Simultaneous testing of immunological sensitization to multiple antigens in sarcoidosis reveals an association with inorganic antigens specifically related to a fibrotic phenotype.

Organic and inorganic antigens were studied simultaneously in the same cohort of sarcoidosis patients to investigate whether correlations between clinical characteristics and immunological sensitization could reveal new phenotypes. Sensitization to antigens of mycobacteria, Propionibacterium acnes catalase and vimentin was investigated in 201 sarcoidosis and 51 obstructive sleep apnoea patients, serving as control group. Sensitization to aluminium, beryllium, silica and zirconium was also studied in 105 of the sarcoidosis patients and in 24 of the controls. A significantly higher percentage of sarcoidosis patients (27·6%) than controls (4·2%) had an immunological response to metals or silica (P = 0·014). A higher percentage of these sarcoidosis patients showed fibrosis on chest X-ray 5 years after the diagnosis (69·2 versus 30·3%, P = 0·016). No significant differences in mycobacterial or vimentin enzyme-linked immunospot (ELISPOT) assay results were observed between sarcoidosis and control patients. A significantly lower percentage of sarcoidosis patients (3·5%) than control patients (15·7%) had a positive ELISPOT for P. acnes catalase (P = 0·003). However, sarcoidosis patients sensitized to P. acnes catalase were more likely to have skin involvement, while sarcoidosis patients sensitized to mycobacterial antigens were more likely to have cardiac involvement. Our study suggests a more prominent role for inorganic triggers in sarcoidosis pathogenesis than previously thought. Immunological sensitization to inorganic antigens was associated with development of fibrotic sarcoidosis. No association was found between sensitization to bacterial antigens or vimentin and sarcoidosis in Dutch patients. However, our data suggest that trigger-related phenotypes can exist in the heterogeneous population of sarcoidosis patients.

Serum and urinary concentrations of arsenic, beryllium, cadmium and lead after an aerobic training period of six months in aerobic athletes and sedentary people.

AIM: The aim of the present study was to evaluate the possible effect of a period of 6 months of aerobic physical training on serum and urinary concentrations of arsenic (As), beryllium (Be), cadmium (Cd) and lead (Pb), potentially toxic minerals. METHODS: Twenty-four well-trained, long distance runners (AG), were recruited at the start of their training period. They had been performing training regularly for the previous 2 years, recording an average volume of 120 km per week of rigorous aerobic exercise aimed at high-level competitions (1500 and 5000 m race modalities). Twenty-six untrained, sedentary participants constituted the control group (CG). All participants had been living in the same geographic area for at least 2 years before the start of the survey. Serum and urine samples were obtained from each participant at the beginning and at the end of the 6 months of the training program. The values of each mineral were determined by inductively coupled plasma mass spectrometry (ICP-MS). Additionally, the daily intake of each mineral was evaluated at both moments in time. RESULTS: The daily concentrations of trace elements in the diet were similar at the start and the end of the training period without differences between groups. In serum, significant differences between groups were observed in As, Cd and Pb (p < 0.05). Attending to time effects, a significant difference was obtained in Pb (p < 0.05). In urine, significant differences between groups were obtained in all minerals (p < 0.05). According to training period, significant differences were observed in As, Be and Pb (p < 0.05). Finally, the group x time interaction revealed significant differences in As and Be (p < 0.05). CONCLUSIONS: Aerobic training may constitute a possibly effective method for increasing the elimination of Cd and Pb potentially toxic minerals from the body, especially among highly trained individuals.

New insight in beryllium toxicity excluding exposure to beryllium-containing dust: accumulation patterns, target organs, and elimination.

