Multisystemic Beryllium Disease: An Exceptional Case Revealed by a Urinary Tract Granulomatosis.

Chronic beryllium disease (CBD), or berylliosis, is an interstitial lung disease caused by the chronic inhalation of finely particulate beryllium, frequently mistaken for sarcoidosis. It is rarely associated with skin nodular lesions, asymptomatic granulomatous hepatitis or calcium nephrolithiasis. To date, it has never been reported as a diffused multi-organ granulomatous disease. A 60-year-old Pakistani man, a former excavation worker with ancient history of suspected sarcoidosis, underwent a left nephroureterectomy for suspected papillary kidney carcinoma. The histopathological analysis showed a benign non-necrotic granulomatous infiltration of the renal pelvis and ureter. Six months later, he suffered from two consecutive episodes of acute kidney failure. Bladder biopsies found similar noncaseous granulomatosis and kidney biopsies showed interstitial nephritis. Known for suspected asthma, sleep apnea, and usual interstitial pneumonia, the patient would regularly consult for episodes of pyrexia, chills, nocturnal coughing, and wheezing. As kidney function gradually worsened, he ultimately started hemodialysis and was transferred to our facility. A positive blood beryllium lymphocyte proliferation test confirmed the diagnosis of CBD. This original report is the first description of multi-organ berylliosis with diffused urothelial granulomatosis and pseudo-tumor. The patient's pulmonary disease is minimal compared with renal and urinary tract involvement, eventually responsible for end-stage kidney disease. Berylliosis usually responds to glucocorticoids. This case report highlights the importance of evoking the diagnosis of CBD in the presence of any granulomatosis, even extra-thoracic, especially if associated with pulmonary symptoms, however atypical.

Beryllium disease among construction trade workers at Department of Energy nuclear sites: A follow-up.

BACKGROUND: Construction workers at U.S. Department of Energy (DOE) nuclear weapons facilities are screened to identify DOE-related occupational illnesses, including beryllium sensitization (BeS) and chronic beryllium disease (CBD). The study objectives were to estimate beryllium disease risks and the CBD claims acceptance rate in the energy workers' benefits program. METHODS: Workers diagnosed with BeS via beryllium lymphocyte proliferation test (BeLPT) included in screening examinations were interviewed about subsequent diagnosis of CBD. We estimated the proportion who developed CBD based on the ratio of CBD cases, based on self-reported compensation claim status, to all workers with BeS interviewed. We used stratified analyses to explore trends in disease frequency by age, race, sex, DOE employment duration, site, trade group, and cigarette smoking history. RESULTS: Between 1998 and 2020, 21,854 workers received a BeLPT; 262 (1.20%) had BeS (two abnormals or one abnormal plus one borderline test); 212 (0.97%) had a single abnormal BeLPT. Of 177 BeS workers interviewed, 35 (19.8%) reported an accepted CBD compensation claim. The claims acceptance rate among BeS workers increased with years of DOE employment, from 8.4% with <5 years to 33.3% for >25 or more years. Five of 68 interviewed workers with a single positive BeLPT reported CBD claim acceptance; an additional CBD case was confirmed by chart review (8.8%). CONCLUSIONS: Years of DOE work predict the risk of developing CBD among those sensitized and getting a claim for CBD accepted. Ongoing surveillance and increased awareness of the risk of beryllium exposure and CBD as an occupational disease among construction workers are needed.

[Sarcoidosis and berylliosis]. / Sarkoidose und Berylliose.

