Asbestos lung burden and asbestosis after occupational and environmental exposure in an asbestos cement manufacturing area: a necropsy study

OBJECTIVE: The largest Italian asbestos cement factory had been active in Casale Monferrato until 1986: in previous studies a substantial increase in the incidence of pleural mesothelioma was found among residents without occupational exposure to asbestos. To estimate exposure to asbestos in the population, this study evaluated the presence of histological asbestosis and the lung burden of asbestos fibres (AFs) and asbestos bodies (ABs). METHODS: The study comprises the consecutive series of necropsies performed at the Hospital of Casale Monferrato between 1985 and 1988. A sample of lung parenchima was collected and stored for 48 out of 55 necropsies. The AF concentration was measured with a TEM electron microscope with x ray mineralogical analysis. The ABs were counted and fibrosis evaluated by optical microscopy. The nearest relative of each subject was interviewed on occupational and residential history. Mineralogical and histological analyses and interviews were conducted in 1993-4. RESULTS: Statistical analyses included 41 subjects with AF, AB count, and interview. Subjects without occupational exposure who ever lived in Casale Monferrato had an average concentration of 1500 AB/g dried weight (gdw); Seven of 18 presented with asbestosis or small airway lung disease (SAL). G2 asbestosis was diagnosed in two women with no occupational asbestos exposure. One of them had been teaching at a school close to the factory for 12 years. Ten subjects had experienced occupational asbestos exposure, seven in asbestos cement production: mean concentrations were 1.032 x 10(6) AF/gdw and 96,280 AB/gdw. Eight of the 10 had asbestosis or SAL. CONCLUSION: The high concentration of ABs and the new finding of environmental asbestosis confirm that high asbestos concentration was common in the proximity of the factory. Subjects not occupationally exposed and ever living in Casale Monferrato tended to have higher AB concentration than subjects never living in the town (difference not significant). The concentrations of ABs and AFs were higher than those found in other studies on nonoccupationally exposed subjects.     

Asbestos: current knowledge and perspectives

Diseases due to asbestos inhalation are not only a concern for occupational physicians, but also for general practicioners and pneumologists. The real or supposed risk has extended beyond the factories employing "primary asbestos workers" to thousands of people exposed to this material or simply working in buildings insulated with asbestos. The spectrum of asbestos-related diseases has changed: asbestosis (parenchymal fibrosis due to asbestos) tends to disappear, whereas the incidence of pleural lesions, which can be associated with lower cumulative exposures, increases. Patients with asbestos related diseases do not die any more from respiratory failure but from late neoplastic complications, such as mesothelioma and lung cancer. The lack of interest and of training in occupational medicine leads to an underrecognition and an underestimation of cancers due to asbestos by the physicians. Recent progresses in CT imaging and evaluations of exposure to fibers through mineralogical analysis of lung samples have led to improve the diagnostic approach of fiber-related diseases.     

Pleural malignant mesothelioma with osseous cartilaginous and rhabdomyogenic differentiation

A 63-year-old man, who was formerly an asbestos factory worker who had been followed due to asbestosis, and was admitted to our hospital with left chest pain and dyspnea on exertion. A chest X-ray and chest computed tomogram (CT) on admission revealed a large tumor in the left lung field. Percutaneous needle biopsy determined that the tumor was a sarcoma. No clinical response was obtained by systemic chemotherapy. The autopsy revealed diffuse malignant mesothelioma of sarcomatous type with osseous, cartilaginous and rhabdomyogenic differentiation. Osseous and cartilaginous differentiation in a malignant mesothelioma is rare, and the presence of a malignant rhabdomyogenic component is the first to be described in the Japanese literature.     

Malignant lymphoma involving the penis following malignant pleural mesothelioma

A 74-year-old man who had been diagnosed with malignant mesothelioma developed malignant lymphoma of B-cell origin involving the penis. He had a history of occupational exposure to asbestos as a construction worker. The association of malignant mesothelioma with lymphoma is rare, and the possibility of asbestos exposure as a common etiology is discussed. The intense stimulation of B lymphocytes and decreased T lymphocyte activity in asbestos-exposed populations may result in development of B-cell malignancies. Though the relationship between asbestos exposure and malignant mesothelioma is firmly established, the relationship between asbestos exposure and lymphoma remains to be investigated.     

