The primary finding of this descriptive study of beryllium-exposed workers from a research and development facility of the U.S. nuclear weapons industry is that the rate of beryllium sensitization is low (3%). In general, the workers screened for beryllium sensitization from this facility were exposed to only low levels of beryllium. The proportion with CBD among the sensitized individuals is also relatively low (10% to 12%) compared with workers in high-risk production operations such as beryllium machining or ceramics manufacturing. Furthermore, among the individuals with confirmed or probable CBD, there were no cases of disease severe enough to require immunosuppressive therapy.
Several other studies of U.S. workers in the nuclear weapons industry have reported low rates of beryllium sensitization (). A study by Welch et al8
of 3842 current and former construction workers at three DOE facilities (Hanford Nuclear Reservation, Oak Ridge Reservation, and the Savannah River Site) who participated in medical screening for beryllium sensitization showed that 53 (1.4%) of these workers had two positive BeLPTs; five workers were diagnosed to have CBD. Stange et al14
studied current and former workers at the Rocky Flats DOE facility, a nuclear weapons production plant with more workers potentially exposed to beryllium. Of the 5173 individuals from Rocky Flats who had BeLPTs done, 154 (3%) were sensitized (based on two positive BeLPTs) and 81 (1.6%) were diagnosed to have CBD.
Comparison of Beryllium Sensitization and CBD Rates At Several DOE Nuclear Facilities
The highest prevalence of BeS was among machinists (11.4%), but other groups of workers thought to have lower exposures such as custodial workers also had some increase in risk (5.6% prevalence of BeS). We compared data on area concentra-tions of beryllium from Rocky Flats and LLNL as a rough guide to relative differences in potential exposures of workers to beryllium between the two facilities ( and on-line supplement
). It is intriguing that while area concentrations at Rocky Flats were many times greater than at LLNL, the prevalence of beryllium sensitization is similar; however, the prevalence of CBD is approximately five times greater at Rocky Flats.
Within the LLNL population that likely had relatively lower exposures to beryllium than occurred at Rocky Flats, there was an inverse exposure-response gradient for progression from BeS to CBD based on job classification. None of the more highly exposed machinists at LLNL had evidence of CBD, whereas 38% of sensitized employees with low occupational exposure risk did progress. The higher percentage of CBD cases in the lower exposure category does not seem to be due to longer duration of exposure, as the mean work tenure of the five cases in this category, 16 years, is close to the overall mean of 18 years, and the mean latency of the five cases, 28 years, is close to the overall mean of 32 years. Unfortunately, personal beryllium exposure data from either monitoring or model estimates were not available for the workers we evaluated.
Why a positive BeLPT has a lower positive predictive value for CBD at LLNL and Hanford than at Rocky Flats and why sensitized workers with low exposure to beryllium at LLNL were more likely to have CBD than workers with moderate or high exposure are questions that remain to be answered. Clear exposure-response relationships among DOE workers with BeS are not apparent from the existing literature. Further investigation of the exposure-response relationships for both BeS and CBD is needed, especially for DOE-screened populations with relatively low-level exposures.
A study of 2221 workers involved in the cleanup of a former DOE nuclear weapons production facility that manufactured beryllium-containing weapon parts (presumably Rocky Flats) by Sackett et al19
showed that 19 (0.8%) were beryllium-sensitized based on two or more abnormal BeLPTs. These results taken together and extended by those we report here suggest that, in general, there is a relatively low risk of beryllium sensitization and CBD among workers in current or former nuclear weapons facilities and associated national weapons research laboratories, although some groups, such as production machinists, have much higher risk.
A diagnostic issue that our data touch on is the sensitivity of the BAL BeLPT, which has been suggested as being more sensitive than the peripheral blood BeLPT for predicting the presence of CBD.3,4
We report here that in three out of four cases of CBD for which a BAL BeLPT was performed, the test did not show abnormal lymphocyte proliferation to beryllium. In all three of the cases for which the BAL BeLPT was negative, two peripheral blood BeLPTs were positive. Although this sample of cases is too small to properly assess the sensitivity of the BAL BeLPT, our results do suggest that it might not be that sensitive for the diagnosis of CBD. The test can be helpful in the diagnosis of CBD, however, if biopsied lung tissue shows no evidence of granulomatous inflammation and when combined with results of other tests ().
Another clinical decision for which our data have relevance is when to perform bronchoscopy for the diagnosis of CBD. Because of the low prevalence of CBD among LLNL workers with beryllium sensitization as well as the lack of progression to clinically severe disease among those workers who have been diagnosed to have CBD, we have become more comfortable with annual medical follow-up of asymptomatic beryllium-sensitized workers with normal baseline pulmonary function tests and chest imaging instead of early bronchoscopy. It would be helpful if future research could provide more definitive evidence on which to base the important decision for a beryllium-sensitized patient about whether or not bronchoscopy with transbronchial biopsies should be performed. Because the procedure is invasive and carries serious risk, the decision ought to be based on evidence.
In conclusion, aggressive evaluation of beryllium-sensitized workers using bronchoscopy for multiple transbronchial biopsies of lung tissue as soon as two BeLPTs are positive may be warranted in some cases. However, in populations that have low rates of CBD among the sensitized and lack of progression to severe disease among those with CBD, noninvasive longitudinal follow up may be preferable. With the current state of knowledge, bronchoscopy might best be reserved for individuals with progressive symptoms, decrements in pulmonary function, or chest imaging findings.