Sarcoidosis and berylliosis (chronic beryllium disease, CBD) are granulomatous diseases and are phenocopies which cannot be differentiated based on the clinical presentation. Whereas for sarcoidosis the eliciting agent is unknown, for berylliosis an exposure to beryllium (mostly as occupational exposure) can be confirmed that therefore induces a sensitization against beryllium. The diagnosis is generally made in patients with a typical clinical presentation, the histological proof of a non-necrotizing granuloma and the exclusion of other diseases causing granulomas. In most cases, granulomas can be detected in the lungs and/or (intrathoracic) lymph nodes. The proof of sensitization to beryllium for the differential diagnosis can be performed with a so-called beryllium lymphocyte proliferation test in peripheral mononuclear blood cells or cells from a bronchoalveolar lavage. The objectives of treatment are avoidance of functional organ impairment and symptom control. Immunosuppressive therapy (initially mostly with corticosteroids) and supportive measures can prove beneficial; however, in many cases clinical observation can be sufficient because of stable disease or spontaneous resolution. In addition, further beryllium exposure must be avoided, which mostly necessitates a change of the workplace.

Clinical and laboratory factors contributing to uninterpretable beryllium lymphocyte proliferation tests (BeLPT).

BACKGROUND: The beryllium lymphocyte proliferation test (BeLPT), has become the principal clinical test for detecting beryllium sensitization and chronic beryllium disease. Uninterpretable BeLPT results can occur in a small but significant proportion of tests from poor lymphocyte growth (PG) or over proliferation of lymphocytes (OP). The clinical and laboratory causes of uninterpretable results are not known. METHODS: BeLPT data from the US Department of Energy-supported Former Worker Screening Program were analyzed for a 10-year period. Drivers of uninterpretable BeLPTs were investigated using multivariable models and classification techniques. RESULTS: Three participant attributes were significantly associated with PG, while OP showed no significant associations. Serum lot for the lymphocyte growth medium accounted for 21% of the variation in PG and 16% in OP. CONCLUSION: Serum lots influence the likelihood of having uninterpretable BeLPT. To better understand uninterpretable results and possibly reduce their occurrence, additional laboratory-related factors should be addressed.

An official American Thoracic Society statement: diagnosis and management of beryllium sensitivity and chronic beryllium disease.

RATIONALE: Beryllium continues to have a wide range of industrial applications. Exposure to beryllium can lead to sensitization (BeS) and chronic beryllium disease (CBD). OBJECTIVES: The purpose of this statement is to increase awareness and knowledge about beryllium exposure, BeS, and CBD. METHODS: Evidence was identified by a search of MEDLINE. The committee then summarized the evidence, drew conclusions, and described their approach to diagnosis and management. MAIN RESULTS: The beryllium lymphocyte proliferation test is the cornerstone of both medical surveillance and the diagnosis of BeS and CBD. A confirmed abnormal beryllium lymphocyte proliferation test without evidence of lung disease is diagnostic of BeS. BeS with evidence of a granulomatous inflammatory response in the lung is diagnostic of CBD. The determinants of progression from BeS to CBD are uncertain, but higher exposures and the presence of a genetic variant in the HLA-DP ß chain appear to increase the risk. Periodic evaluation of affected individuals can detect disease progression (from BeS to CBD, or from mild CBD to more severe CBD). Corticosteroid therapy is typically administered when a patient with CBD exhibits evidence of significant lung function abnormality or decline. CONCLUSIONS: Medical surveillance in workplaces that use beryllium-containing materials can identify individuals with BeS and at-risk groups of workers, which can help prioritize efforts to reduce inhalational and dermal exposures.

Sarcoidosis and chronic beryllium disease: similarities and differences.

Chronic beryllium disease (CBD) is a granulomatous lung disease that may be pathologically and clinically indistinguishable from pulmonary sarcoidosis, except through use of immunologic testing, such as the beryllium lymphocyte proliferation test (BeLPT). Similar to sarcoidosis, the pulmonary manifestations of CBD are variable and overlap with other respiratory diseases. Definitive diagnosis of CBD is established by evidence of immune sensitization to beryllium and diagnostic bronchoscopy with bronchoalveolar lavage and transbronchial biopsy. However, the diagnosis of CBD can also be established on a medically probable basis in beryllium-exposed patients with consistent radiographic imaging and clinical course. Beryllium workers exposed too much higher levels of beryllium in the past demonstrated a much more fulminant disease than is usually seen today. Some extrapulmonary manifestations similar to sarcoidosis were noted in these historic cohorts, although with a narrower spectrum. Extrapulmonary manifestations of CBD are rare today. Since lung-predominant sarcoidosis can very closely resemble CBD, CBD is still misdiagnosed as sarcoidosis when current or past exposure to beryllium is not recognized and no BeLPT is obtained. This article describes the similarities and differences between CBD and sarcoidosis, including clinical and diagnostic features that can help physicians consider CBD in patients with apparent lung-predominant sarcoidosis.

