Screening Blood Test Identifies Subclinical Beryllium Disease

Kreiss, Kathleen; Newman, Lee S.; Mroz, Margaret M.; Campbell, Priscilla A.

doi:10.1097/00043764-198907000-00011

Cited by 157 publications

(113 citation statements)

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“…Beryllium has been used in the nuclear industry for a number of years. The epidemiology of CBD was examined in a stratified sample of workers at a nuclear weapons plant and the role of the BeLPT in beryllium disease surveillance in the nuclear industry was discussed (Kreiss et al, 1989). The U.S. Department of Energy is operating a screening program for CBD that will eventually include approximately 40 000 current and former beryllium-exposed workers at 20 Department of Energy sites.…”

Section: Introductionmentioning

confidence: 99%

Identification of an abnormal beryllium lymphocyte proliferation test

Frome¹,

Newman²,

Cragle³

et al. 2003

Toxicology

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The potential hazards from exposure to beryllium or beryllium compounds in the workplace were first reported in the 1930s. The tritiated thymidine beryllium lymphocyte proliferation test (BeLPT) is an in vitro blood test that is widely used to screen beryllium exposed workers in the nuclear industry for sensitivity to beryllium. The clinical significance of the BeLPT was described and a standard protocol was developed in the late 1980s. Cell proliferation is measured by the incorporation of tritiated thymidine into dividing cells on two culture dates and using three concentrations of beryllium sulfate. Results are expressed as a 'stimulation index' (SI) which is the ratio of the amount of tritiated thymidine (measured by beta counts) in the simulated cells divided by the counts for the unstimulated cells on the same culture day. Several statistical methods for use in the routine analysis of the BeLPT were proposed in the early 1990s. The least absolute values (LAV) method was recommended for routine analysis of the BeLPT. This report further evaluates the LAV method using new data, and proposes a new method for identification of an abnormal or borderline test. This new statistical Á/biological positive (SBP) method reflects the clinical judgment that: (i) at least two SIs show a 'positive' response to beryllium; and (ii) that the maximum of the six SIs must exceed a cut-point that is determined from a reference data set of normal individuals whose blood has been tested by the same method in the same serum. The new data is from the Y-12 National Security Complex in Oak Ridge (Y-12) and consists of 1080 workers and 33 nonexposed control BeLPTs (all tested in the same serum). Graphical results are presented to explain the statistical method, and the new SBP method is applied to the Y-12 group. The true positive rate and specificity of the new method were estimated to be 86% and 97%, respectively. An electronic notebook that is accessible via the Internet was used in this work and contains background information and details not included in the paper. #

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Section: Introductionmentioning

confidence: 99%

Identification of an abnormal beryllium lymphocyte proliferation test

Frome¹,

Newman²,

Cragle³

et al. 2003

Toxicology

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“…New cases continue to be identified despite historical improvements in workplace exposure conditions. Following exposure to beryllium, between 1 and 16% of exposed workers become sensitized to beryllium, as demonstrated using an in vitro measure of the berylliumspecific cell-mediated immune response called the beryllium lymphocyte proliferation test (BeLPT), formerly the beryllium lymphocyte transformation test (1)(2)(3)(4)(5)(6)(7). T lymphocytes recognize beryllium as an antigen triggering cell proliferation, release of inflammatory mediators, and accumulation of inflammatory cells in the target organ.…”

Section: Introductionmentioning

confidence: 99%

“…We have conducted studies of 3 groups to date: a pilot study of nuclear weapons workers, a subsequent study of 895 of these workers, and population-based studies in two beryllia ceramics plants. Through this series of investigations, Kreiss, Newman, and coworkers demonstrated that it was possible to identify individuals who are sensitized but who do not have disease, to identify individuals with subclinical illness, and to correct missed diagnoses in more advanced cases of disease (2,3,6,22). In one of these population-based studies, we examined the positive and negative predictive value of the various clinical tests that physicians use to screen for beryllium disease in industry (3).…”

Section: Introductionmentioning

confidence: 99%

The natural history of beryllium sensitization and chronic beryllium disease.

Newman

Lloyd

Daniloff

1996

Environ Health Perspect

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With the advent of in vitro immunologic testing, we can now detect exposed individuals who are sensitized to beryllium and those who have chronic beryllium disease (CBD) with lung pathology and impairment. Earlier detection and more accurate diagnostic tools raise new questions about the natural history of sensitization and granulomatous disease. Preliminary data suggest that early detection identifies people who are sensitized to beryllium and that these individuals are at risk for progressing into clinical disease. This article discusses the historical, recent, and ongoing studies germane to our understanding of CBD natural history, including the immunologic and inflammatory basis of the disease, the environmental and host risk factors for disease progression, biological markers of disease severity and activity that may help predict outcome, and the implications for broad-based workplace screening to identify patients at the earliest stages of beryllium sensitization and disease. Environ Health Perspect 104(Suppl 5): 937-943 (1996)

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“…In particular, beryllium has been used in the nuclear industry for a number of years. Kreiss et al (4) have examined the epidemiology of CBD in a stratified sample of workers at a nuclear weapons plant and discuss the role of the BeLPT in beryllium disease surveillance in the nuclear industry. The U.S. Department of Energy (DOE) is operating a screening program for CBD that will eventually include approximately 15,000 current and former beryllium-exposed workers at 20 DOE sites.…”

Section: Introductionmentioning

confidence: 99%

Statistical methods for the blood beryllium lymphocyte proliferation test.

Frome

Smith

Littlefield

et al. 1996

Environ Health Perspect

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The blood beryllium lymphocyte proliferation test (BeLPT) is a modification of the standard lymphocyte proliferation test that is used to identify persons who may have chronic beryllium disease. A major problem in the interpretation of BeLPT test results is outlying data values among the replicate well counts ( 7%). A log-linear regression model is used to describe the expected well counts for each set of Be exposure conditions, and the variance of the well counts is proportional to the square of the expected count. Two outlier resistant regression methods are used to estimate stimulation indices (SIs) and the coefficient of variation. The first approach uses least absolute values (LAV) on the log of the well counts as a method for estimation; the second approach uses a resistant regression version of maximum quasi-likelihood estimation. A major advantage of these resistant methods is that they make it unnecessary to identify and delete outliers. These two new methods for the statistical analysis of the BeLPT data and the current outlier rejection method are applied to 173 BeLPT assays. We strongly recommend the LAV method for routine analysis of the BeLPT.Outliers are also important when trying to identify individuals with beryllium hypersensitivity, since these individuals typically have large positive SF values. A new method for identifying large SIs using combined data from the not exposed group and the beryllium workers is proposed. The log(SI)s are described with a Gaussian distribution with location and scale parameters estimated using resistant methods. This approach is applied to the test data and results are compared with those obtained from the current method.

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Screening Blood Test Identifies Subclinical Beryllium Disease

Cited by 157 publications

References 0 publications

Identification of an abnormal beryllium lymphocyte proliferation test

Identification of an abnormal beryllium lymphocyte proliferation test

The natural history of beryllium sensitization and chronic beryllium disease.

Statistical methods for the blood beryllium lymphocyte proliferation test.

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