Analysis of single nucleotide polymorphisms in chronic beryllium disease

Sarcoidosis and chronic beryllium disease (CBD) are phenocopies, however the latter one has a clear trigger factor that is beryllium exposure. This study analyses single nucleotide polymorphisms (SNPs) in a large cohort for beryllium-exposed persons. SNPs were chosen for their relevance in sarcoidosis. Even though one of largest cohorts of beryllium-exposed persons was analysed, no statistically relevant association between any SNP and CBD could be verified. Notably, some SNPs exhibit inverse OR for beryllium sensitization and CBD with nominally statistical significance, which allows hypothesizing about pathophysiological role of genes for the disease triggering and development.

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.

O4D.1 Longitudinal analysis of incidence of beryllium sensitization in a us nuclear workforce

The goal of this study was to evaluate trends in incidence of beryllium sensitization (BeS) and the impact of exposure regulation in a US Department of Energy (DOE) nuclear worker cohort. The 1999 DOE final rule for Chronic Beryllium Disease Prevention Program was established to accomplish three goals: reduce the number of workers currently exposed to beryllium; minimize exposures and the potential for exposure; and establish medical surveillance requirements to ensure early detection of disease. While the impact of this rule has been evaluated through observational reports, with decreases in exposure and reported cases, there have been no published studies assessing whether exposure reduction measures result in the prevention of BeS.MethodsWe examined the incidence of beryllium sensitization in a cohort of 6915 workers with almost 29,000 BeLPT results obtained between 1994–2018. All workers were employed at a single DOE nuclear site that implemented the DOE beryllium rule between 1999–2002. Workers were classified as BeS when they met one of the following definitions: two abnormal blood BeLPT results, one abnormal and one borderline blood BeLPT result, three borderline blood BeLPT results, or one abnormal lung lavage BeLPT result. Descriptive statistics, longitudinal analyses, and correlation analyses were utilized to evaluate the trends in incidence before and after implementation of the beryllium rule.ResultsResults indicated a general decrease in exposure and BeS incidence rates, though there are some years with notable increases presumably due to increased clean-up activity, where construction and decommissioning workers had opportunity for exposure from legacy beryllium operation materials that were not part of normal current production activity.ConclusionThese findings provide support for the hypothesis that the DOE Beryllium Rule helps prevent beryllium sensitization. Future research will more precisely assess the relationship between beryllium exposure levels and beryllium incidence over time.