to other U.S. Department of Energy sites. Occasional, direct exposure to beryllium through machining and grinding of copper-beryllium 2% alloy tools was found to increase the risk of sensitization compared to background exposure (OR=3.83; 95% CI: 1.04-14.03) with a statistically significant trend (P=0.03) revealing that particular jobs are associated with sensitization. Exposure potential in this study was estimated based on job titles and not personal exposure information. 

Dement J., Welch L., Ringen K., Bingham E., and Quinn P. Airways obstruction among older construction and trade workers at Department of Energy nuclear sites. American Journal of Industrial Medicine, 53:224-240, 2010.

A study of chronic obstructive pulmonary disease (COPD) among 7,579 current and former workers participating in medical screening programs at U.S. Department of Energy (DOE) nuclear weapons facilities through September 2008 was undertaken. Participants provided a detailed work and exposure history and underwent a respiratory examination that included a respiratory history, respiratory symptoms, a posterior-anterior chest radiograph classified by International Labour Organization criteria, and spirometry. The study of construction workers employed at DOE sites demonstrated increased COPD risk due to occupational exposures and was able to identify specific exposures increasing risk.

Dement J., Ringen K., Welch L., Bingham E., and Quinn P. Mortality among older construction and craft workers employed at Department of Energy (DOE) sites. American Journal of Industrial Medicine, 52:671-682, 2009.

A cohort of 8,976 former construction workers from Hanford Site, Savannah River Site, Oak Ridge, and Amchitka was followed using the National Death Index through December 31, 2004, to ascertain vital status and causes of death. DOE construction workers at these four sites were found to have significantly excess risk for combined cancer sites included in the Department of Labor Energy Employees Occupational Illness Compensation Program. Asbestos-related cancers were significantly elevated. 

Dobis D.R., Sawyer R.T., Gillespie M.M., Huang J., Newman L.S., Maier L.A., Day B.J. Modulation of lymphocyte proliferation by antioxidants in chronic beryllium disease. American Journal of Respiratory and Critical Care Medicine, 177(9):1002-11, 2008.

Occupational exposure to beryllium can result in chronic granulomatous inflammation characterized by the presence of beryllium-specific CD4+ T cells. Studies show that oxidative stress plays a role in the pathogenesis of chronic inflammatory disorders. Thirty-three subjects with chronic beryllium disease (CBD), 15 subjects with beryllium sensitization, and 28 healthy normal control subjects were consecutively enrolled from the Occupational and Environmental Health Clinic of National Jewish Health. The authors concluded that beryllium can mediate a thiol imbalance leading to oxidative stress that may modulate the proliferation and clonal expansion of beryllium-specific blood CD4+ T cells. These data suggest that beryllium-induced oxidative stress plays a role in the pathogenesis of granulomatous inflammation in CBD. 

Rodrigues E., McClean M., Weinberg J., and Pepper L. Beryllium sensitization and lung function among former workers at the Nevada Test Site. American Journal of Industrial Medicine, 51:512-523, 2008.

Beryllium use at the Nevada Test Site was not acknowledged until the late 1990s. An observational study was conducted to identify work-related factors associated with the odds of having beryllium sensitization (BeS). Among the 1,786 former workers tested for BeS, the prevalence of BeS was 1.3%. An increased risk of BeS was found among workers who performed cleanup (OR = 2.68, 95% confidence interval [CI]: 1.10, 6.56) and those who worked in Building B where beryllium parts were machined (OR = 2.52, 95% CI: 1.02, 6.19).

Markowitz S.B., Miller A., Miller J., Manowitz A., Kieding S., Sider L., and Morabia A. Ability of low-dose helical computed tomography to distinguish between benign and malignant non-calcified lung nodules. Chest, 131:1028-1034, 2007.

Low-dose helical computed tomography (CT) scanning identifies early stage lung malignancies and also a large proportion of lung nodules of uncertain diagnostic and prognostic significance (i.e., indeterminate nodules). In this study, a total of 4,401 participants were CT scanned for lung cancer with an initial full-chest low-dose CT scan; interval CT scans at 3, 6, and 12 months for indeterminate lung nodules (e.g., nodules not immediately suspicious for lung cancer); and an 18-month, full-chest, low-dose incidence CT scan. Only 3 of 727 indeterminate nodules were identified as being malignant during the subsequent 18 months. The radiologist's designation of a nodule as suspicious had a sensitivity of 84.2% and a specificity of 96.6%. Overall, the authors detected 33 primary lung cancers, including 19 stage I cancers, 5 stage II cancers, 7 stage III-IV cancers, and 3 limited-stage small cell cancers.