There is much contradiction between different experimental studies on beryllium (Be) toxicity. The majority of studies focus on occupational pathologies, caused by the exposure to Be dust. However, Be pollution may affect wide population groups through other exposure routes. The discrepancies between experimental studies may be attributed to the lack of adequate Be toxicity model since conventional administration routes are hampered by high acidity and low solubility of Be compounds. This study was aimed to develop a novel way to implement Be toxicity avoiding side effects, related to high acidity or low solubility of Be salts. Intraperitoneal injection of Be-glycine composition (containing BeSO4, glycine, purified water, pH adjusted to 5.5 with NaOH) was tested in the dose range 238-7622 µmol Be kg-1 (body weight, b/w) in full-grown Wistar male rats. The model provided reliable uptake of Be from the peritoneum into general circulation for at least 48 h. LD50 was found to be 687 µmol Be kg-1 (b/w). The established LD50 value differed from previous data on gastrointestinal, intramuscular or intravenous administration of Be compounds. The liver was found to act as a primary elimination route for Be and related to the highest Be content in the animal. However, it had no signs of morphological damage, which was observed only in the testes (deterioration of germinal epithelium). At the same time, the lungs, stated as a primary target tissue for Be in the models of chronic beryllium disease, did not show strong Be accumulation nor morphological changes. Survived animals showed behavioral changes, including increased motor activity and aggressive reactions in some cases, and complete spasticity in other. The obtained data show the applicability of the established modeling protocol and testified for the independence of chronic beryllium disease on Be2+ ion toxicity per se.

Sodium bicarbonate therapy for critically ill patients with metabolic acidosis: A scoping and a systematic review.

PURPOSE: We aimed to assess the biochemical and physiological effects, clinical efficacy, and safety, of intravenous NaHCO3 therapy in critically ill patients with acute metabolic acidosis. METHODS: We conducted a scoping review concerning the biochemical and physiological effects of NaHCO3 (PART A), and a systematic review regarding clinical efficacy (PART B). We searched MEDLINE in Part A and MEDLINE, EMBASE, Cochrane, the National Institute of Health Clinical Trials Register, and the WHOICTRP for randomised controlled trials in Part B. RESULTS: Twelve studies in Part A and two trials in Part B fulfilled the eligibility criteria. Intravenous NaHCO3 increased blood pH, base excess, serum bicarbonate, sodium, and PaCO2 during and after administration and decreased anion gap and potassium value. For clinical efficacy, only one study contributed to the effect estimate. The risk ratio (RR) for all-cause mortality was 0.83 (95% confidence interval, 0.68 to 1.02), and the risk of hypocalcaemia was increased in the bicarbonate group (RR 1.65, 95% confidence interval 1.09 to 2.50). There were inadequate data on hemodynamic indices. CONCLUSIONS: Given the lack of data on the effects of intravenous NaHCO3 therapy to support its clinical use and the frequency of bicarbonate therapy, a program of investigation appears justified.

Influence of an exercise until exhaustion in serum and urinary concentrations of toxic minerals among professional athletes, a preliminary approach.

The aim of the present survey was to determine differences in the serum and urinary concentrations of several toxic trace elements (As, Be, Cd, Cs and Pb) between long distance runners and non-sportsmen living in the same area of Extremadura (Spain) in basal conditions as well as after the performance of a maximal effort test until exhaustion. 21 Spanish national long-distance runners were recruited before the start of their training season and 26 untrained students. All of them had similar ages. The effort test consisted in running on a treadmill incrementally in stages, until exhaustion. Serum and urine analysis of trace metals was performed by inductively coupled plasma mass spectrometry (ICP-MS). In the statistics the urine and blood basal concentrations was analyzed first using Student t test. Then the differences between the pre and post-test values were analyzed using Wilcoxon test. The serum concentrations of Be (p < 0.001), Cd (p < 0.01), Cs (p < 0.001) and Pb (p < 0.001) were higher in the athletes than the control groups in basal conditions. In relation to the exercise, the results showed that there were lower serum concentrations of Be, Cd and Pb after the test, but without statistically significance, in both groups. Cs (p < 0.001) concentrations were statistically lower after the exercise tests in both groups, but if the parameters were corrected in relation to hematocrit and hemoglobin concentrations the differences were significant only among the athletes. In urine, the concentrations of Be (p < 0.001) and Cd (p < 0.01) were higher among athletes than among controls, being the opposite case for urinary Pb values. In relation to the exercise-induced effect of the test, the results showed that among controls only Cd values were modified, but if creatinine corrections are applied this difference does not reach statistical significance. However, sportsmen suffered a diminution in Be values, that can be observed only if urine values are corrected. Also, an increase in Cd, both in corrected and normal values, was observed, fact that occurred also in the case of Cs, but only if urinary values are corrected. It can be concluded that an incremental exercise to exhaustion among elite athletes of long distance modalities can produce changes in serum and urinary concentrations of toxic trace elements which may reflect an adaptive mechanism to prevent toxicity, and which could be an interesting outcome for physicians in the treatment and prevention of toxic situations.