Beryllium disease among construction trade workers at Department of Energy nuclear sites.

BACKGROUND: A medical surveillance program was developed to identify current and former construction workers at significant risk for beryllium related disease from work at the DOE nuclear weapons facilities, and to improve surveillance among beryllium exposed workers. METHODS: Medical examinations included a medical history and a beryllium blood lymphocyte proliferation test (BeLPT). Stratified and multivariate logistic regression analyses were used to explore the risk of disease by age, race, trade, and reported work in buildings where beryllium was used. After adjusting for covariates, the risk of BeS was significantly higher among boilermakers, roofers, and sheet metal workers, as suggested in the stratified analyses. Workers identified as sensitized to beryllium were interviewed to determine whether they had been subsequently diagnosed with chronic beryllium disease. RESULTS: Between 1998 and December 31, 2010 13,810 workers received a BeLPT through the BTMed program; 189 (1.4%) were sensitized to beryllium, and 28 reported that they had had a compensation claim accepted for CBD. CONCLUSIONS: These data on former construction workers gives us additional information about the predictive value of the blood BeLPT test for detection of CBD in populations with lower total lifetime exposures and more remote exposures than that experienced by current workers in beryllium machining operations. Through this surveillance program we have identified routes of exposures to beryllium and worked with DOE site personnel to identity and mitigate those exposures which still exist, as well as helping to focus attention on the risk for beryllium exposure among current demolition workers at these facilities.

Pneumoconioses.

Occupational lung diseases are caused or made worse by exposure to harmful substances in the work-place. "Pneumoconiosis" is the term used for the diseases associated with inhalation of mineral dusts. While many of these broad-spectrum substances may be encountered in the general environment, many occur in the work-place for greater amounts as a result of industrial processes; therefore, a range of lung reactions may occur as a result of work-place exposure. Physicians in metropolitan cities are likely to encounter pneumoconiosis for two reasons: (i) patients coming to seek medical help from geographic areas where pneumoconiosis is common, and (ii) pneumoconiosis caused by unregulated small-scale industries that are housed in poorly ventilated sheds within the city. A sound knowledge about the various pneumoconioses and a high index of suspicion are necessary in order to make a diagnosis. Identifying the disease is important not only for treatment of the individual case but also to recognise and prevent similar disease in co-workers.

Chest wall shrapnel-induced beryllium-sensitization and associated pulmonary disease.

Chronic beryllium disease (CBD) is an exposure-related granulomatous disease mimicking sarcoidosis. Beryllium exposure-associated disease occurs mainly via inhalation, but skin may also be a source of sensitization. A 65-year-old male with a history of war-related shrapnel wounds was initially diagnosed with pulmonary sarcoidosis. Twenty years later, the possibility of a metal-related etiology for the lung disease was raised. A beryllium lymphocyte proliferation test, elemental analysis of removed shrapnel, and genetic studies were consistent with a diagnosis of CBD. This case demonstrates that retained beryllium-containing foreign bodies can be linked to a pathophysiologic response in the lung consistent with CBD.

Systematic review: Progression of beryllium sensitization to chronic beryllium disease.