Sato H., Spagnolo P., Silveira L., Welsh K.I., du Bois R.M., Newman L.S., Maier L.A. BTNL2 allele associations with chronic beryllium disease in HLA-DPB1*Glu69-negative individuals. Tissue Antigens, 70(6):480-6, 2007.

Butyrophilin-like 2 (BTNL2) polymorphisms have been associated with sarcoidosis. Genomic DNA was obtained from chronic beryllium disease (CBD, n= 88), beryllium sensitized (BeS, n= 86), and beryllium exposed nondiseased control subjects (Be-exp, n= 173). The authors concluded that both DRB1*13 and rs3117099TT homozygosity are associated with CBD in *Glu69-negative subjects, while DPB1*Glu69 is associated with CBD and BeS compared with Be-exp. As a result of the small sample size and strong linkage disequilibrium between DRB1*13-DQB1*0603/4/9 and the BTNL2 rs3117099T allele, it is difficult to assess the primary association in DPB1*Glu69-negative CBD cases.

Sawyer R.T., Fontenot A.P., Barnes T.A., Parsons C.E., Tooker B.C., Maier L.A., Gillespie M.M., Gottschall E.B., Silveira L., Hagman J., and Newman L.S. Beryllium-induced TNF-alpha production is transcription-dependent in chronic beryllium disease. American Journal of Respiratory Cell and Molecular Biology, 36(2):191-200, 2007.

Beryllium-antigen presentation to beryllium-specific CD4(+) T cells from the lungs of patients with chronic beryllium disease (CBD) results in T cell proliferation and TNF-alpha secretion. The authors tested the hypothesis that beryllium-induced, CBD bronchoalveolar lavage T cell, transcription-dependent, TNF-alpha secretion was accompanied by specific transcription factor upregulation. The data suggest that beryllium exposure induces transcription-dependent TNF-alpha production, potentially due to upregulation of specific transcription factors. 

Bingham E., Ringen K., Dement J., Cameron, W., McGowan W., Welch, L., and Quinn, P. Frequency and quality of radiation monitoring at two gaseous diffusion plants. Annals of the New York Academy of Sciences, 1076:394-404, 2006.

Since World War II, large numbers of construction workers were employed at U.S. Department of Energy nuclear weapons sites, performing tasks during new construction and maintenance, repair, renovation, and demolition of existing facilities. Such tasks may have involved emergency situations and may have entailed opportunities for significant radiation exposures. This paper provides data from interviews with more than 750 construction workers at two gaseous diffusion plants at Paducah, Kentucky, and Portsmouth, Ohio, regarding radiation monitoring practices.

Dement J., Ringen K., Welch L., Bingham E., and Quinn P. Surveillance of hearing loss among construction and trade workers at Department of Energy nuclear sites. American Journal of Industrial Medicine, 48:348-358, 2005.

Medical screening programs for construction workers at Hanford Site, Oak Ridge, and Savannah River Site have included audiometric testing since approximately 1996. Hearing thresholds among U.S. Department of Energy workers examined before 3/31/03 were much higher than observed in a comparison population of industrial workers with low noise exposures. Overall, 59.7% of workers examined were found to have material hearing impairment by National Institute for Occupational Safety and Health criteria. Age, duration of construction work, smoking, and self-reported noise exposure increased the risk of hearing loss. 

Fontenot A.P., Palmer B.E., Sullivan A.K., Joslin F.G., Wilson C.C., Maier L.A., Newman L.S., and Kotzin B.L. Frequency of beryllium-specific, central memory CD4+ T cells in blood determines proliferative response. The Journal of Clinical Investigation, 115(10):2886-93, 2005.