Effect of long-term aerobic, anaerobic and aerobic-anaerobic physical training in seric toxic minerals concentrations.

BACKGROUND: Many substances poured out from industries can be toxic to humans and can impair physical performance. Besides, physical training may modify the body concentrations of these substances as a result of physiological adaptations. OBJECTIVES: The aim of the study was to determine if different modalities of exercise might affect serum concentrations of toxic trace elements in sportsmen. METHODS: 80 Spanish national sportsmen were recruited before the start of their training period. All the athletes had been training regularly for the previous two years with a rigorous training target at high-level competition. 31 sedentary participants from the same geographic area formed the control group. Serum arsenic, beryllium, cadmium, cesium and lead samples were analyzed with an ICP-MS. RESULTS: Serum concentrations were higher among the sportsmen group than among the control group, being highly significant in cases of Be from 0.043±0.019 to 0.074±0.029µg/L, Cs from 0.693±0.305 to 1.358±0.569µg/L and Pb from 0.162±0.171 to 2.375±1.699µg/L; and significant in the case of Cd from 0.046±0.027 to 0.067±0.059µg/L. However, if they were separated according to different sport modalities, it was found that, although they had higher concentrations than controls, there were elements that changed their concentrations in relation to the metabolic type of activity performed. CONCLUSIONS: In some cases physical exercise induces favorable adaptations to avoid environmental pollution damage. Endurance training (65-75% VO2max) can be considered the most effective exercise to prevent toxicity effects. However, integral-matrixes analysis are required in further research to overcome some controversial behaviors of some elements.

Concentrations of Trace Elements in Hemodialysis Patients: A Prospective Cohort Study.

BACKGROUND: Low concentrations and excessive concentrations of trace elements have been commonly reported in hemodialysis patients, but available studies have several important limitations. STUDY DESIGN: Random sample of patients drawn from a prospective cohort. SETTING & PARTICIPANTS: 198 incident hemodialysis patients treated in 3 Canadian centers. MEASUREMENTS: We used mass spectrometry to measure plasma concentrations of the 25 elements at baseline, 6 months, 1 year, and 2 years following enrollment in the cohort. We focused on low concentrations of zinc, selenium, and manganese and excessive concentrations of lead, arsenic, and mercury; low and excessive concentrations of the other 19 trace elements were treated as exploratory analyses. Low and excessive concentrations were based on the 5th and 95th percentile plasma concentrations from healthy reference populations. RESULTS: At all 4 occasions, low zinc, selenium, and manganese concentrations were uncommon in study participants (≤5.1%, ≤1.8%, and ≤0.9% for zinc, selenium, and manganese, respectively) and a substantial proportion of participants had concentrations that exceeded the 95th percentile (≥65.2%, ≥74.2%, and ≥19.7%, respectively). Almost all participants had plasma lead concentrations above the 95th percentile at all time points. The proportion of participants with plasma arsenic concentrations exceeding the 95th percentile was relatively constant over time (9.1%-9.8%); the proportion with plasma mercury concentrations that exceeded the 95th percentile varied between 15.2% and 29.3%. Low arsenic, platinum, tungsten, and beryllium concentrations were common (>50%), as were excessive cobalt, manganese, zinc, vanadium, cadmium, selenium, barium, antimony, nickel, molybdenum, lead, and chromium concentrations. CONCLUSIONS: There was no evidence that low zinc, selenium, or manganese concentrations exist in most contemporary Canadian hemodialysis patients. Some patients have excessive plasma arsenic and mercury concentrations, and excessive lead concentrations were common. These findings require further investigation.

[Distribution of rubidium, cesium, beryllium, strontium, and barium in blood and urine in general Chinese population].

