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Mortality experience of amosite asbestos factory workers: dose-response relationships 5 to 40 years after onset of short-term work exposure.

A cohort of 820 men in a Paterson, New Jersey, amosite asbestos factory which began work during 1941-1945 was observed from 5 to 40 years after start of work. Most of the cohort had limited duration of work experience (days, weeks, months), though some men worked for several years until the factory closed in 1954. With white males of New Jersey as the control population, Standardized Mortality Ratios (SMRs) of 500 are evident for the cohort for lung cancer and for noninfectious pulmonary diseases (including asbestosis), while being almost 300 for total cancer and about 170 for all causes of death. A statistically significant SMR of almost 200 is seen for colon-rectum cancer. Mesothelioma incidence initially shows a strong relationship with advancing time since onset of exposure and then tails off. The main concern of the study is with dose-response patterns. Response is measured by the mortality for relevant causes of death, while the direct asbestos dosage was measured in two ways. One way was the length of time worked in the factory and the other was the individual's accumulated fiber exposure, calculated by multiplying the aforementioned length of time worked by the estimated fiber exposures associated with the particular job that the worker had in the factory. Whichever measure of dosage is used, it was found that, in general, the lower the dose, the longer it took for adverse mortality to become evident and, also, the smaller the magnitude of that adverse mortality.

Adult↗

Use of hospital discharge data in the surveillance of occupational disease.

Computerized hospital discharge diagnoses are useful for occupational disease surveillance. One thousand one hundred twenty-six individuals with asbestosis and 268 individuals with silicosis were identified in New Jersey for the four-year period 1979-1982. Computer-generated maps help to dramatize the localization of these conditions to certain geographic areas. The attributes and limitations of using hospital discharge diagnoses for occupational disease surveillance are discussed: initial follow-up data are presented for individuals with silicosis.

Data Collection↗

Asbestos disease in sheet metal workers: proportional mortality update.

This paper, updating the findings of an earlier study, provides additional evidence that sheet metal workers in the construction trades are at increased risk for asbestos-related disease. A proportional analysis of cause of death among 331 New York sheet metal workers found a significantly elevated PMR for lung cancer (PMR = 186). In addition, there were six deaths attributable to mesothelioma (three classified as lung cancer deaths) and three death certificates mentioned asbestosis or pulmonary fibrosis, although none of these three deaths were attributed to these diseases.

Actuarial Analysis↗

Using multiple cause of death coding in occupational mortality studies.

Conventional occupational mortality analysis, using underlying cause of death coding, underestimates the contribution of those chronic diseases which are mentioned on the death certificate but which usually do not appear as underlying cause of death. Proportionate occupational mortality analysis, using all the mentioned causes on the Washington State male death records 1968-1984, identified an excess of rheumatoid arthritis in farmers, and asbestosis in plumbers, pipefitters, and steamfitters.

Cause of Death↗

Fissural thickening and exposure to asbestos: occurrence, determinants, and functional impact.

The occurrence and determinants of thickened interlobar fissures were assessed in 147 insulators, in order to test the hypothesis that radiographic abnormalities in minor (FMN) and/or major (FMJ) interlobar fissures are associated with restrictive respiratory impairment, which may reflect early parenchymal lung fibrosis. According to the diagnostic criteria developed, definite interlobar thickening was found in 33 (FMN) and in 73 (FMJ) men, and was frequently associated with the presence of classical asbestos pleural disease, though not parenchymal abnormality. Multivariate analyses did not demonstrate any association between either FMN or FMJ and lung function. Such an association, however, was found in the case of the usual asbestos-related pleural change. These findings suggest that fissural thickening seen on chest radiography represents a component of asbestos pleural disease and not asbestosis.

Adolescent↗

T-cell alveolitis in lung lavage of asbestos-exposed subjects.