Beryllium exposure can lead to the development of beryllium-specific CD4+ T cells and chronic beryllium disease (CBD), which is characterized by the presence of lung granulomas and a CD4+ T cell alveolitis. Studies have documented the presence of proliferating and cytokine-secreting CD4+ T cells in blood of CBD patients after beryllium stimulation. However, some patients were noted to have cytokine-secreting CD4 T cells in blood in the absence of beryllium-induced proliferation, and overall, the correlation between the two types of responses was poor. The authors hypothesized that the relative proportion of memory T cell subsets determined antigen-specific proliferation. In most CBD patients, the majority of beryllium-specific CD4+ T cells in blood expressed an effector memory T cell maturation phenotype. However, the ability of blood cells to proliferate in the presence of beryllium strongly correlated with the fraction expressing a central memory T cell phenotype. In addition, the authors found a direct correlation between the percentage of beryllium-specific CD4+ T(EM) cells in blood and T cell lymphocytosis in the lung. Together, these findings indicate that the functional capability of antigen-specific CD4+ T cells is determined by the relative proportion of memory T cell subsets, which may reflect internal organ involvement.

Makie T., Adcoc D., Lackland D., and Hoel D.G. Pulmonary abnormalities associated with occupational exposures at the Savannah River Site. American Journal of Industrial Medicine, 48:365-372, 2005.

This study includes data from 1,368 former Savannah River Site (SRS) workers aged 45 years or older who were assessed regarding work history and exposures to industrial agents. Chest radiographs were evaluated by a single radiologist, and the results were compared with the National Health and Nutrition Examination Survey (NHANES) II results. The odds ratio of the SRS male aged 45-75 compared to NHANES was 2.4 for pleura abnormalities and 0.8 for parenchymal abnormalities. The highest-risk worker division was construction (OR = 2.76). Asbestos and possibly other exposures were related to pulmonary disease in this population.

Newman L.S., Mroz M.M., and Ruttenber A.J. Lung fibrosis in plutonium workers. Radiation Research, 164(2):123-31, 2005.

There have been few systematic studies of the non-malignant health effects of alpha-particle radiation in humans. Animal studies and a report on plutonium-exposed workers from Russia suggest an association between high doses to the lung from plutonium exposure and the development of fibrotic lung disease. Prompted by a case of lung fibrosis in a retired plutonium worker, the authors tested the hypothesis that plutonium inhalation increases the risk for developing chest radiograph abnormalities consistent with pulmonary fibrosis. A retrospective study of nuclear weapons workers was conducted that included estimating absorbed doses to the lung with an internal dosimetry model. The study population consisted of 326 plutonium-exposed workers with absorbed lung doses from 0 to 28 Sv and 194 unexposed workers. This study shows that plutonium may cause lung fibrosis in humans at absorbed lung doses above 10 Sv.

Newman L.S., Mroz M.M., Balkissoon R., and Maier L.A. Beryllium sensitization progresses to chronic beryllium disease: a longitudinal study of disease risk. American Journal of Respiratory Cell and Molecular Biology, 171(1):54-60, 2005.

The blood beryllium lymphocyte proliferation test is used in medical surveillance to identify both beryllium sensitization (BeS) and chronic beryllium disease (CBD). Approximately 50% of individuals with BeS have CBD at the time of their initial clinical evaluation; however, the rate of progression from BeS to CBD is unknown. The authors monitored a cohort of beryllium-sensitized patients at 2-year intervals, using bronchoalveolar lavage and repeated transbronchial lung biopsies to determine progression to CBD as evidenced by granulomatous inflammation in lung tissue. No difference was found in average age, sex, race or ethnicity, smoking status, or beryllium exposure time between those who progressed to CBD and those who remained sensitized without disease. The authors concluded that BeS is an adverse health effect in beryllium-exposed workers and merits medical follow-up.  

Pott G.B., Palmer B.E., Sullivan A.K., Silviera L., Maier L.A., Newman L.S., Kotzin B.L., and Fontenot A.P. Frequency of beryllium-specific, TH1-type cytokine-expressing CD4+ T cells in patients with beryllium-induced disease. Journal of Allergy and Clinical Immunology, 115(5):1036-42, 2005.

