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Asbestos exposure and multiple primary tumors.

Recently we observed 5 patients with multiple primary tumors who also had a history of occupational asbestos exposure. Two patients had a lung carcinoma and a colon carcinoma and 3 others had 2 distinct pulmonary carcinomas. Most of the attending physicians were unaware of the patient's occupational risk for asbestos exposure and the resultant health hazards. Therefore, we review the uses of asbestos and occupations at risk for asbestos exposure.

Adenocarcinoma↗

Malignant mesothelioma arising after direct application of asbestos and fiber glass to the pericardium.

A case of mesothelioma, apparently arising in the pericardium, is reported in a patient who, 15 years previously, had been treated for angina pectoris by dusting of the pericardial cavity with a mixture of fibrous dusts. At autopsy, transparent fibers and ferruginous bodies were present within the pericardium. Electron diffraction and microprobe analysis indicated that approximately two thirds of the fibers were tremolite and anthophyllite asbestos, and the remainder, fiber glass. Development of mesothelioma in laboratory animals has been reported after intrapleural deposition of asbestos and other fibers, but in humans, the link between exposure to asbestos and mesothelioma has always been based on epidemiologic data and the retrospective finding of asbestos in tissues. To our knowledge, this is the first example of a malignant mesothelioma in a human associated with direct mesothelial contact with fibrous dusts.

Angina Pectoris↗

Asbestos bodies in bronchoalveolar lavage.

Asbestos bodies (AB) were counted in bronchoalveolar lavage (BAL) fluid from 62 patients with suspected asbestos related diseases, 2 patients with known exposure to asbestos but without related disease, and 40 control subjects. BAL fluid contained AB in all patients with obvious exposure (28 of 28), including the 2 without related disease, in most patients with suspected exposure (26 of 28), as well as in 5 of 8 patients without known exposure but with suspicion of asbestos related disease (mesothelioma or pleural plaques). Among the 40 control subjects, the results in 5 were positive but to a low degree (less than 1 AB/ml of fluid). Quantitative analysis correlated with the type of disease: AB counts were higher in patients with interstitial lung disease than in those with benign (p less than 0.02) or malignant (p less than 0.01) pleural disease. Only 9 of 13 patients with mesothelioma had a positive lavage. In conclusion, the finding of AB in BAL fluid correlates with the occupational risk and can disclose unknown exposure better than a questionnaire, but a positive lavage is not a proof of disease. Quantitative differences in AB counts suggest a different pathogenesis for pleural and parenchymal disease.

Adult↗

A comparison of the ferruginous body and uncoated fiber content in the lungs of former asbestos workers.

Tissue samples from 12 former asbestos workers were digested and analyzed for ferruginous body and uncoated fiber populations. It was noted that there were large numbers of nonasbestos fibers in each of the samples. In some samples, these fibers constituted over 80% of the total uncoated fibers, and they could greatly influence the data as to asbestos content of the tissue unless differentiated by light and electron microscopic techniques, such as X-ray energy-dispersive analysis. There were great variations in the numbers of uncoated fibers per ferruginous body between the individual workers. The digested samples from lungs of 2 workers yielded no ferruginous bodies by light microscopy, even though these samples by electron microscopy contained respective loads of 780,000 and 1.2 million uncoated amphibole fibers per gram. Light microscopy examination of adjacent tissues confirmed mild fibrosis in both workers. Ferruginous bodies serve as a general marker for asbestos exposure. However, our data suggest that their absence in tissue with interstitial fibrosis from a worker with previous occupational exposure may not be sufficiently conclusive to rule out asbestos-induced disease. Rather, as shown by our data, individual exceptions may require correlated analysis by analytical electron microscopy in order to define particulate load and support the diagnosis of the disease.

Asbestos↗

Lung function and exercise performance in smoking and nonsmoking asbestos-exposed workers.

Evaluation of impairment caused by exposure to an occupational toxin can be complicated by additional exposure to other injurious agents. Because cigarette smoking is common and cigarettes are implicated in obstructive lung disease and cardiovascular diseases, we assessed the contribution of smoking to functional abnormalities in a group of asbestos-exposed shipyard workers. Seventy-three workers who never smoked were paired with 73 current smokers by age and asbestos exposure. Pulmonary function and performance during cycle incremental exercise were compared between the 2 groups. Nonsmokers had significantly higher VC, FEV1, FEV1/VC, and diffusing capacity for carbon monoxide than did smokers. Only 3 of the 73 nonsmokers but 23 of the 73 smokers had a FEV1/VC below the 95% confidence limit of predicted value. The FEF25-75%, on the other hand, failed to identify additional subjects with obstruction not found by the FEV1/VC. During exercise, despite no difference in maximal heart rate, the maximal O2 uptake (VO2max) and oxygen-pulse were lower among smokers. In addition, smokers more frequently had abnormal AaPO2 at maximal exercise. Of 33 smokers who had a VO2max less than 80% of predicted, 16 were judged to have cardiac disease, whereas only 2 appeared to be limited by obstruction. Only 15 of the 73 nonsmokers had a VO2max less than 80%. We conclude that cigarette smoking was the major contributing factor to the obstructive lung disease observed in asbestos workers, and it also had a strong influence on the occurrence, nature, and magnitude of exercise limitation. The history of cigarette smoking has an important effect on the assessment of impairment from asbestos.

