Mesotheliomas - Asbestos Research

BACKGROUND: Scattered patches of crocidolite, one form of asbestos, were found in the surface soil in the rural county of Da-yao in southwestern China. In 1983, researchers from the West China University of Medical Sciences (WCUMS) discovered that residents of two villages in Da-yao had hyperendemic pleural plaques and excessive numbers of pleural mesotheliomas. AIMS: To review and summarise epidemiological studies, along with other relevant data, and to discuss the potential contribution to environmental risk assessment. METHODS: This report is based on a review of several clinical/epidemiological studies conducted by WCUMS researchers since 1984, which included one cross sectional medical examination survey, one clinical/pathological analysis of 46 cases of mesothelioma, and three retrospective cohort mortality studies. Additional information acquired from reviewing original data first hand during a personal visit along with an interview of medical specialists from Da-yao County Hospital was also incorporated.

RESULTS: The prevalence of pleural plaque was 20% among peasants in Da-yao over 40 years of age in the cross sectional survey. The average number of mesothelioma cases was 6.6 per year in the 1984-95 period and 22 per year in the 1996-99 period, in a population of 68 000. For those mesothelioma cases that were histology confirmed, there were 3.8 cases/year in the first period and 9 cases/year in the second. Of the 2175 peasants in this survey, 16 had asbestosis. Lung cancer deaths were significantly increased in all three cohort studies. The annual mortality rate for mesothelioma was 85 per million, 178 per million, and 365 per million for the three cohort studies, respectively. The higher exposed peasants had a fivefold increased mesothelioma mortality compared to their lower exposed counterparts. There were no cases of mesothelioma in the comparison groups where no crocidolite was known to exist in the environment. In the third cohort study, almost one of five cancer deaths (22%) was from mesothelioma. The ratio of lung cancer to mesothelioma deaths was low for all three studies (1.3, 3.0, and 1.2, respectively).

CONCLUSIONS: The observation of numerous mesothelioma cases at Da-yao was a unique finding, due mainly to their lifetime exposure to crocidolite asbestos. The finding of cases dying at a younger age and the relatively high ratio of mesothelioma cases to lung cancer could also be another unique result of lifetime environmental exposure to crocidolite asbestos. Although the commercial use of crocidolite has been officially banned since 1984, the incidence of mesothelioma has continued to show a steady increase, particularly among peasants. Since the latency of mesothelioma is approximately 30-40 years, the ban had little effect in the 1990s. The increased awareness and changes in diagnosis over time may also contribute to the increase. Furthermore, exposure to asbestos stoves and walls continued. The government implemented reduction of these exposures. However, from a public health standpoint, the most important issue is the complete avoidance of further exposure to asbestos."

STUDY OBJECTIVES: To determine patterns in asbestos-induced lung diseases found in older, less exposed workers. DESIGN: Review of a database evaluating lung function, smoking status, form of asbestos-induced lung disease, and radiograph abnormalities. SETTING: Outpatient clinic. PARTICIPANTS: A total of 3383 asbestos-exposed workers referred for independent medical evaluation, including control subjects who lacked asbestos-specific radiograph abnormalities (n = 243), subjects with low International Labor Organization (ILO) scores (n = 2,685), high ILO scores (n = 312), bronchogenic cancer (n = 63), and mesothelioma (n = 80). Of these, 3,327 workers have specific smoking status information and 3,312 workers have lung volume measures.

INTERVENTIONS: Chest radiographs were interpreted by a certified B-reader, and abnormalities were quantified according to the ILO scoring system. Spirometry and lung volume measurement were performed. Subjects completed a self-administered questionnaire that was reviewed at the time of examination. Control subjects were screened on two separate occasions at least 10 years apart to exclude subclinical or slowly progressive asbestos-induced lung disease.

MEASUREMENTS AND RESULTS: The mean age of the population was 65.1 +/- 9.9 years, and the latency was 41.4 +/- 10.1 years (+/- SD). Most subjects (41.8%) had normal pulmonary function. Obstruction was the most common pulmonary function abnormality (25.4%), followed by restriction (19.3%) and a mixed pattern (6.0%). Most subjects (79.4%) had low ILO scores. Benign pleural abnormalities were the only findings in 54% of subjects with low ILO score. Subjects with high ILO scores were older, smoked more, and had a longer latency than subjects with low ILO scores and control subjects. Smokers were younger, had a shorter latency, and had paradoxically greater ILO scores than nonsmokers. Subjects with bronchogenic cancer and mesothelioma had longer latencies than control subjects and subjects with benign asbestos-induced lung disease. CONCLUSIONS: Asbestos-induced lung disease today is characterized by low ILO scores, long latencies, greater disease magnitude in smokers, and a normal or obstructive pattern of pulmonary function abnormality. Spirometric evaluation in the absence of lung volume measurements caused misclassification that resulted in overestimation of the presence of a restrictive pattern of pulmonary function."