OBJECTIVE: To investigate the distribution of rubidium (Rb), cesium (Cs), beryllium (Be), strontium (Sr), and barium (Ba) in blood and urine in general Chinese population. METHODS: A total of 18 120 subjects aged 6~60 years were enrolled from 24 regions in 8 provinces in Eastern, Central, and Western China from 2009 to 2010 based on the method of cluster random sampling. Questionnaire survey was conducted to collect the data on living environment and health status. Blood and urine samples were collected from these subjects, and the levels of Rb, Cs, Be, Sr, and Ba in these samples were determined by inductively coupled plasma mass spectrometry. The distribution of these elements in blood and urine in male or female subjects living in different regions was analyzed statistically. RESULTS: In the general Chinese population, the concentration of Be in the whole blood was below the detection limit (0.06 µg/L); the geometric mean (GM) of Ba in the whole blood was below the detection limit (0.45 µg/L), with the 95th percentile (P95)of 1.37 µg/L; the GMs (95% CI)of Rb, Cs, and Sr in the whole blood were 2 374(2 357~2 392) µg/L, 2.01 (1.98~2.05) µg/L, and 23.5 (23.3~23.7) µg/L, respectively; in males and females, the GMs (95%CI)of blood Rb, Cs, and Sr were 2 506 (2 478~2 533) µg/L and 2 248 (2 227~2 270) µg/L, 1.88 (1.83~1.94) µg/L and 2.16 (2.11~2.20) µg/L, and 23.4 (23.1~23.7) µg/L and 23.6 (23.3~23.9) µg/L, respectively(P<0.01, P>0.05, and P>0.05). In the general Chinese population, the GM of urine Be was below the detection limit (0.06 µg/L), while the GMs (95%CI)of urine Rb, Cs, Sr, and Ba were 854 (836~873) µg/L, 3.65 (3.56~3.74) µg/L, 39.5 (38.4~40.6) µg/L, and 1.10 (1.07~1.12) µg/L, respectively; in males and females, the GMs (95%CI)of urine Rb, Cs, Sr, and Ba were 876 (849~904) µg/L and 832 (807~858) µg/L, 3.83 (3.70~3.96) µg/L and 3.47 (3.35~3.60) µg/L, 42.5 (40.9~44.2) µg/L and 36.6 (35.1~38.0) µg/L, and 1.15 (1.12~1.19) µg/L and 1.04 (1.01~1.07) µg/L, respectively (all P< 0.01). Correlation analyses showed that there were weak correlations between blood Rb and urine Rb (r=0.197)and between blood Sr and urine Sr (r=0.180), but a good correlation between blood Cs and urine Cs (r=0.487). CONCLUSION: The levels of Rb, Cs, Be, Sr, and Ba in the general Chinese population are similar to those reported in other countries, and there is a significant difference in the concentration of each element among the populations living in different regions, as well as significant differences in blood Rb, urine Rb, urine Cs, urine Sr, and urine Ba between males and females.

Biomonitoring of 20 trace elements in blood and urine of occupationally exposed workers by sector field inductively coupled plasma mass spectrometry.

A sector field inductively coupled plasma mass spectrometry method for the determination of Ag, Al, As, Ba, Be, Cd, Co, Cr, Cs, Cu, Fe, Mn, Ni, Pb, Se, Sr, Tl, U, V and Zn in whole blood and urine was designed. Microwave-assisted digestion with concentrated nitric acid was used for blood samples. Urine samples were analyzed after 1/50 (v/v) dilution with 5% (v/v) nitric acid. For beryllium the necessity of medium resolution mode (R=4000) was shown. Method validation was performed using blood and urine reference materials and by analyzing of spiked samples. For the designed method relative standard deviation (RSD) for the concentration range 0.01-1.0 µg/L was 5-10%. RSD did not exceed 3% when trace elements concentrations were above 1.0 µg/L. Method detection limits (3σ): Ag 0.7 ng/L, Al 16 ng/L, As 3.4 ng/L, Ba 0.02 ng/L, Be 1.5 ng/L, Cd 7.7 ng/L, Co 1.0 ng/L, Cr 2.8 ng/L, Cs 9.8 ng/L, Cu 27 ng/L, Fe 1.1 ng/L, Mn 1.8 ng/L, Ni 17 ng/L, Pb 13 ng/L, Se 0.07 ng/L, Sr 5.7 ng/L, Tl 0.2 ng/L, U 0.1 ng/L, V 0.7 ng/L and Zn 1.2 ng/L. A developed method was applied for trace element biomonitoring of occupationally exposed workers of a beryllium processing enterprise. For preliminary risk assessment technological surface dust had been analyzed by inductively coupled plasma optical emission spectrometry. Based upon results of 50 blood and 40 urine samples analyses occupational exposure evaluation was performed. Exposure risks were found not to exceed acceptable ranges. Possible health hazards were found for Be and also Al, Cr, Mn. Occupational health and safety recommendations for the biomonitored enterprise medical care unit were issued as a result of the current investigation.