Aged↗

Novel cell imaging techniques show induction of apoptosis and proliferation in mesothelial cells by asbestos.

We developed in situ dual-fluorescence detection techniques for measuring apoptosis and proliferation simultaneously in single dishes of cells. The deoxyribonucleic acid (DNA)-specific labeling method, terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate nick-end labeling (TUNEL), first was used in conjunction with a 4',6-diamidino-2-phenylindole (DAPI) counterstain to detect and measure morphologic characteristics of apoptotic rat pleural mesothelial (RPM) cells isolated from Fischer 344 rats and exposed to 300 microM hydrogen peroxide (H2O2). For this purpose, 100 TUNEL-positive nuclei were measured while being viewed with DAPI counterstaining for area, perimeter, longest diameter, and average diameter, using imaging software and an image-collection apparatus. We then exposed cells to a range of concentrations of crocidolite asbestos and putative apoptotic and mitogenic agents. Exposure to crocidolite asbestos (5 microg/cm2) caused a striking dose-dependent apoptotic response at 24 h, 48 h, and 72 h. The nonfibrous crocidolite analogue riebeckite failed to induce apoptosis. At 24 h, tumor necrosis factor-alpha (TNF-alpha) (10 ng/ml) caused an increase in apoptotic nuclei. A second method, utilizing an antibody to 5'-bromodeoxyridine (BrdU) and oxazole yellow homodimer (YOYO), showed a dose-dependent increase in proliferation occurring in cells exposed to asbestos (5 microg/cm2) at 48 h and 72 h. In addition, increased numbers of rat pleural mesothelial (RPM) cells exposed to 12-O-tetradecanoylphorbol-13-acetate (TPA), TNF-alpha, and epidermal growth factor (EGF) exhibited incorporation of BrdU at these time points, although total numbers of cells per unit area were unchanged. Results indicate a dynamic balance between apoptosis and increased DNA synthesis after exposure of mesothelial cells to asbestos.

Animals↗

Restrictive lung function and asbestos-induced pleural fibrosis. A quantitative approach.

To assess further the clinical significance of asbestos-induced pleural fibrosis, we used a computer algorithm to reconstruct images three dimensionally from the high-resolution computerized tomography (HRCT) scan of the chest in 60 asbestos-exposed subjects. Pulmonary function tests, chest radiographs, and HRCT scans were performed on all study subjects. The volume of asbestos-induced pleural fibrosis was computed from the three-dimensional reconstruction of the HRCT scan. Among those with pleural fibrosis identified on the HRCT scan (n = 29), the volume of the pleural lesion varied from 0.01% (0.5 ml) and 7.11% (260.4 ml) of the total chest cavity. To investigate the relationship between asbestos-induced pleural fibrosis and restrictive lung function, we compared the computer-derived estimate of pleural fibrosis to the total lung capacity and found that these measures were inversely related (r = -0.40; P = 0.002). After controlling for age, height, pack-years of cigarette smoking, and the presence of interstitial fibrosis on the chest radiograph, the volume of pleural fibrosis identified on the three-dimensional reconstructed image from the HRCT scan was inversely associated with the total lung capacity (P = 0.03) and independently accounted for 9.5% of the variance of this measure of lung volume. These findings further extend the scientific data supporting an independent association between pleural fibrosis and restrictive lung function.

Aged↗

Head and neck surveillance program for factory personnel exposed to asbestos.