Future increase of the incidence of mesothelioma due to occupational exposure to asbestos in the past

OBJECTIVE: To estimate the future course of mesothelioma mortality as a result of occupational exposure to asbestos in the past. DESIGN: Cohort age model. SETTING: Department of Public Health, Erasmus University Rotterdam, the Netherlands. METHODS: A cohort age model was developed, based upon age-specific rates of pleural mesothelioma mortality during 1969-1994. This model was linked to the future trend in mortality among Dutch men as projected by the Central Bureau for Statistics in order to predict the future course of mesothelioma mortality in the period 1995-2030. RESULTS: In the next 35 years about 20,000 cases of pleural mesothelioma among men are expected. The projection results in a peak of annual male mesothelioma deaths of approximately 700 in about the year 2018. After 2020 the annual mortality will rapidly decline to about 450 cases in 2030. It is expected that this rapid decline will continue after 2030. In the 1943-1947 birth cohort pleural mesothelioma may account for 0.87% of all deaths. Exposure to asbestos at work largely explains this particular mortality pattern. CONCLUSION: Exposure to asbestos at work has created an important public health problem among Dutch men.     

Mesothelioma in Quebec chrysotile miners and millers: epidemiology and aetiology

In a cohort of some 11,000 men born 1891-1920 and employed in the Quebec chrysotile production industry, including a small asbestos products factory, of 9780 men who survived into 1936, 8009 are known to have died before 1993, 38 probably from mesothelioma--33 in miners and millers and five in factory workers. Among the 5041 miners and millers at Thetford Mines, there had been 4125 deaths from all causes, including 25 (0.61%) from mesothelioma, a rate of 33.7 per 100,000 subject-years; the corresponding figures for the 4031 men at Asbestos were eight out of 3331 (0.24%, or 13.2 per 100,000 subject-years). At the factory in Asbestos, where all 708 employees were potentially exposed to crocidolite and/or amosite, there were 553 deaths, of which five (0.90%) were due to mesothelioma; the rate of 46.2 per 100,000 subject-years was 3.5 times higher than among the local miners and millers. Six of the 33 cases in miners and millers were in men employed from 2 to 5 years and who might have been exposed to asbestos elsewhere; otherwise, the 22 cases at Thetford were in men employed 20 years or more and the five at Asbestos for at least 30 years. The cases at Thetford were more common in miners than in millers, whereas those at. Asbestos were all in millers. Within Thetford Mines, case-referent analyses showed a substantially increased risk associated with years of employment in a circumscribed group of five mines (Area A), but not in a peripherally distributed group of ten mines (Area B); nor was the risk related to years employed at Asbestos, either at the mine and mill or at the factory. There was no indication that risks were affected by the level of dust exposure. A similar pattern in the prevalence of pleural calcification had been observed at Thetford Mines in the 1970s. These geographical differences, both within the Thetford region and between it and Asbestos, suggest that the explanation is mineralogical. Lung tissue analyses showed that the concentration of tremolite fibres was much higher in Area A than in Area B, a finding compatible with geological knowledge of the region. These findings, probably related to the far greater biopersistence of amphibole fibres than chrysotile, have important implications in the control of asbestos related disease and for wider aspects of fibre toxicology.     

Clinical and epidemiological findings during a measles outbreak occurring in a population with a high vaccination coverage

Malignant mesothelioma is caused almost exclusively by occupational exposure to asbestos. During the past few years, however, increasing evidence has mounted that background exposure to asbestos could be sufficient to cause mesothelioma. Treatment of malignant mesothelioma remains a big problem. Some new approaches are on their way, and the most exciting ones are local immunotherapy in very early cases. Some success has been reported with local interferon treatment. As for treatment of metastatic pleural disease, the main purpose is symptomatic relief of dyspnea caused by fluid accumulation. The best way to achieve a lasting palliation is pleurodesis, and the most common way to do this, is by chemical means. The drug of choice in the United States has for many years been tetracycline, but since injectable tetracycline is no longer available, some substitute must be found. The substance that will "win" is not yet clear, but the two leading contestants are talc and doxycycline. Bleomycin also has its supporters, and a dark horse is quinacrine, which although not easily available in the United States, has been used in many European centers for decades.     

Actions of nitric oxide on renal epithelial transport

A 55-year-old male who had a remote history of occupational asbestos exposure consulted us because of chest pain. Chest X-ray revealed diffuse pleural thickening and pleural effusion on the right. A diagnosis of malignant mesothelioma, biphasic type was made by needle pleural biopsy. Fourteen months later, the patient died of brain metastasis. At autopsy, malignant mesothelioma of the pleura with metastasis to the brain and bilateral adrenal glands was observed. Brain metastases proven by autopsy are rare in cases of malignant mesothelioma. The ferruginous body count in the lung tissue was 16 per gram of wet weight.     