In sarcoidosis and idiopathic pulmonary fibrosis, it has been reported that lymphocyte proportions in lung lavage predict the subsequent clinical course. Recent evidence has suggested that lymphocytes are important in the alveolitis of asbestosis. We hypothesized that a greater relative proportion of T-lymphocytes in lung lavage of asbestos-exposed subjects is associated with immune activation and may predict the subsequent clinical course. We assessed lymphocyte subsets in lung lavage and peripheral blood (PB) of 97 asbestos-exposed subjects and 10 unexposed normal, using flow cytometry analysis of monoclonal antibody-treated cells. T-cell alveolitis was defined as follows: [%lymphocytes in lavage x %CD3 in lavage] greater than 2 SD above that product in normals. Eighteen subjects had T-cell alveolitis (group 1) and 79 did not (group 2). There were no significant differences between the groups in age, smoking status, duration of exposure, lung function results, or frequency of plaques or profusion greater than or equal to 1/0. Percent CD2 was higher in lavage of group 1 compared with group 2. There was a trend for higher %Ia in lavage of group 1 compared with group 2. These results identify a subgroup of asbestos-exposed subjects with T-cell alveolitis but no present excess of asbestos-related disease who may be at risk for future asbestos-related disease.

Adult↗

Asbestos fiber analysis in 27 malignant mesothelioma cases.

The asbestos body counts per 5 gm wet lung tissue in 27 (23 pleural and 4 peritoneal) malignant mesothelioma cases derived from 19 autopsy and 8 surgical cases were, according to our own criteria, low level exposure in 13 cases (48.2%), moderate level exposure in 2 cases (7.4%), and high level exposure in 12 cases (44.4%). In our previous study on 235 consecutive autopsy cases, the low level exposure was considered to be environmental, the moderate level was secondary or blue collar, and the high level was occupational. In the present study, about half of the cases examined (44.4%, high level exposure) are closely related to some occupational asbestos exposure and the other half (48.2%) to environmental exposure. The type and size of asbestos fibers from the 12 cases of high level exposure were analyzed and the characteristics were compared with those of cases of low level exposure without lung cancer or mesothelioma. Most fibers analyzed (98%) were longer than 5 microns and thicker than 0.10 micron by our counting rules. In the control group, predominant fibers were tremolite or actinolite. In all the 11 pleural mesothelioma cases, the content of amosite fibers was significantly higher than in the controls. In one case of peritoneal mesothelioma, incipient asbestosis was found and the predominant fibers were crocidolite. It is suggested that the presence of amosite and crocidolite is linked to mesothelioma. The mean lengths of amosite and crocidolite, as detected by our resolution capabilities, were 36.0 and 20.9 microns, and the mean diameters were 0.51 and 0.27 micron, respectively. Both amosite and crocidolite fibers had high aspect ratios (94.2 and 115.4).

Adult↗

Malignant mesothelioma induced in baboons by inhalation of amosite asbestos.

Ten out of 12 South African baboons (Papio ursinus) survived exposure to amosite asbestos dust for periods ranging from 242 days to 898 days at an aerosol level ranging between 1,100 and 1,200 fibers per milliliter. After exposure, they were kept under observation until they died; the total residence time of amosite varied from 1.2-10.2 years. All underwent detailed postmortem necropsy examinations. All baboons had asbestosis. Five of the baboons developed malignant diffuse mesothelioma; three peritoneal, and two pleural with peritoneal invasion. These results indicate that amosite is highly carcinogenic. Since it is difficult to accomplish follow-up of persons exposed to amosite asbestos because of the geographic location of the amosite mines and mills in South Africa (a majority of the workers being migrant laborers from countries bordering on the Transvaal), it is therefore probable that cases of peritoneal mesothelioma have been missed. If human beings are likely to react to amosite as do baboons, epidemiological follow-up should include identification of abdominal as well as thoracic neoplasms.

Animals↗

Intracellular protein binding to asbestos induces aneuploidy in human lung fibroblasts.

Exposure to the natural mineral fiber asbestos causes severe lung-damaging fibrosis and cancer, yet it continues to be used as an industrial insulating material throughout the world. When cultured human lung cells are exposed to asbestos, individual fibers are engulfed into the cytoplasm where they induce significant mitotic aberrations leading to chromosomal instability and aneuploidy. The mechanisms of how asbestosis ultimately leads to lung cancer remain unclear. However, our experiments indicate that intracellular asbestos fibers induce aneuploidy and chromosome instability by binding to a subset of proteins that include regulators of the cell cycle, cytoskeleton, and mitotic process. Moreover, precoating of fibers with protein complexes efficiently blocked asbestos-induced aneuploidy in human lung cells without affecting their uptake by cells. These results provide new evidence that asbestos fibers can contribute to significant spindle damage and chromosomal instability by binding to proteins needed for the assembly and regulation of the cytoskeleton or the cell cycle.