"Asbestos has been recognised as a potential health hazard since the 1940s. Of the two major species of asbestos; white asbestos (chrysotile) and blue asbestos (crocidolite), both of which are hazardous. The workers at extraction facilities are at the greatest risk of exposure to asbestos and, therefore, the development of asbestos-related diseases, commonly mesothelioma. However, other individuals at a high risk of exposure include asbestos-cement workers, insulation workers and ship-yard workers.

Environmental exposure to asbestos can occur as a result of living in areas either characterised by natural outcrops of asbestos or asbestos-related materials, or those close to asbestos-producing or -using plants. Unfortunately, man-made fibre alternatives to asbestos, such as rock and slag-wool and glass wool, have also been shown to have a detrimental effect on human health.

A characteristic of mesothelioma is that there is a long latency period (20-30 years) before the signs and symptoms of the disease become apparent. In addition, diagnosis of the disease can be difficult. The use of biological markers, such as tissue polypeptide antigen, may play a useful role in the early detection of the disease in individuals at risk."

"A survey of 610 pleural mesotheliomas disclosed 40 familial cases. The diagnosis was histologically based in 39 cases, and confirmed by necropsy in 30. Occupational data were collected from the patients or from their relatives by personal interviews. Routine lung sections were examined for asbestos bodies in 32 cases. In 15 cases asbestos bodies were isolated after chemical digestion of lung tissue.

Familial mesotheliomas included 31 men and 9 women (age range 44-93 yr, mean 70.7, median 71.0). In 15 families there were blood relations between (or among) the members involved. All the patients had been exposed to asbestos, mostly in the shipyards. Asbestos bodies were found on routine lung sections in 27 cases. Asbestos bodies after isolation ranged from 70 bodies to about 900,000/g dried lung tissue. Latency periods (time intervals between first exposure to asbestos and diagnosis) ranged between 25 and 70 yr (mean 52.0, median 54.0).

The occurrence of mesothelioma among subjects with blood relations suggests that genetic factors might play a role in determining the susceptibility to asbestos-related cancer. Familial cases among persons without blood relations raise the question if environmental factors that members of a family share, may act as co-factors in asbestos-related mesothelioma."

"Throughout the history of automobile development, chrysotile asbestos has been an essential component of vehicle brake linings and pads. Acceptable alternatives were not fully developed until the 1980s, and these were installed in vehicles produced over the past decade. This article presents a "state-of-the-art" analysis of what was known over time about the potential environmental and occupational health hazards associated with the presence of chrysotile asbestos in brake linings and pads. As part of this analysis, the evolution of automobile brakes and brake friction materials, beginning with the early 1900s, is described.

Initial concerns regarding exposures to asbestos among workers involved in the manufacture of friction products were raised as early as 1930. Between 1930 and 1959, eight studies were conducted for which friction product manufacturing workers were part of the population assessed. These studies provided evidence of asbestosis among highly exposed workers, but provided little information on the magnitude of exposure. The U.S. Public Health Service proposed the first occupational guideline for asbestos exposure in 1938. The causal relationship between asbestos exposure and lung cancer was confirmed in 1955 in asbestos textile workers in the United Kingdom, and later, in 1960, in South Africa, mesothelioma was attributed to asbestos exposure to even relatively low airborne concentrations of crocidolite. Between 1960 and 1974, five epidemiology studies of friction product manufacturing workers were conducted. During this same time period, the initial studies of brake lining wear (dust or debris) emissions were conducted showing that automobile braking was not a substantial contributor of asbestos fibers greater than 5 microm in length to ambient air.

The first exposure surveys, as well as preliminary health effects studies, for brake mechanics were also conducted during this period. In 1971, the Occupational Safety and Health Administration promulgated the first national standards for workplace exposure to asbestos. During the post-1974 time period, most of the information on exposure of brake mechanics to airborne asbestos during brake repair was gathered, primarily from a series of sampling surveys conducted by the National Institute of Occupational Safety and Health in the United States."