Beryllium sensitization is caused by exposure to beryllium in the workplace. A subset of beryllium-sensitized (BeS) subjects progress to chronic beryllium disease (CBD), a disorder characterized by a CD4+ T-cell alveolitis and granulomatous inflammation. The aim of this study was to determine whether the quantity of beryllium-specific T cells in blood of patients with CBD differs from that found in BeS subjects. Beryllium-induced T-cell proliferation and TH1-type cytokine secretion were determined in blood cells from 33 patients with CBD and 18 BeS subjects. The study concluded that the frequency of beryllium-specific T cells in the blood of beryllium-exposed subjects may be a useful biomarker that helps discriminate between beryllium sensitization and progression to CBD.

Miller A., Markowitz S., Manowitz A., and Miller J.A. Lung cancer screening using low-dose high-resolution CT scanning in a high-risk workforce: 3500 nuclear fuel workers in three US states. Chest, 125(5 Suppl):152S-3S, 2004.

Past and present nuclear fuel workers with demonstrated or potential exposure to lung carcinogens (e.g., asbestos, radiation, and/or beryllium) have been screened for early lung cancer with a low-dose mobile CT scanner at three sites in the states of Kentucky, Ohio, and Tennessee. Indeterminate nodules on low-dose CT scans were re-scanned using a full-dose high-resolution technique. Patients with nodules that remained indeterminate were re-scanned at 3, 6, 12, and 18 months. Incidence screens were performed 18 months after the initial scan. The authors demonstrated the practicality of lung cancer screening using low-dose CT scanning in a large occupationally defined population in three states. The overall lung cancer rate was 20 of 3,598 subjects; 0.7%.

Sackett H.M., Maier L.A., Silveira L.J., Mroz M.M., Ogden L.G., Murphy J.R., and Newman L.S. Beryllium medical surveillance at a former nuclear weapons facility during cleanup operations. Journal of Occupational and Environmental Medicine, 46(9):953-61, 2004.

Despite the increasing need to remediate beryllium-contaminated buildings in industry, little is known about the magnitude of risk associated with beryllium abatement or the merits of beryllium medical surveillance for cleanup workers. The authors examined beryllium lymphocyte proliferation tests (BeLPTs) and reviewed medical evaluations of workers at a nuclear weapons facility during the process of decontamination and decommissioning. Of 2,221 workers, 19 (0.8%) were beryllium sensitized based on two or more abnormal BeLPTs. Eight of 19 sensitized individuals underwent full clinical evaluation, of whom two were diagnosed with chronic beryllium disease (CBD). Notably, seven beryllium sensitized and CBD cases were hired after the start of cleanup operations. Beryllium medical surveillance detects sensitization and CBD in cleanup workers. Exposure controls and medical surveillance need to be 'broad-based' to include all cleanup workers involved in beryllium-contaminated building remediation.

Sawyer R.T., Parsons C.E., Fontenot A.P., Maier L.A., Gillespie M.M., Gottschall E.B., Silveira L., and Newman L.S. Beryllium-induced tumor necrosis factor-alpha production by CD4+ T cells is mediated by HLA-DP. American Journal of Respiratory Cell and Molecular Biology, 31(1):122-30, 2004.

Beryllium presentation to CD4+ T cells from patients with chronic beryllium disease (CBD) results in T cell activation, and these beryllium-specific CD4+ T cells undergo clonal proliferation and T-helper 1-type cytokine production. In exposed workers, genetic susceptibility to this granulomatous disorder is associated with particular HLA-DPB1 alleles. The authors hypothesized that these HLA-DP molecules could mediate beryllium-stimulated tumor necrosis factor-alpha (TNF-alpha) messenger RNA (mRNA) and protein production. Using intracellular cytokine staining, the researchers found that treatment with an anti-HLA-DP, but not anti-HLA-DR, monoclonal antibody inhibited beryllium-stimulated TNF-alpha expression in lung CD3+ CD4+ T cells. This monoclonal antibody also blocked beryllium-specific T cell proliferation, increased production of TNF-alpha mature-mRNA transcripts, and increased TNF-alpha protein production by beryllium-stimulated CBD peripheral blood mononuclear cells and bronchoalveolar lavage (BAL) cells. The beryllium-stimulated upregulation of TNF-alpha mature-mRNA levels with TNF-alpha protein production was a unique property of CBD BAL cells, and did not occur in BAL cells from beryllium-sensitized patients without CBD, or sarcoidosis BAL cells. This study identifies HLA-DP as a regulatory component in the activation of T cell receptors on beryllium-specific CD4+ T cells from CBD patients resulting in proliferation and proinflammatory cytokine production.