Long-term efficacy of a program to prevent beryllium disease.

BACKGROUND: In 2000, a manufacturer of beryllium materials and products introduced a comprehensive program to prevent beryllium sensitization and chronic beryllium disease (CBD). We assessed the program's efficacy in preventing sensitization 9 years after implementation. METHODS: Current and former workers hired since program implementation completed questionnaires and provided blood samples for the beryllium lymphocyte proliferation test (BeLPT). Using these data, as well as company medical surveillance data, we estimated beryllium sensitization prevalence. RESULTS: Cross-sectional prevalence of sensitization was 0.7% (2/298). Combining survey results with surveillance results, a total of seven were identified as sensitized (2.3%). Early Program workers were more likely to be sensitized than Late Program workers; one of the latter was newly identified. All sensitization was identified while participants were employed. One worker was diagnosed with CBD during employment. CONCLUSIONS: The combination of increased respiratory and dermal protection, enclosure and improved ventilation of high-risk processes, dust migration control, improved housekeeping, and worker and management education showed utility in reducing sensitization in the program's first 9 years. The low rate (0.6%, 1/175) among Late Program workers suggests that continuing refinements have provided additional protection against sensitization compared to the program's early years.

Application of Zeeman graphite furnace atomic absorption spectrometry with high-frequency modulation polarization for the direct determination of aluminum, beryllium, cadmium, chromium, mercury, manganese, nickel, lead, and thallium in human blood.

Determination of aluminum (Al), beryllium (Be), cadmium (Cd), chromium (Cr), mercury (Hg), manganese (Mn), nickel (Ni), lead (Pb), and thallium (Tl) concentrations in human blood using high-frequency modulation polarization Zeeman graphite furnace atomic absorption spectrometry (GFAAS) was performed. No sample digestion was used in the current study. Blood samples were diluted with deionized water or 0.1 % (m/v) Triton X-100 solution for Tl. Dilution factors ranged from 1/5 per volume for Be and Tl to 1/20 per volume for Cd and Pb. For Tl, Cd, and Hg, noble metals (gold, platinum, rhodium, etc.) were applied as surface modifiers. To mitigate chloride interference, 2 % (m/v) solution of NH(4)NO(3) was used as matrix modifier for Tl and Ni assessment. The use of Pd(NO(3))(2) as oxidative modifier was necessary for blood Hg and Tl measurement. Validation of the methods was performed by analyzing two-level reference material Seronorm. The precision of the designed methods as relative SD was between 4 and 12 % (middle of a dynamic range) depending on the element. For additional validation, spiked blood samples were analyzed. Limits of detection (LoDs, 3σ, n = 10) for undiluted blood samples were 2.0 µg L(-1) for Al, 0.08 µg L(-1) for Be, 0.10 µg L(-1) for Cd, 2.2 µg L(-1) for Cr, 7 µg L(-1) for Hg, 0.4 µg L(-1) for Mn, 2.3 µg L(-1) for Ni, 3.4 µg L(-1) for Pb, and 0.5 µg L(-1) for Tl. The LoDs achieved allowed determination of Al, Cd, Cr, Mn, Ni, and Pb at both toxic and background levels. Be, Hg, and Tl could be reliably measured at toxic levels only. The methods developed are used for clinical diagnostics and biological monitoring of work-related exposure.

An investigation of aircraft worker anemia: medical surveillance interpretation in an aging workforce.