Aneuploidy↗

Morphology of bronchogenic carcinoma in workers formerly exposed to crocidolite at Wittenoom Gorge in Western Australia.

Cytology and histology material from 46 bronchogenic carcinomas occurring in ex-workers from the Wittenoom crocidolite mine and mill in Western Australia and a matched random sample of 234 other bronchogenic carcinomas occurring in Western Australia over the same period were reviewed by a single histopathologist without knowledge of asbestos exposure status. Squamous-cell carcinomas formed 45.7% of the cancers in the asbestos-exposed group but only 32.5% of the cancers in the comparison group. This difference could not be explained by differences in smoking history between the two groups of lung cancer patients or in the type of histopathological material available for review. The excess of squamous-cell cancers was observed in subjects both with and without parenchymal asbestosis.

Adult↗

Inhibition of alveolar macrophage cytotoxicity by asbestos: possible role of prostaglandins.

Asbestosis and silicosis are chronic, fibrosing lung diseases due to prolonged inhalation of asbestos fibers or silica particles. However, little is known about the implication of these toxic dusts on cell-mediated cytotoxicity. Among the first types of cells that are in contact with the dusts are the alveolar macrophages (AM). We studied the effect of different concentrations of UICC chrysotile asbestos and silica on 18-h cytotoxicity of AM against tumor necrosis factor (TNF)-resistant P815 target cells or TNF-sensitive L929 target cells. Rat AM, obtained by bronchoalveolar lavage, were incubated for 2 h with 20, 50, or 100 micrograms/ml chrysotile or silica before the addition of target cells. AM cytotoxicity was significantly inhibited at greater than 20 micrograms/ml of chrysotile. In contrast, silica did not inhibit AM-mediated cytotoxicity at any concentration used. Asbestos, but not silica, caused significant production of PGE2 by macrophages and target cells. Addition of the cyclooxygenase inhibitor indomethacin to our system abolished all inhibition by asbestos. These results suggest that the inhibition of AM-mediated cytotoxicity by chrysotile was caused by prostaglandins, and that fibrogenic particles differ in their capacity to modulate AM function.

Animals↗

Response of mouse lung to crocidolite asbestos. 2. Pulmonary fibrosis after long fibres.

To determine the cellular and fibrogenic responses of the lung to long asbestos fibres, mice were instilled intratracheally with 0.1 mg of a sample of long crocidolite fibres. Animals were killed at intervals to 20 weeks with 3H thymidine injected one h before death. Following bronchoalveolar lavage, an increase in polymorph neutrophils (PMN) and alveolar macrophages (AM) was found during the first week, accompanied by elevated glucosaminidase and alveolar protein levels. Although the PMN number dropped, some were always recovered by lavage to 20 weeks. Early multifocal necrosis of bronchiolar epithelium was followed by a large increase in labelling of epithelial cells and underlying fibroblasts. Epithelial overgrowth of luminal long fibres and inflammatory exudates was followed by giant cell and granuloma formation in the interstitium. After four weeks collagen levels were significantly increased and fibrosis was seen in these peribronchiolar locations. A few small fibres were observed in AM but no evidence of fibrosis was seen in alveolar walls. These findings suggest that injury to bronchial and bronchiolar epithelium allows long fibres to reach the interstitium where subsequent macrophage-fibroblast interactions result in a severe fibrotic reaction that resembles the bronchiolar component of human asbestosis.

Animals↗

Role of transcription factor NF-kappaB in asbestos-induced TNFalpha response from macrophages.