BACKGROUND: The relevance of beryllium sensitization testing for occupational health practice and prevention is unclear. AIMS: To analyse the natural course of beryllium sensitization and clarify the prognosis following cessation of exposure among sensitized workers. METHODS: An electronic literature search was conducted in PubMed, Embase, Toxline and Cochrane databases supplemented by a manual search. Data abstraction and study quality assessment with adapted guideline checklists were performed independently by three reviewers. Seven studies met the eligibility criteria and were included in the systematic review; however, six of the seven studies were of low methodological quality. RESULTS: A substantial (although not specifically quantifiable) proportion of beryllium-sensitized employees will develop chronic beryllium disease (CBD). To date, it is unknown if cessation of exposure in sensitized workers reduces the progression rate to CBD. CONCLUSIONS: To determine the utility of regular assessments for beryllium sensitization among exposed workers, there is a need for prospective studies. This should include detailed and continuous exposure monitoring, regular tests for beryllium sensitization and a thorough diagnostic evaluation of sensitized workers to confirm or exclude CBD.

SELDI-TOF derived serum biomarkers failed to differentiate between patients with beryllium sensitisation and patients with chronic beryllium disease.

BACKGROUND: People exposed to beryllium may develop beryllium sensitisation (BeS) and, in some cases, progress to chronic beryllium disease (CBD). OBJECTIVES: The objective of this study was to test the ability of proteomic technology to identify patterns of serum protein biomarkers that allow differentiation between BeS and CBD and thus remove the need for invasive bronchoscopic procedures. METHODS: Initially, SELDI-TOF methodology and analysis was performed on serum samples from 30 CBD and 31 BeS patients. RESULTS: This 'starter set' yielded two distinct biomarker pattern sets with eight candidate proteins. The first set differentiated between BeS and CBD with 83.3% sensitivity and 82.3% specificity, with 10-fold cross-validation of 75% and 79%, respectively. The second set of biomarkers yielded higher sensitivity (90.0%) and higher specificity (90.3%), with 10-fold cross-validation of 71.7% and 82.3%, respectively. Due to its greater sensitivity and specificity, the second set of biomarkers was used as the framework for differentiating between CBD and BeS in a second set of serum samples from 450 patients with BeS and CBD. When this larger set of samples was subjected to the biomarker framework in a blinded fashion, it yielded a sensitivity of 43.53% and a specificity of 38.93%. CONCLUSIONS: Due to these low sensitivity and specificity values, we have concluded that, currently, the unique set of SELDI-TOF derived biomarkers does not possess the qualities that would allow it to differentiate between a CBD patient and a BeS patient using serum protein biomarkers. Future refinements in sample collection or proteomic technology may be needed to improve biomarker discovery.

Search for chronic beryllium disease among sarcoidosis patients in Ontario, Canada.

Chronic beryllium disease (CBD) is clinically similar to other granulomatous diseases such as sarcoidosis. It is often misdiagnosed if a thorough occupational history is not taken. When appropriate, a beryllium lymphocyte proliferation tests (BeLPT) need to be performed. We aimed to search for CBD among currently diagnosed pulmonary sarcoidosis patients and to identify the occupations and exposures in Ontario leading to CBD. Questionnaire items included work history and details of possible exposure to beryllium. Participants who provided a history of previous work with metals underwent BeLPTs and an ELISPOT on the basis of having a higher pretest probability of CBD. Among 121 sarcoid patients enrolled, 87 (72%) reported no known previous metal dust or fume exposure, while 34 (28%) had metal exposure, including 17 (14%) with beryllium exposure at work or home. However, none of these 34 who underwent testing had positive test results. Self-reported exposure to beryllium or metals was relatively common in these patients with clinical sarcoidosis, but CBD was not confirmed using blood assays in this population.

Interpreting borderline BeLPT results.