OBJECTIVE: To identify exposures possibly contributing to anemia cases among hexavalent chromium medical surveillance program enrollees. METHODS: An investigation encompassed metals surveillance programs, extensive workplace sampling and remediation, consultation, evaluation of laboratory accuracy, and follow-up of anemic individuals. RESULTS: Workers had underlying medical conditions that affected surveillance results. There was a systemic error in classification based on hematocrit value. The prevalence of anemia in a workforce averaging 52 years old was 16%. CONCLUSIONS: Anemia may be more prevalent in middle-aged workers than expected. Modern laboratories generally report a calculated hematocrit value, and using hemoglobin for most classification purposes is preferred. Characteristics of a specific workforce, including age, health, hobbies, and diet, should be taken into account when interpreting medical surveillance program findings. The value of a team approach in addressing occupational health problems was demonstrated.

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.

Trace elements in obese Turkish children.

The quality of the diet of obese children is poor. Eating habits may alter micronutrient status in obese patients. In this study, we determined the serum levels of selenium, zinc, vanadium, molybdenum, iron, copper, beryllium, boron, chromium, manganese, cobalt, silver, barium, aluminum, nickel, cadmium, mercury, and lead in obese Turkish children. Thirty-four obese and 33 healthy control subjects were enrolled in the study. Serum vanadium and cobalt levels of obese children were significantly lower than those of the control group (0.244 ± 0.0179 vs. 0.261 ± 0.012 µg/l, p < 0.001, and 0.14 ± 0.13 vs. 0.24 ± 0.15 µg/l, p = 0.011, respectively). There was no significant difference between groups regarding the other serum trace element levels. In conclusion, there may be alterations in the serum levels of trace elements in obese children and these alterations may have a role in the pathogenesis of obesity.

Development and validation of analytical methods for ultra-trace beryllium in biological matrices.

Beryllium (Be) is still not well understood from a toxicological point of view, and studies that involve the determination of different Be compounds species in tissues need to be conducted. In this paper we describe the development and validation of reliable methods for the detection of ultra-trace levels of Be in various biological matrices. Blood and tissues (liver, lung, spleen, and kidney) were used in this study. The samples were digested with a mixture of nitric and perchloric acids for Be and BeAl and an addition of sulfuric acid was made for BeO. The solutions were analyzed by inductively coupled plasma mass spectrometry with (6)Li as internal standard. The detection limits are in the order of 0.02 ng/g for tissue and 0.03 ng/mL for blood, and were compared to existing reference methods. To our knowledge, this is the first study that assesses dissolution of the different Be compounds in biological matrices, while also undergoing a rigorous optimization and complete validation. This method has proven that it is reliable, among the most sensitive available in the literature, and that it can be used in trace toxicological studies for Be.

Beryllium sensitivity among workers at a Norwegian aluminum smelter.

BACKGROUND: Sensitivity to beryllium was investigated among workers at an aluminum smelter in Norway as a consequence of the findings in an occupational exposure survey. METHODS: Three hundred and sixty-two employees and 31 reference persons were tested for sensitization to beryllium with the beryllium lymphocyte proliferation test (BeLPT) based on specifications by the US Department of Energy in 2001. The results are reported as abnormal, borderline, or normal. RESULTS: One person (0.28%) from the aluminum smelter was found to have abnormal results in two separate blood samples and is sensitized to beryllium. Three other persons had one abnormal test that was not confirmed by a second test. One person in the reference group had one abnormal and one normal test result. No borderline samples were detected. None of the employees with one or more abnormal sample results had pot room asthma. The sensitized individual worked in a Soederberg line in 1972-1974. The beryllium concentration in the work atmosphere is estimated to have been similar as today (0.1-0.3 microg/m(3)), but work routines, etc. would cause higher total exposures. CONCLUSIONS: Only one sensitized person of 362 is in line with what is found in other studies in the aluminum industry. The low number, compared with the beryllium handling industry, may be attributable to lower work atmosphere concentrations, beryllium speciation effects, or use of respiratory protection equipment. Pot room asthma does not appear to be associated with beryllium sensitization.

Efficacy of a program to prevent beryllium sensitization among new employees at a copper-beryllium alloy processing facility.