Asbestos in the lungs of persons exposed in the USA

Tissues obtained at autopsy or biopsy from 81 workers and 2 household persons, were chemically digested. The asbestos fibres recovered were characterized by analytical transmission electron microscopy. Among the 83 causes of death were 33 mesotheliomas, 35 lung cancers, 12 asbestosis and 3 from other cancers. Of the three major commercial asbestos fibre types, amosite was found to be the most prevalent fibre, occurring in approximately 76% of the cases, followed by chrysotile in approximately 60% and crocidolite in approximately 24%. Amosite and chrysotile were observed as the single commercial fibre in approximately 22 and approximately 17% of the cases respectively, whereas crocidolite and tremolite were found as the single fibre type in only approximately 2.5% of the cases. Among the fifteen cases where chrysotile and tremolite occurred together, the amount of chrysotile fibre always exceeded tremolite. However, tremolite was also found in ten additional cases where chrysotile was not detected. Amosite was present in four, amosite plus crocidolite in three, and crocidolite alone in one. Amosite was present in all of the insulation workers' lungs studied and was found in the highest concentration in this exposure category. The highest chrysotile concentration was found among workers in general trades. Although most prevalent in shipyard workers lungs, crocidolite concentration is not statistically different among the exposure groups studied. Although crocidolite was found in twenty cases, amosite accompanied it in eighteen of these. Eleven of the 20 cases were from shipyard workers. Of the 8 mesothelioma cases, 7 also contained amosite. Crocidolite alone only occurred in 1 of the 33 mesothelioma cases analysed. We concluded the following: crocidolite exposure occurred among USA insulators and a large percentage of other workers as well; insulation workers are primarily exposed to amosite; mixed fibre exposures are associated with more mesotheliomas than single fibre exposures; chrysotile only exposure is associated with approximately 12% of the mesothelioma cases studied; and if tremolite exposure is associated with chrysotile exposure, the chrysotile amount exceeds that for the associated tremolite.     

Management of a short femur discovered via ultrasound in utero. Prenatal diagnosis of Stuve-Wiedemann syndrome

BACKGROUND: Malignant mesothelioma reportedly shows different epidemiology and pathology in females, and a proportion are believed to arise spontaneously. METHODS: One hundred and seventy seven cases of malignant mesothelioma in females were reviewed, examined by histochemistry and immunohistochemistry, assessed for asbestosis and lung fibre burden by transmission electron microscopy with energy dispersive x ray analysis, and compared with 31 female controls. RESULTS: Two of one hundred and three cases tested for carcinoembryonic antigen were positive and were excluded from further analysis. Tumour cases showed increased amphibole burdens; in those in whom exposure information was known, 74 (80%) of 93 patients had a history of exposure to asbestos. Seventy two (47%) of 152 patients had lung fibrosis. Tumour site and histological type were little different from those reported in adult males. Mixed type histological pattern, lung fibrosis, and peritoneal site were associated with heavier lung asbestos burdens, but not exclusively. Thirty five (30%) of 117 patients had amphibole burdens of less than 2 x 10(6) fibres/g; the sites affected and the histological pattern of tumours in this group were similar to those in cases with amphibole fibre counts of > or = 2 x 10(6)/g lung. A higher lung amphibole burden than the mean burden in control females was found in 115 (98%) of 117 patients tested. CONCLUSIONS: The pathology of malignant mesothelioma appears to be similar in women and in men, and in cases associated and unassociated with asbestos.     

Exposure-response analysis of risk of respiratory disease associated with occupational exposure to chrysotile asbestos

