Sensitization and chronic beryllium disease at a primary manufacturing facility, part 3: exposure–response among short-term workers

Schuler, Christine R.; Virji, M. Abbas; Deubner, David C.; Stanton, Marcia L.; Stefaniak, Aleksandr B.; Day, Gregory A.; Park, Ji Young; Kent, Michael S.; Sparks, Rachel; Kreiss, Kathleen

doi:10.5271/sjweh.3192

Cited by 38 publications

(30 citation statements)

References 26 publications

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“…Only ~2-10% of exposed workers develop BeS or CBD, and there has been a lack of a clear linear exposure response relationship noted in most, but not all, studies to date (7)(8)(9). This observation has led researchers to investigate genetic factors that might increase the risk of disease and sensitization.…”

mentioning

confidence: 99%

Chronic Beryllium Disease, HLA DPB1 And The DP Peptide Binding Groove

Silveira¹,

McCanlies²,

Fingerlin³

et al. 2011

C54. Hypersensitivity Pneumonitis and Berylliosis

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Multiple epidemiologic studies demonstrate associations between chronic beryllium disease (CBD), beryllium sensitization (BeS), and HLA-DPB1 alleles with a glutamic acid residue at position 69 (E69). Results suggest that the less-frequent E69 variants (non-*0201/*0202 alleles) might be associated with greater risk of CBD. In this study, we sought to define specific E69-carrying alleles and their amino acid sequences in the DP peptide binding groove, as well as their relationship to CBD and BeS risk, using the largest case control study to date. We enrolled 502 BeS/CBD subjects and 653 beryllium-exposed controls from three beryllium industries who gave informed consent for participation. Non-Hispanic white cases and controls were frequencymatched by industry. HLA-DPB1 genotypes were determined using sequence-specific primer PCR. The E69 alleles were tested for association with disease individually and grouped by amino acid structure using logistic regression. The results show that CBD cases were more likely than controls to carry a non-*02 E69 allele than an *02 E69, with odds ratios (95% confidence interval) ranging from 3.1 (2.1-4.5) to 3.9 (2.6-5.9) (p < 0.0001). Polymorphic amino acids at positions 84 and 11 were associated with CBD: DD versus GG, 2.8 (1.8-4.6), p < 0.0001; GD versus GG, 2.1 (1.5-2.8), p < 0.0001; LL versus GG, 3.2 (1.8-5.6), p < 0.0001; GL versus GG, 2.8 (2.1-3.8), p < 0.0001. Similar results were found within the BeS group and CBD/BeS combined group. We conclude that the less frequent E69 alleles confer more risk for CBD than does *0201. Recent studies examining how the composition and structure of the binding pockets influence peptide binding in MHC genes, as well of studies showing the topology of the TCR to likely bind DPB1 preferentially, give plausible biological rationale for these findings.Copyright © 2012 by The American Association of Immunologists, Inc.Address correspondence and reprint requests to: Dr. Lori J. Silveira, National Jewish Health, 1400 Jackson, Denver, CO 80206. silveiral@njhealth.org. DisclosuresThe authors have no financial conflicts of interest. HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptChronic beryllium disease (CBD) is an immunologic lung disease caused by inhalation of beryllium dust and fume (1). Exposed workers can develop beryllium sensitization (BeS), a beryllium-specific, cell-mediated immune response, which is measured by the beryllium lymphocyte proliferation test (BeLPT) (2-5). Once workers develop BeS, they may subsequently develop CBD, a diffuse lung disease characterized by granulomatous inflammation in the lung. Differentiation between CBD and BeS is determined by performing a clinical evaluation consisting of a lung biopsy and bronchoalveolar lavage. BeS precedes CBD, and it is estimated that between 3 and 9% (6) of those who are sensitized progress to disease each year. Beryllium exposure is necessary for sensitization and disease, but not all who are exposed develop sensitization and not all ...

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confidence: 99%

Chronic Beryllium Disease, HLA DPB1 And The DP Peptide Binding Groove

Silveira¹,

McCanlies²,

Fingerlin³

et al. 2011

C54. Hypersensitivity Pneumonitis and Berylliosis

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“…In 1999, a sub-cohort of 264 short-term workers hired after 1 January 1994 at a beryllium manufacturing facility was surveyed to assess the relationship between beryllium exposure and BeS and CBD (30). A JEM for the period 1994-1999 was constructed for personal total exposure (from 37 mm closed-face cassettes) as well as respirable and submicron (<1 µm) particle beryllium mass concentrations (from personal impactor samplers).…”

Section: Methodsmentioning

confidence: 99%

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

Virji²,

Ab³

et al. 2011

Scand J Work Environ Health

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“…Survey instruments included: medical and work-history questionnaires, blood samples to test for BeS, and clinical evaluation of sensitized workers for CBD; these are reported in detail in the companion paper (13). Historical beryllium exposures were reconstructed for the short-term workers using a job-exposure matrix (JEM) and work history information from their date of hire to either (i) their date of diagnosis or (ii) the date of the survey in 1999.…”

Section: Methodsmentioning

confidence: 99%

“…Creation of summary exposure metrics. Each study participant's work-tenure exposure profiles for the different size beryllium particles (CFC total, respirable, and submicron particles) were summarized for use in epidemiologic analyses (13). A series of summary exposure metrics were created to examine possible relationships of these metrics to biologically plausible exposure fac-…”

Section: Generating Personal Exposure Estimatesmentioning

confidence: 99%

“…The general area data (N=76 349 for the years 1994-1999) were collected from 274 fixed locations within the 24 process areas (identified in table 1) across all production and selected non-production units. General area air samples were collected using three sampling methods including: high volume (200-400 Lpm), continuous (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), and low-flow (2 Lpm) sampling methods (14). While information on sampling methods was not available, sampling durations of the general area samples included: 1-5 days (4.5%), 10-24 hours (10%), 6-10 hours (76%), <6 hours (9.5%).…”

Section: Data Sourcesmentioning

confidence: 99%

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