Welch L., Ringen K., Bingham E., Dement J., Takaro T., McGowan W., Chen A., and Quinn P. Screening for beryllium disease among construction trade workers at Department of Energy nuclear sites. American Journal of Industrial Medicine, 46: 207-218, 2004.

Screening programs for construction workers were undertaken at the Hanford Site, Oak Ridge, and Savannah River Site. Of the 3,842 workers screened at and included in this study, 34% reported exposure to beryllium. Overall, 2.2% of workers had at least one abnormal beryllium lymphocyte proliferation test (BeLPT), and 1.4% were also abnormal on a second test. Regression analyses demonstrated increased risk of having at least one abnormal BeLPT to be associated with ever working in a site building where beryllium activities had taken place. The findings demonstrate that some of these workers had significant exposure, most likely during maintenance, repair, renovation, or demolition in facilities where beryllium was used.

Dement J., Welch L., Bingham E., Cameron B., Rice C., Quinn P., Ringen K. Surveillance of respiratory diseases among construction and trade workers at Department of Energy nuclear sites. American Journal of Industrial Medicine, 43:559-573, 2003.

Medical screening programs were begun in 1996 and 1997 at Hanford Site, Oak Ridge, and Savannah River Site to evaluate whether current and former construction workers are at significant risk for occupational illnesses. Of the 2,602 workers examined before 9/30/01, 25.2% showed one or more chest x-ray changes by International Labour Organization criteria and 42.7% demonstrated one or more pulmonary function defects. Although the observed respiratory disease patterns are largely reflective of past exposures, these findings suggest that DOE needs to continue to review industrial hygiene control programs for work tasks involving maintenance, repair, renovation, and demolition.

Stefaniak A.B., Weaver V.M., Cadorette M., Puckett L.G., Schwartz B.S., Wiggs L.D., Jankowski M.D., and Breysse P.N. Summary of historical beryllium uses and airborne concentration levels at Los Alamos National Laboratory. Applied Occupational and Environmental Hygiene. 18(9):708-15, 2003.

Beryllium operations and accompanying medical screening of workers at Los Alamos National Laboratory began in the 1940s. In 1999, a Former Worker Medical Screening Program (FWP) that includes screening for chronic beryllium disease was initiated. As part of this program, historical beryllium exposure conditions were reconstructed from archived paper and electronic industrial hygiene data sources to improve understanding of past beryllium uses and airborne concentration levels. A total of 4,528 personal breathing zone and area air samples for beryllium, combined for purposes of calculating summary statistics, were identified during the records review phase. The geometric mean airborne beryllium concentration for the period 1949-1989 for all technical areas was 0.04 µg Be/m3 with 97 % of all samples below the 2.0 µg Be/m3 occupational exposure limit. These data can be used to more effectively identify former worker populations at potential risk for chronic beryllium disease and to offer these workers screening as part of the FWP, and, in the event that a case is diagnosed, help to understand historical exposure conditions.

Breysse P., Weaver V., Cadorette M., Wiggs L., Curbow B., Stefaniak A., Melius J., Newman L., Smith H., and Schwartz B. Development of a medical examination program for former workers at a Department of Energy national laboratory. American Journal of Industrial Medicine, 42:443-454, 2002.

A needs assessment was conducted at Los Alamos National Laboratory (LANL) in order to identify former LANL employees who may be at significant risk for occupational disease and to determine whether a medical examination program could reduce morbidity or mortality. The algorithm approach that was developed documented that six chemical and physical agents should be included in the medical examination program.

Miller A., Markowitz S., Dahlgren J., Levin S., Swarcberg J., and Warshaw R. Early lung cancer detection using low dose high resolution CT in high risk workers occupationally exposed to asbestos: An overview of 3 studies. European Journal of Oncology, 6, 2001.

Lung cancer is the main cause of cancer mortality in both sexes, and its incidence continues to increase. Mortality is high due to the diffusion of disease at the time of diagnosis. Low-dose high-resolution computed tomography allowing the diagnosis of lesions <10 mm in diameter may bring about improvement of results. The authors present some studies and the results available with the use of this new technique.


Lokie Harmond, Program Manager