OBJECTIVES: To evaluate alternative models and estimate risk of mortality from lung cancer and asbestosis after occupational exposure to chrysotile asbestos. METHODS: Data were used from a recent update of a cohort mortality study of workers in a South Carolina textile factory. Alternative exposure-response models were evaluated with Poisson regression. A model designed to evaluate evidence of a threshold response was also fitted. Lifetime risks of lung cancer and asbestosis were estimated with an actuarial approach that accounts for competing causes of death. RESULTS: A highly significant exposure-response relation was found for both lung cancer and asbestosis. The exposure-response relation for lung cancer seemed to be linear on a multiplicative scale, which is consistent with previous analyses of lung cancer and exposure to asbestos. In contrast, the exposure-response relation for asbestosis seemed to be nonlinear on a multiplicative scale in this analysis. There was no significant evidence for a threshold in models of either the lung cancer or asbestosis. The excess lifetime risk for white men exposed for 45 years at the recently revised OSHA standard of 0.1 fibre/ml was predicted to be about 5/1000 for lung cancer, and 2/1000 for asbestosis. CONCLUSIONS: This study confirms the findings from previous investigations of a strong exposure-response relation between exposure to chrysotile asbestos and mortality from lung cancer, and asbestosis. The risk estimates for lung cancer derived from this analysis are higher than those derived from other populations exposed to chrysotile asbestos. Possible reasons for this discrepancy are discussed.     

Hepatozoon canis infection of wild carnivores in Brazil

This paper describes a practical experience which took place in a Health District of the Lombardy Region (Northern Italy). This experience was motivated by the publication, on a newspaper, of the results of an epidemiological study which reported the nationwide geographical distribution of the mortality data for pleural mesothelioma during the period 1980-1987. The presence of excesses of pleural mesothelioma cases in two municipalities of Health District captured the attention of some field operators which decided to start working on the topic. Using all information available in the District all cases of pleural mesothelioma occurring during the period 1978-1993 in the two municipalities were identified; possible sources of both occupational and environmental asbestos exposure in the area were identified; and the next-of-kin of the cases was interviewed so as to gain information on the history of possible exposure to asbestos of the cases. For thirteen (out of seventeen) deaths the next-of-kin accepted to be interviewed and for them results are reported: the information presented describes gender, smoking habits, and an evaluation of the potential for exposure to asbestos both of occupational and environmental origin. We discuss the value importance of the experience, with particular emphasis on: a) the routine activities of the Services participating in the study; b) the resources employed; c) the use of epidemiological methods and tools; d) the primary prevention activities originated in the area; e) the personal motivations hat such experiences are capable to convey.     

The significance of asbestos exposure in the diagnosis of mesothelioma: a 28-year experience from a major urban hospital

A continued increase in the incidence of diffuse mesothelioma has been attributed to greater industrial use of asbestos but is also due in part to wider acceptance of this tumor by pathologists. In this retrospective study, the epidemiology, clinical presentation, and pathology of asbestos and non-asbestos-related mesothelioma from a major urban hospital were reviewed. Of the 36 cases of mesothelioma on file, 19 were not associated with exposure to asbestos. Although a retrospective study raises the possibility of inadequate occupational histories, the lack of history of asbestos exposure correlated with postmortem histology by light microscopy. When postmortem material was reviewed, evidence of asbestos exposure was present in all cases of mesothelioma with history of exposure to asbestos, and in no cases in which the patient denied history of asbestos exposure. Using strict histologic and histochemical criteria, the diagnosis of mesothelioma was confirmed in 8 of 9 patients with asbestos-related mesothelioma but in only 4 of 13 cases of non-asbestos-related mesothelioma. The diagnosis of diffuse methelioma is often difficult to make even wtih complete autopsy examinations. It should be entertained only with adherence to strict clinical and pathologic criteria, especially in women with no history to exposure to asbestos dust.     

Epidemiologic survey of pleural plaques among inhabitants of Matsubase exposed to asbestos

A high prevalence of pleural plaques (41.5%, 148/357) was found during a mass screening for lung cancer in Matsubase town in 1988. The inhabitants of this town were carefully studied each year from 1988 to 1993. The vast majority (81.2%) of inhabitants over the age of 20 years underwent chest roentgenography at least once during this period. Pleural plaques were detected by CT in 938 subjects, which is 17.3% of those studied and 4.1% of the total population. A total of 89 had an occupational history of asbestos exposure, 64 (71.9%) of whom had pleural plaques. However, these subjects with occupational exposure accounted for only 6.8% of the 938 subjects, and therefore most of the pleural plaques seemed to have been caused by general environmental exposure. The incidence of plaques was greater in older subjects: among those in the seventh decade of life it was more than eight times higher than among those in the fourth decade of life. Anthophyllite was detected in the main asbestos mill. The concentrations of asbestos fibers in the air and water near the old asbestos mills and factories were not high. The death rates and the adjusted mortality rates due to lung cancer in Matsubase were lower than in surrounding towns and lower than in Kumamoto prefecture as a whole. These results indicate that there is now no environmental contamination by asbestos fibers in Matsubase town. No cases of malignant mesothelioma have been confirmed in this town during the past 17 years.     