Personnel at a local factory that manufactures brake linings and discs in which asbestos is a major component were requested to participate in an on-site surveillance program to detect head and neck abnormalities, specifically cancer. Demographic data included smoking histories and job descriptions that could be delineated into high- and low-asbestos exposure groups. In the first year, 322 factory workers had no cancer identified but 15% had laryngeal abnormalities, mostly laryngitis. Ninety-seven percent of those workers with abnormal findings were smokers, but there were a significant number in the high-asbestos group irrespective of smoking histories. From this report, high-risk individuals were identified and requested to continue in the program for monitoring. In the subsequent 3 years, these individuals and new personnel were examined. Similar results were obtained in that laryngitis was noted in 24% (95% of whom were smokers) with a stronger statistical association with the high-asbestos group. More important, one person previously identified as high-risk was noted to have stage I squamous cell carcinoma and was treated with radiotherapy. The results of this program suggest that individuals at high risk for the development of head and neck cancer can be identified and that such surveillance programs should be implemented in similar arenas.

Adult↗

Lung asbestos bodies and pulmonary cancer in subjects without occupational exposure.

Lung asbestos bodies were searched for in 65 subjects with pulmonary cancer and without occupational exposure and in 65 matched controls. No significant association between the presence of asbestos bodies and occurrence of lung cancer was found. Nevertheless, adenocarcinoma was significantly associated with the presence of lung asbestos bodies in men. The latter result suggest that, even in non-professionally exposed subjects, the possibility of relationships between asbestos exposure and lung cancer cannot be excluded.

Adenocarcinoma↗

Asbestos and peritoneal mesothelioma among college-educated men.

The proportion of peritoneal mesotheliomas among all mesotheliomas has been decreasing, leading some to suggest that peritoneal mesothelioma occurs only after high levels of exposure to asbestos. To investigate the relationship between asbestos exposure and the development of peritoneal mesothelioma, a case-control study examined 40 cases of primary peritoneal mesothelioma from a single institution. This series differed from previous reports in that 75% of the cases and controls had attended college. Results show an odds ratio of 6.6 for asbestos exposure among this group of primary peritoneal mesothelioma cases with relatively slight asbestos exposures.

Asbestos↗

Asbestos in Belgium: use and abuse.

It took 50 years for Belgium to recognize asbestosis; mesothelioma and lung cancer were recognized as occupational diseases caused by asbestos in 1982 and 1999, much later than in neighboring countries. Only salaried workers can claim compensation from the Occupational Diseases Fund. The right to reparation is thus denied to most victims because many have been self-employed: mechanics, electricians, painters, roofers, carpenters, plumbers, etc. Compensation was also denied to people who became ill through exposures to the workclothes of family members or pollution from asbestos factories near their homes. The main obstacles facing asbestos victims are legal and judicial. For instance, an employer is not liable, even for gross negligence. Victims are not allowed to claim if 20 years have passed since their exposures to asbestos. Changes in Belgian legislation are sorely needed.

Asbestos↗

Asbestos-related diseases in Italy: epidemiologic evidences and public health issues.

Epidemiologic information about asbestos-related diseases in Italy, derived from mortality data, epidemiologic surveillance, and analytical studies, is presented. These systems evidence exposures to asbestos and relative risks for populations exposed in work environments and also in the general environment, and provide objective data to identify sources of exposure and for risk management. Limitations and perspectives of Italian studies are considered, and public health issues evaluated: the risk for migrants, social security aspects, and asbestos-related disease in the courts. Although asbestos use was banned in 1992, information and risk communication efforts should be implemented to empower affected individuals and communities and to pursue equitable allocation of resources for primary prevention and health surveillance.

Asbestos↗

Abuse of epidemiology: automobile manufacturers manufacture a defense to asbestos liability.

Much of the "debate" about the relationship between asbestos exposure from automobile brake work and asbestos-induced cancer has been fueled by studies that have been funded by corporations with billions at stake in tort litigation. The authors explore how asbestos-lined brake manufacturers have corrupted medical literature to escape liability, analyzing studies funded by these companies to enable them to claim that work with asbestos brake linings never causes mesothelioma. They reveal how the companies have redefined scientific criteria for the determination of cause-effect relationships and manipulated scientific data to give the impression of an absence of effect. But the absence of evidence is not evidence of the absence of an effect.

Asbestos↗

Banning asbestos in Asia: campaigns and strategies by the Asian Network for the Rights of Occupational Accident Victims (ANROAV).

China, India, Indonesia, and Thailand are among the largest consumers of asbestos. Because markets in the West are dwindling, asbestos is heavily promoted in Asia. In spite of widespread usage, asbestos-related diseases are surprisingly few and reported cases of mesothelioma are rare in Asia except in Japan, Korea, and Singapore. The problem lies in diagnosis. Most of the asbestos-related diseases are not diagnosed in Asia and thus do not appear in government statistics. This deadly substance is killing workers. Unless drastic action is taken to stop its use, Asian workers as well as the general population will pay a heavy price.