"The aim of this study was to review and reappraise the clinical and CT features of malignant peritoneal mesothelioma (MPM), and to discuss differential diagnosis. The history, clinical, and laboratory data, and imaging studies of 11 patients with a histologically proven diagnosis of MPM, were retrospectively reviewed.

Our patients consisted of 7 women and 4 men, with a median age of 48 years (age range 40-55 years). There was a definite history of significant asbestos exposure in 6 patients. Abdominal swelling (9 of 11) was the most common presenting symptom. The mean serum CA-125 (normal value 1.2-32 U/ml) level was 230 U/ml (range 19-1000 U/ml). The most common radiological findings were extensive or moderate amounts ascites (11 of 11), irregular or nodular peritoneal thickening (11 of 11), omental involvement (10 of 11), mesentery involvement (9 of 11), pleural thickening, plaques or calcification (7 of 11), pleural effusion (6 of 11), and bowel wall thickening (5 of 11). Two patients had large upper abdominal masses. Computed tomography findings of MPM are nonspecific and inadequate to pinpoint specific diagnosis.

The diagnosis requires histological demonstration which is commonly made by an image or laparoscopic-guided biopsy. Pleural changes suggesting asbestosis combined with CT findings and high CA-125 levels can suggest, but are not diagnostic of, mesothelioma. Suggesting the diagnosis of MPM is important because histological and immunohistochemical tests are needed for diagnostic accuracy."

"This paper focuses on three aspects of forecasting models for asbestos-related disease/injuries relating to the Manville asbestos case: (1) The structure of forecasting models for asbestos-related personal injuries.

(2) The epidemiologic evidence supporting the selected model structure and the constraints on the modeling assumptions imposed by that evidence.

(3) The range of uncertainty associated with projections based on these forecasting models and issues relating to decision making under uncertainty."

"Asbestos-related illness usually arises at least 10 to 20 years after initial exposure. In many instances, patients may be unaware of the source of exposure. Although community-based exposures are unusual, recent events indicate that both communities and workers may have had significant exposure to asbestos contained within vermiculite.

Physicians should obtain a medical history as outlined above when examining workers or community members who believe they have been significantly exposed to vermiculite. In addition, pulmonary function testing and chest radiographs should be obtained. If these are normal and there is no ongoing exposure, it is likely that no further evaluation is required. Physicians should have a radiologist familiar with occupational lung diseases read films. Patients may ask that a "B" reader, a physician who is certified by the National Institute for Occupational Safety and Health to read x-rays for changes related to the pneumoconioses, review their films. Facilitating smoking cessation and providing routine immunizations are important secondary preventive measures. Workers exposed to asbestos should receive ongoing screening as specified by the Occupational Safety and Health Administration.

Over the last several decades, numerous epidemiologic studies have evaluated the efficacy of lung cancer screening. Period chest radiographs and sputum cytology have not been shown to increase lung cancer survival rates. Recent studies have demonstrated the potential benefit of scanning in the early detection of lung cancer. Although encouraging, these studies do not yet support the use of imaging for the routine screening of high-risk populations as required by the Occupational Safety and Health Administration."

"The pathogenesis of asbestos-related lung diseases is complicated and still poorly understood. Studies on animal models and cell cultures have indicated that asbestos fibres generate reactive oxygen and nitrogen species and cause oxidation and/or nitrosylation of proteins and deoxyribonucleic acid as a marker of cell injury. These effects are potentiated by the inflammation caused by the fibres.

Recent studies have shown that individual variability in the antioxidant and/or detoxifying mechanisms probably has an important role in the development of asbestos-related lung diseases. Asbestos fibres cause both cell proliferation and apoptosis by multiple mechanisms, one of them being activation of signal transduction pathways by reactive oxygen and nitrogen species. Asbestos activates transcription factors such as nuclear factor kappa B, which has been shown to lead to the upregulation of antioxidant enzymes, most importantly manganese superoxide dismutase. This enzyme is also overexpressed in asbestos-related human malignant mesothelioma, whereas the induction of other antioxidant enzymes (copper-zinc superoxide dismutase, catalase, glutathione peroxidase) by asbestos fibres appears to be marginal.

The significance of antioxidant enzymes in asbestos related diseases has, however, remained unclear. Furthermore, previous studies have not been able to offer successful therapies to the patients with asbestos-associated diseases. Only an improved understanding of the pathogenetic mechanisms in the human lung provides a basis for future therapies for asbestos-related diseases."

Mesotheliomas - Asbestos Research Links

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