Asbestos exposure in humans is associated with inflammatory, fibrotic, and malignant diseases in the lung. Increasing evidence supports the hypothesis that the production of proinflammatory cytokines such as tumor necrosis factor-alpha (TNFalpha) is an important mediator of the pathologic responses of asbestosis. In this study, we examine the role of nuclear transcription factor-kappaB (NF-kappaB) and free oxygen radicals in asbestos-induced TNFalpha gene and protein expression in lung macrophages. Exposure of the cells to crocidolite asbestos caused a parallel increase in TNFalpha production and NF-kappaB activation, as analyzed by enzyme-linked immunosorbent assay and electrophoretic mobility shift assay. Inhibition of NF-kappaB by SN50, an inhibitor of NF-kappaB nuclear translocation, or by sequence-specific oligonucleotides directed against the NF-kappaB binding site of TNFalpha promoter attenuated the asbestos effect on TNFalpha production. Gene transfection assays using an expression plasmid containing a luciferase reporter gene and a TNFalpha-derived NF-kappaB gene promoter further indicated the dependence of NF-kappaB activation on asbestos-induced gene expression. The effects of asbestos on NF-kappaB and TNFalpha activation were inhibited by oxygen radical scavengers and were enhanced by antioxidant enzyme inhibitors. These results indicate that asbestos-induced TNFalpha gene expression is mediated through a process that involves NF-kappaB activation and free radical reactions.

Animals↗

Lung disease at high altitude.

The lungs are a delicate interface between the atmosphere and our bodies across which oxygen diffuses from the air we breathe to the blood which carries oxygen to the cells and mitochondria. In healthy lungs at sea level where there is a surfeit of oxygen, this process occurs easily, whereas, in lungs with disease it becomes a task which may not be fully successful and hypoxemia may ensue or worsen. At high altitude where the barometric pressure (Pb) and thus the supply of oxygen is lower, the job of getting oxygen to the blood, even in the healthy lung is more difficult, and in the diseased lung it may be impossible. This presentation will review the lungs' responses to high altitude, with emphasis on the abnormal. Both acute and chronic responses of patients with pre-existing lung disease will be reviewed. Pulmonary diseases encountered at high altitude in previously healthy people, such as high altitude pulmonary edema and chronic mountain sickness will be touched on only as they pertain to other patients. Pre-existing lung disease (with and without hypoxemia at sea level) such as obstructive lung diseases (asthma, COPD, emphysema), and restrictive lung diseases (sarcoid, asbestosis, interstitial pulmonary fibrosis) will be discussed in terms of gas exchange, lung mechanics, and treatment at high altitude. Disorders of ventilatory control; e.g., obesity-hypoventilation syndrome and sleep apnea, may present formidable problems, and guidelines for their treatment will be discussed. Infectious lung diseases; e.g., pneumonia, cystic fibrosis, and pulmonary vascular disorders such as chronic mountain sickness, primary pulmonary hypertension, and congenital absence of the pulmonary artery are important disorders that require special attention because of the accentuated hypoxic pulmonary vascular response encountered at high altitude. The purpose therefore, is to provide the medical practitioner with the insight into prevention, recognition, and treatment of pulmonary problems encountered specifically at high altitude, as well as guidance on how best to advise patients with lung disease who want to fly in airplanes and/or ascend to high altitude for work or pleasure.

Altitude↗

Assessing asbestos exposure potential in nonindustrial settings.

The presence of asbestos containing materials (ACM) in office and commercial buildings is a significant environmental problem. Asbestosis, mesothelioma and lung cancer have been linked with industrial exposure to airborne asbestos. The extensive use of asbestos products in buildings has raised concerns about the widespread exposure of the general public to asbestos in nonoccupational settings. The presence of asbestos in a building does not necessarily mean that significant exposure of the occupants of the building has occurred, but it is important that the asbestos be monitored regularly to ensure that fibers do not become airborne. If ACM are contained within a matrix and not disturbed, exposure is unlikely. However, if the asbestos becomes friable (crumbling) or if building maintenance, repair, renovation or other activities disturb ACM, airborne asbestos fibers may be a source of exposure to the occupants of the building. Currently, asbestos exposure assessment is conducted by a phase contrast light microscope (PCM) technique. Due to its inherent limitation in resolution and the generic counting rules used, analysis by the PCM method underestimates the airborne asbestos fiber concentration as compared to analysis by transmission electron microscopy (TEM). It is important that the air monitoring results analyzed by PCM be interpreted carefully in conjunction with a survey by a professional to judge the physical condition of the ACM in buildings. Exposure levels to airborne asbestos fibers vary from day to day and depend on the physical condition of the material involved and the type of operating and maintenance program in place.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollution↗

[Air pollution in an industrial environment and occupational diseases].