OBJECTIVES: In 2000, 7% of workers at a copper-beryllium facility were beryllium sensitized. Risk was associated with work near a wire annealing/pickling process. The facility then implemented a preventive program including particle migration control, respiratory and dermal protection, and process enclosure. We assessed the program's efficacy in preventing beryllium sensitization. METHODS: In 2000, the facility began testing new hires (program workers) with beryllium lymphocyte proliferation tests (BeLPTs) at hire and at intervals during employment. We compared sensitization incidence rates (IRs) and prevalence rates for workers hired before the program (legacy workers) with rates for program workers, including program worker subgroups. We also examined trends in BeLPTs from a single laboratory. RESULTS: In all, five of 43 legacy workers (IR = 3.8/1,000 person-months) and three of 82 program workers (IR = 1.9/1,000 person-months) were beryllium sensitized, for an incidence rate ratio (IRR) of 2.0 (95% confidence interval [CI] 0.5, 10.1). Two of 37 pre-enclosure program workers (IR = 2.4/1,000 person-months) and one of 45 post-enclosure program workers (IR = 1.4/1,000 person-months) were beryllium sensitized, for IRRs of 1.6 (95% CI 0.3, 11.9) and 2.8 (95% CI 0.4, 66.2), respectively, compared with legacy workers. Test for trend in prevalence rates was significant. Among 2,159 first-draw BeLPTs during 95 months, we identified seven months when high numbers of redraws were required, with one possible misclassification in this facility. CONCLUSIONS: Fewer workers became sensitized after implementation of the preventive program. However, low statistical power due to the facility's small workforce prevents a definitive conclusion about the program's efficacy. These findings have implications for other copper-beryllium facilities, where program components may merit application.

Cumulative sensitization and disease in a beryllium oxide ceramics worker cohort.

OBJECTIVE: We followed a cohort of 136 beryllium oxide ceramics workers from 1992 to 2003, including those who left employment, for beryllium sensitization and chronic beryllium disease (CBD). METHODS: We invited the cohort's participation in current worker surveys in 1992, 1998, 2000, and 2002-2003, and in former worker surveys in 2000-2001 and 2003. We calculated 11-year cumulative incidences (after 1992 initial survey) of sensitization and CBD, both crude and corrected for interval censoring; and period prevalences (including 1992 findings), crude and corrected. RESULTS: In 1992, point prevalences were 6% sensitized and 4% CBD. We obtained follow-up on 83% of 128 not sensitized in 1992. Crude cumulative incidences for sensitization and CBD were 13% and 9%, respectively; corrected were 15% and 11%. Crude period prevalences for sensitization and CBD were 16% and 11%, respectively; corrected were 20% and 14%. Corrected period prevalences for pre-1992 machining work were 30% and 20%. CONCLUSIONS: With repeated testing over 11 years, total sensitization and CBD in this cohort were triple initial 1992 survey results.

Optimizing BeLPT criteria for beryllium sensitization.

BACKGROUND: The beryllium lymphocyte proliferation test (BeLPT) is used to identify persons sensitized to beryllium. ATSDR convened an expert panel of physicians and scientists in April 2006 to discuss this test and to consider what BeLPT test results actually establish beryllium sensitization. The three criteria proposed by panel members were (1)one abnormal result, (2)one abnormal and one borderline result, and (3)two abnormal results. METHODS: Complete algorithms were developed for each of the three proposed criteria. Using single-test outcome probabilities developed by Stange et al. [2004. Am J Ind Med 46:453-462], we calculated and compared the sensitivity, specificity, and positive predictive values (PPVs) for each set of criteria. RESULTS: The overall sensitivity and specificity of the three criteria were similar. When the criteria required confirmation of an abnormal result the PPV was higher--whether the requirement was satisfied by a borderline result, or only by another abnormal result. Confirmation also reduced the likelihood of false positives. The differences between the three criteria decreased as the prevalence of sensitization increased. CONCLUSIONS: A single unconfirmed abnormal is usually insufficient to establish sensitization for an apparently healthy person. When the prevalence of beryllium sensitization in a group is high, however, even a single abnormal BeLPT can be a strong predictor.