BACKGROUND: The beryllium lymphocyte proliferation test (BeLPT) identifies persons sensitized to beryllium (BeS) and thus at risk for chronic beryllium disease (CBD). BeLPT test results are abnormal (AB), borderline (BL), or normal (NL). This manuscript addresses the predictive value and interpretation of BL BeLPT results. METHODS: The various three-result combinations that meet or exceed a nominal referral criteria of 1 AB + 1 BL are assessed with probability modeling and compared. RESULTS: At 2% prevalence, the three-result combinations that meet or exceed this referral criteria and associated probabilities of BeS are: (a) 1 AB + 1 BL + 1 NL (72%); (b) 3 BL (91%); (c) 2 AB + 1 NL (95%); (d) 1 AB + 2 BL (99%); (e) 2 AB + 1 BL (100%); and (f) 3 AB (100%). CONCLUSION: These results suggest that BL results are meaningful and that three BL results predict BeS across a broad range of population prevalences. An analysis of longitudinal BeLPT results and clinical findings from an actual surveillance program is warranted to confirm the model's predictions.

Risk of beryllium sensitization in a low-exposed former nuclear weapons cohort from the Cold War era.

BACKGROUND: The nuclear weapons industry has long been known as a source of beryllium exposure. METHODS: A total of 1,004 former workers from a nuclear weapons assembly site in the Midwest were screened for sensitization to beryllium (BeS). The screenings were part of the Department of Energy (DOE) Former Worker Program established in 1996. RESULTS: Twenty-three (2.3%) workers were found sensitized to beryllium and this prevalence was comparable to other DOE sites. Occasional, direct exposure to beryllium through machining and grinding of copper-beryllium (Cu-Be) 2% alloy tools was found to increase the risk of sensitization compared to background exposure (OR = 3.83; 95% CI: 1.04-14.03) with a statistically significant trend (P = 0.03) revealing that particular jobs are associated with sensitization. Exposure potential in this study was estimated based on job titles and not personal exposure information. CONCLUSIONS: These results confirm the need to screen workers using beryllium alloy tools in other industries and for consideration of altering work practices.

A Cluster of Beryllium Sensitization Traced to the Presence of Beryllium in Concrete Dust.

BACKGROUND: Chronic beryllium disease (CBD), a granulomatous disease with similarities to sarcoidosis, arises only in individuals exposed to beryllium. Inhaled beryllium can elicit a T-cell-dominated alveolitis leading nonnecrotizing granulomata. CBD can be distinguished from sarcoidosis by demonstrating beryllium sensitization in a lymphocyte proliferation test. RESEARCH QUESTION: Beryllium exposure usually occurs in an occupational setting. Because of the diagnosis of CBD in a patient without evident beryllium exposure, we performed a beryllium-lymphocyte proliferation test (BeLPT) among his work colleagues. STUDY DESIGN AND METHODS: This field study investigated a cohort of work colleagues without obvious beryllium exposure. Twenty-one of 30 individuals were assessed in our outpatient clinic for beryllium sensitization. Therefore, BeLPT was performed with freshly collected peripheral blood mononuclear cells. Data were extracted from clinical charts, including geographical data. Beryllium content in dust samples collected at the workplace was measured by graphite-furnace atomic absorption spectroscopy and was compared with samples from different areas of Germany. RESULTS: For the initial patient, the diagnosis of sarcoidosis was reclassified as CBD based on two positive BeLPT results. Assessment of his workplace did not identify a source of beryllium. However, BeLPTs performed on his workmates demonstrated beryllium sensitization in 5 of 21 individuals, suggesting a local beryllium source. Concrete dust obtained from the building yard, the workplace of the index patient, contained high amounts of beryllium (1138 ± 162 µg/kg), whereas dust from other localities (control samples) showed much lower beryllium content (range, 147 ± 18-452 ± 206 µg/kg). Notably, the control dust collected from different places all over Germany exhibit different beryllium concentrations. INTERPRETATION: We describe a cluster of beryllium-sensitized workers from an industry not related to beryllium caused by environmental exposure to beryllium-containing concrete dust, which exhibited markedly elevated beryllium content. Importantly, analyses of dust samples collected from different localities showed that they contain markedly different amounts of beryllium. Thus, besides workplace-related exposure, environmental factors also are capable of eliciting a beryllium sensitization.

Genomic biomarkers in chronic beryllium disease and sarcoidosis.