Asbestos↗

Chest CT screening of asbestos-exposed workers: lung lesions and incidental findings.

The objective of the present study is to determine the feasibility of chest computed tomography (CT) in screening for lung cancer among asbestos-exposed workers. In total, 633 workers were included in the present study and were examined with chest radiography and high-resolution CT (HRCT). A total of 180 current and ex-smokers (cessation within the previous 10 yrs) were also screened with spiral CT. Noncalcified lung nodules were considered positive findings. The incidental CT findings not related to asbestos exposure were registered and further examined when needed. Noncalcified lung nodules were detected in 86 workers. Five histologically confirmed lung cancers were found. Only one of the five cancers was also detected by plain chest radiography and three were from the group of patients with a pre-estimated lower cancer probability. Two lung cancers were stage Ia and were radically operated. In total, 277 individuals presented 343 incidental findings of which 46 required further examination. Four of these were regarded as clinically important. In conclusion, computed tomography and high-resolution computed tomography proved to be superior to plain radiography in detecting lung cancer in asbestos-exposed workers with many confounding chest findings. The numerous incidental findings are a major concern for future screenings, which should be considered for asbestos-exposed ex-smokers and current smokers.

Aged↗

An assessment of asbestos body formation in extrapulmonary sites: liver and spleen.

STUDY OBJECTIVES: Asbestos bodies (ABs) form as asbestos fibers become coated by a cellular iron- and protein-rich matrix. ABs have been reported in lymph nodes and a few extrapulmonary sites, but no data exist as to their formation outside of the lung. It is not clear whether the AB found in these extrapulmonary areas have been transported as mature structures from the lung or formed at the extrapulmonary site. This study was designed to determine if ABs are produced in extrapulmonary sites. The guinea pig efficiently forms ferruginous bodies in the lung and so it was chosen as a model to test the coating efficiency of amosite asbestos fibers in lung, liver and spleen. DESIGN: Sized amosite asbestos (5 mg) was administered either endotracheally into lung (n = 2) or directly into liver (n = 4) and spleen (n = 4) of healthy 10-week-old male guinea pigs. The lung, liver and splenic tissues were removed at 40 and 180 days post inoculation and were examined histologically for the presence of AB via light microscopy. Uncoated fibers isolated from the tissues were characterized by electron microscopy. The coating efficiency was calculated as a ratio of uncoated/coated fibers per organ. RESULTS: The coating efficiency ratios of fibers that were collected at 40 days post-injection from the individual sites were: lung - 350:1, liver - 4200:1, and spleen - 220,000:1. At 6 months post-injection the ratios for the individual sites consisted of: lung - 176:1, liver - 11,000:1, and spleen - 1000:1. CONCLUSION: This study indicates that AB can be formed in extrapulmonary sites and that the coating efficiency in the lung is much greater than that within the liver or spleen.

Animals↗

Asbestos content of omentum and mesentery in nonoccupationally exposed individuals.

Asbestos fibers in occupationally exposed individuals relocate from the lung to extrapulmonary sites. A mechanism for relocation is via the lymphatic circulation. Indeed, asbestos fibers have been found in lymph nodes as well as pleural plaques. Our laboratory has recently shown that asbestos fibers also reach the mesentery and omentum in the peritoneal area where a small percentage of mesotheliomas occurs in exposed individuals. The present study uses light and analytical transmission electron microscopy for defining the asbestos burden in digested lung, omentum, and mesentery tissues from individuals considered as representing the general population in East Texas. The findings, when compared with previous data from occupationally exposed individuals, indicate extreme contrasts as to the level and types of fiber burden between individuals representing the groups.

Adolescent↗

Asbestos and cancer of the larynx: is there a relationship?

A head and neck examination was conducted on 322 personnel in a plant that manufactures brake linings and disks where asbestos is a major component. The personnel were categorized according to occupational risk, duration of employment, and smoking and alcohol habits. Thirty-nine percent had abnormalities, the most common being laryngitis (15%), deviated nasal septum (13%), and neck mass (5.3%). Six members required a biopsy, but no cancer was discovered. Of 47 personnel with laryngitis, 46 were smokers (P less than .01). In regard to asbestos exposure, 20% of the high-risk group had laryngitis, compared to 11% in the low-risk group (P less than .05). The data were compared to a previously prepared longitudinal study of plant personnel (2057 individuals and 37,361.5 person years), where three cases of laryngeal cancer had been observed (0.77 expected). As these cases involved smokers with limited asbestos exposure, neither the longitudinal or cross-sectional data could support asbestos as an etiologic factor for laryngeal cancer, but it may act as an irritant.

Adult↗