Most of the occupational diseases are related to air pollution at the work place. The distribution of gases and vapours and their human absorption are briefly described. The deposition of particles is a function of their physical properties, of the pattern of the respiratory airways and of pulmonary ventilation parameters. Several defence mechanisms also play a role. Illustrative examples are given of occupational diseases caused by solvents, carbon monoxide, metals, dusts (silicosis, asbestosis, pneumoconiosis due to dust of hard metals), allergens and carcinogens. The importance of prevention is emphasized.

Carbon Monoxide↗

[Mesothelioma following occupational contact with asbestos].

From 1975 onwards, mesothelioma is by far the most often seen occupational tumour in Switzerland (about 70%). Between 1969 and 1982, there have been 49 cases registered by the SUVA (Schweizerische Unfallversicherungsanstalt, i.e. Swiss National Accident Insurance Fund). 10 together with asbestosis. Of the first 30 cases, the primary tumour only once was in the peritoneum, in all other cases the tumour always could be located in the pleura. The causative asbestos exposure was found in the production of asbestos cement (9), in the construction and reparation of waggons (6), in the insulation work at chemical plants (5) and in several other industrial work conditions (10). The average exposure time was 21 years. The average interval from exposure to diagnosis 35 years. The survival time after diagnosis about 1 year. Technical prevention consists in substitution of asbestos or elimination of respirable dust (or at least reduction below the TLV). Medical prevention: periodic fitness tests and follow up examinations. New cases should be communicated to the mesothelioma-register in Zurich and to the SUVA, for clarification of the industrial origin.

Asbestos↗

Changes in low molecular weight DNA fragmentation in white blood cells of workers highly exposed to asbestos.

OBJECTIVE: The aim of this study was to determine low molecular weight (LMW)-DNA fragmentation changes after white blood cell (WBC) incubation in lysis buffer followed by constant-field gel electrophoresis (CFGE). WBCs were isolated from blood samples of workers highly exposed to asbestos fibres at the workplace in Germany, and were compared with those from healthy adults. This study was conducted parallel to the study presented in our preceding paper (Marczynski et al. 2000b) in which we described significant increases in the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) adducts in the DNA of white blood cells from the same highly exposed workers relative to the levels found in the control group in all three study years (1994 to 1997). METHOD: We found that 15-h incubation in lysis buffer of WBCs embedded in agarose-plugs from healthy control donors with 2% SDS, proteinase K and Na2-EDTA at 42 degrees C followed by 0.5 h at 4 degrees C produced a characteristic DNA fragmentation pattern below 23 kbp using CFGE. RESULTS: In the 1st year of the study (1994-1995) changes were found in LMW-DNA fragmentation in 54.8% of the asbestos workers studied, compared with the DNA fragmentation pattern of controls. Interestingly, in the 2nd year of the study (1995 1996) changes in DNA fragmentation were found in only 39.9% of exposed subjects. In the 3rd year of the study (1996-1997) the highest number of workers exposed to asbestos (67.3%) with changes in the LMW-DNA fragmentation pattern was found. The Chi-square test for each year of the study revealed significant changes (P < 0.001). These changes may be due to the presence of hydrogen peroxide (H2O2), as has been shown in vitro. It is likely that a Fenton reaction involving the heterolytic reduction of H2O2 by traces of reduced transition metals such as Fe2+ and Cu+ is involved in the fragmentation of DNA. No difference was found in the changes in DNA fragmentation between asbestos-exposed subjects with and without benign asbestos-associated diseases (asbestosis, asbestos-associated pleural plaques). Significant correlations were not found after analysis of the changes in DNA fragmentation in relation to different possible occupational and non-occupational confounding factors, such as the duration of asbestos exposure, the latency period, estimated cumulative fibrous dust dose ("fibre-years"), and non-occupational confounding factors, such as age, smoking status, acute febrile infections, the intake of medicines, aspirin, Ca2+, Mg2+ and/or hormones, the intake of vitamins, and cases of cancer. CONCLUSIONS: Our data confirm that oxidative stress occurs in the WBCs of workers highly exposed to asbestos fibres, thus supporting the hypothesis that asbestos fibres damage cells through an oxidative mechanism. Oxidative stress and oxidative DNA damage may be induced by long-term exposure to asbestos. The new insights into the oxidative effects of asbestos fibres are of great importance because they provide a way forward for new preventive strategies. Preventive and therapeutic approaches using antioxidants should be taken into consideration.

8-Hydroxy-2'-Deoxyguanosine↗