Background Previous gene expression studies have identified genes IFNγ, TNFα, RNase 3, CXCL9, and CD55 as potential biomarkers for sarcoidosis and/or chronic beryllium disease (CBD). We hypothesized that differential expression of these genes could function as diagnostic biomarkers for sarcoidosis and CBD, and prognostic biomarkers for sarcoidosis. Study Design/Methods We performed RT-qPCR on whole blood samples from CBD (n = 132), beryllium sensitized (BeS) (n = 109), and sarcoidosis (n = 99) cases and non-diseased controls (n = 97) to determine differential expression of target genes. We then performed logistic regression modeling and generated ROC curves to determine which genes could most accurately differentiate: 1) CBD versus sarcoidosis 2) CBD versus BeS 3) sarcoidosis versus controls 4) non-progressive versus progressive sarcoidosis. Results CD55 and TNFα were significantly upregulated, while CXCL9 was significantly downregulated in CBD compared to sarcoidosis (p < 0.05). The ROC curve from the logistic regression model demonstrated high discriminatory ability of the combination of CD55, TNFα, and CXCL9 to distinguish between CBD and sarcoidosis with an AUC of 0.98. CD55 and TNFα were significantly downregulated in sarcoidosis compared to controls (p < 0.05). The ROC curve from the model showed a reasonable discriminatory ability of CD55 and TNFα to distinguish between sarcoidosis and controls with an AUC of 0.86. There was no combination of genes that could accurately differentiate between CBD and BeS or sarcoidosis phenotypes. Interpretation CD55, TNFα and CXCL9 expression levels can accurately differentiate between CBD and sarcoidosis, while CD55 and TNFα expression levels can accurately differentiate sarcoidosis and controls.

[Management of occupational health for adverse health effects of beryllium and its compounds in workplaces - Recent trends and issues in Japan].

OBJECTIVES: Beryllium is primarily used in its metallic form, in alloys, or in beryllium oxide ceramics. Its physical and mechanical properties make it useful for many applications across a range of industries. Because beryllium is recognized as a sensitizing and carcinogenic agent, the management of occupational health for workers who may be occupationally exposed to beryllium has long been an important issue in the world. Under these circumstances, the U.S. Occupational Safety and Health Administration (OSHA) had published a rule in January 2017, to prevent the development of chronic beryllium disease and lung cancer. This rule strengthens the regulations governing the use of beryllium and its compounds. With the announcement of the OSHA rule in January 2017, the purpose of this study is to gain insight into the health problems and industrial hygiene associated with the use of beryllium and share the issues related to the management of occupational health for persons working with beryllium in Japan. METHODS: We collected information regarding the beryllium industry, beryllium exposure, beryllium-induced health disorders, OSHA rule of January 2017, and regulations for beryllium use in Japan. After reviewing them, we discussed the issues concerning occupational health management of workers exposed to beryllium in Japan. RESULTS: It has been reconfirmed that in recent years, the most serious health problem due to beryllium exposure is chronic beryllium disease caused by beryllium sensitization. Management of occupational health that emphasizes reduction of beryllium sensitization and early detection of beryllium-sensitized workers is important. CONCLUSIONS: It was suggested that the following should be considered as the issues of management of occupational health of workers exposed to beryllium in Japan: (1) Collect epidemiologic data on health hazards from beryllium exposure in Japan. (2) Review the diagnostic items of special medical check-ups. (3) Review the definition of beryllium and its compounds in the Ordinance on Prevention of Hazards due to Specified Chemical Substances.

Non-invasive diagnosis of chronic beryllium disease in workers exposed to hazardous dust in Israel.

