earlier diagnosis of CBD and has changed the clinical spectrum of CBD. This section reviews the recent epidemiologic literature on BeS and CBD and their clinical presentation, diagnosis, and management.

Epidemiologic Literature

CBD was first reported in the United States in the early 1940s by Van Ordstrand et al. (1943), Kress and Crispell (1944), and Hardy and Tabershaw (1946). Cases were observed in industrial plants that were refining and manufacturing beryllium metal and beryllium alloys and in plants manufacturing fluorescent light bulbs. By 1948, the known cases totaled more than 400, and the basic clinical features of the disease were understood. It was established that the risk of disease among beryllium workers rose with the intensity of airborne exposure and that risk varied with the physicochemical properties of the beryllium exposure (Machle et al. 1948; see Chapter 2 for more information). From the late 1940s into the 1960s, there were also outbreaks of CBD caused by air pollution around beryllium refineries in Ohio and Pennsylvania and outbreaks in family members of beryllium-factory workers, presumably caused by contaminated clothing (Hardy 1980). Although there was a clear relationship between the air concentration of beryllium and the risk of CBD in areas close to the factories, the disease rates outside the plant were higher than expected (Eisenbud et al. 1949; Lieben and Metzner 1959).

The risk of CBD in workers exposed during the 1940s and 1950s has been estimated to be 1-10% (Eisenbud and Lisson 1983), although there is considerable uncertainty because most of the studies in that era did not use well-defined cohorts or have adequate followup.

Sterner and Eisenbud (1951) first proposed an immunologic mechanism of CBD in 1951. Their evidence was largely circumstantial, but their inference was correct. They based their hypothesis on several pieces of evidence: the highly variable incidence in different groups of workers, the surprisingly high risk in neighborhoods whose exposures appeared to be low, the sometimes rapid onset of disease after exposure, and the failure to observe an association between the amount of beryllium in lung autopsy specimens and the extent of lung damage.

From the 1940s through the 1960s, the Atomic Energy Commission (AEC) was the primary user of beryllium in the U.S. economy. In 1949, AEC’s occupational hygienists recommended an air standard of 2 μg/m3 as an 8-h time-weighted average and a peak standard of 25 μg/m3 (Eisenbud 1982). Before the widespread application of the BeLPT, it appeared that strict adherence to those standards might adequately protect workers from CBD. However, it is now clear that CBD occurs in factories that have beryllium aerosol concentrations consistently below 2 μg/m3 (Kreiss et al. 2007).

The development of the BeLPT changed case-finding tools used in CBD epidemiology studies from chest radiographs and spirometry to the identification of BeS with a blood test, followed up with biopsy as well as clinical examination. This change created a fundamental non-comparability in the clinical and epidemiology literature pre- and post-BeLPT development, which (along with reduced exposures) has been associated with identification of clinically milder cases of CBD compared with the older clinical and epidemiologic literature. There appears to be a consensus in the field that a case series of CBD identified in exposed workers by BeLPT and confirmed with biopsy provides more specificity in diagnosis compared with tools such as chest radiographs and spirometry. Unfortunately, there are no studies that formally document this impression. For this reason, in its review of the epidemiologic evidence, the committee decided to focus primarily on the epidemiologic studies of CBD that include the use of the BeLPT. The committee took into account the results of the older epidemiology studies along with clinical studies and case series describing clinically diagnosed CBD in the pre-BeLPT era to inform other sections of this chapter (see sections on “Presentation, Diagnosis and Testing of CBD” and “Natural History and Management”).

In a recent review, Kreiss et al. (2007) summarized 12 studies (with overlapping populations) in which CBD prevalence was assessed cross-sectionally and ranged from 0.1% to nearly 8% (Table 3-1). Those data reflect exposures to workers decades after the recognition of the disease and indicate that many workers are still being exposed to concentrations of beryllium that put them at risk. The high

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