OBJECTIVES: Chronic beryllium disease (CBD) is caused by prolonged occupational exposure to beryllium and is characterised by various clinical presentations, mostly pulmonary. The inflammatory process involves non-caseous granulomas and proliferation of CD4+ cells. CBD is diagnosed by lung biopsy showing tissue granuloma formation, and by the beryllium lymphocyte proliferation test (BeLPT) for past exposure and sensitisation to beryllium. The induced sputum (IS) technique was developed for diagnosing asthma, chronic obstructive pulmonary disease and interstitial lung diseases. A CD4/CD8 ratio >2.5 in T cells from IS is a positive result for granulomatous lung diseases. We previously revealed that dental technicians are exposed to excessive levels of beryllium. The efficacy of IS (CD4/CD8 >2.5) and BeLPT in diagnosing CBD in 17 workplaces where beryllium was present was evaluated. METHODS: All consecutive patients with a clinical suspicion of CBD referred to our institution for diagnosis and management were enrolled. Results of the gold standard lung biopsy with BeLPT were compared to the non-invasive IS+BeLPT. Kappa and McNemar tests evaluated agreement levels. Correlations between demographic and clinical parameters and a confirmed diagnosis of CBD were analysed. RESULTS: The two approaches were compared in 57 of 98 subjects. There was a high level of agreement (kappa 0.920) between IS+BeLPT and biopsy+BeLPT. IS+BeLPT had a specificity of 97.3% and sensitivity of 87.5%. 21 of 87 exposed workers (24%) had CBD, of whom 12 were dental technicians (p=0.044 dental technicians versus all other occupations). CONCLUSIONS: This study demonstrated that the CD4/CD8 ratio in IS together with positive/negative BeLPT findings can be used in diagnosing CBD.

Long-term follow-up of beryllium sensitized workers from a single employer.

BACKGROUND: Up to 12% of beryllium-exposed American workers would test positive on beryllium lymphocyte proliferation test (BeLPT) screening, but the implications of sensitization remain uncertain. METHODS: Seventy two current and former employees of a beryllium manufacturer, including 22 with pathologic changes of chronic beryllium disease (CBD), and 50 without, with a confirmed positive test were followed-up for 7.4 +/-3.1 years. RESULTS: Beyond predicted effects of aging, flow rates and lung volumes changed little from baseline, while DLCO dropped 17.4% of predicted on average. Despite this group decline, only 8 subjects (11.1%) demonstrated physiologic or radiologic abnormalities typical of CBD. Other than baseline status, no clinical or laboratory feature distinguished those who clinically manifested CBD at follow-up from those who did not. CONCLUSIONS: The clinical outlook remains favorable for beryllium-sensitized individuals over the first 5-12 years. However, declines in DLCO may presage further and more serious clinical manifestations in the future. These conclusions are tempered by the possibility of selection bias and other study limitations.

Prevalence of beryllium sensitization among aluminium smelter workers.

BACKGROUND: Beryllium exposure occurs in aluminium smelters from natural contamination of bauxite, the principal source of aluminium. AIMS: To characterize beryllium exposure in aluminium smelters and determine the prevalence rate of beryllium sensitization (BeS) among aluminium smelter workers. METHODS: A population of 3185 workers from nine aluminium smelters owned by four different aluminium-producing companies were determined to have significant beryllium exposure. Of these, 1932 workers participated in medical surveillance programmes that included the serum beryllium lymphocyte proliferation test (BeLPT), confirmation of sensitization by at least two abnormal BeLPT test results and further evaluation for chronic beryllium disease in workers with BeS. RESULTS: Personal beryllium samples obtained from the nine aluminium smelters showed a range of <0.01-13.00 µg/m(3) time-weighted average with an arithmetic mean of 0.25 µg/m(3) and geometric mean of 0.06 µg/m(3). Nine workers were diagnosed with BeS (prevalence rate of 0.47%, 95% confidence interval = 0.21-0.88%). CONCLUSIONS: BeS can occur in aluminium smelter workers through natural beryllium contamination of the bauxite and further concentration during the refining and smelting processes. Exposure levels to beryllium observed in aluminium smelters are similar to those seen in other industries that utilize beryllium. However, compared with beryllium-exposed workers in other industries, the rate of BeS among aluminium smelter workers appears lower. This lower observed rate may be related to a more soluble form of beryllium found in the aluminium smelting work environment as well as the consistent use of respiratory protection.