Environmental fibrous zeolite (erionite) exposure and malignant tumors other than mesothelioma

We studied the mortality in three villages in the Cappadocian region of Central Anatolia, Karain, Tuzk?y, and Sarihidir, which were exposed to fibrous zeolite (erionite), a known carcinogen more potent than the amphibole asbestos. Between 1970 and 1994, there were 305 deaths in Karain, and 177 (58%) were cancer related, including 150 (49.2%) malignant pleural mesothelioma, seven (2.3%) malignant peritoneal mesothelioma, and six (1%) gastroesophageal carcinoma. Four deaths (1.3%) from lung cancer included two nonsmoking females. There were three cases (1%) of leukemia and six of other malignancies (1.9%). Between 1980 and 1994, there were 519 deaths in Tuzk?y (T) and Sarihidir (S) (T = 432, S = 87). Of these, 257 were cancer related, and included 120 cases of malignant pleural mesothelioma and 64 cases of malignant peritoneal mesothelioma. Intraabdominal carcinoma was noted in 29 patients and 14 patients had lung cancer (four of whom were nonsmoking women). There were five cases of gastroesophageal cancer, five deaths due to leukemia, and 16 cases of various malignancies. These mortality figures support the hypothesis that erionite fibers cause cancer other than mesothelioma and lung cancer. Mineralogic analyses of the tissues should be performed to demonstrate this relationship.     

Epidemiology of chronic, precancerous and oncologic diseases in workers of asbestos and cement industry

Hygienic, clinical and epidemiologic screening was performed in staff of asbestos and cement goods production enterprise. Various dystrophic processes of pharynx and nasal cavity appeared to prevail among upper respiratory tract diseases. Average exposure to dust during 22 years at the stated production can lead to asbestosis 0-I stage, average exposure during 20.5 years can result in dust bronchitis and occupational allergic dermatosis can result from average exposure to dust during 21 years. Retrospective cohort study of mortality within 1949-1988 failed to find oncologic risk in workers engaged into asbestos and cement goods production higher than in general population.     

Survival of asbestos insulation workers with mesothelioma

Malignant mesothelioma is a lethal disease. It is rare in the general population; however, workers exposed to asbestos suffer significant burdens of the neoplasm. The survival time of 457 consecutive fatal cases of pleural and peritoneal mesothelioma that occurred among 17,800 asbestos insulation workers observed prospectively from 1 January 1967 to 1 January 1987 was studied. Mean survival time from initial presentation of the disease to death was 11.4 months for the pleural mesothelioma patients compared with 7.4 months for the peritoneal group. This difference was statistically significant. Mean survival time from diagnosis to death was shorter for both groups of patients: 8.4 months for pleural mesothelioma v 5.8 months for the peritoneal cases. In conclusion, survival time in mesothelioma patients is short; most die within a year from the onset of the initial symptoms. No effective therapy is yet available.     

European multicentric case control study on risk for mesothelioma after non-occupational (domestic and environmental) exposure to asbestos

The paper presents the European multicentric case-control study on risk for mesothelioma after non-occupational (domestic and environmental) exposure to asbestos. The study includes eight centres in seven European countries (Belgium, Denmark, Greece, Italy, Spain, Sweden and Switzerland). It is focused on the measurement of mesothelioma risk in relation to low intensity exposure to asbestos and to exposure to MMMF and other agents. It includes incident cases of pleural malignant mesothelioma (histologically diagnosed and verified) and a random sample of the population.     

Occupational and geographical factors in the epidemiology of malignant mesothelioma

In most industrialised countries mortality from malignant mesothelioma has risen steeply since about 1950 and is likely to go on doing so well into the next century. This increase, which has lagged behind the level of asbestos use by some 30 or more years, is most evident in men but less clear in women. Amphibole asbestos fibre types, crocidolite in particular, carry the greatest risk and chrysotile the least. Studies in chrysotile miners and millers, in whom the overall frequency of mesothelioma is low suggest the risk is mainly determined by the presence of contamination with amphibole fibres in the tremolite series. There is wide variation in mesothelioma incidence geographically and occupationally. Regions with the highest rates are those where crocidolite is mined; within countries, dockyard areas are most affected, probably because of amphibole use for insulation in naval ships. Occupations at high risk, apart from crocidolite miners and millers, include shipyard and insulation workers and those employed in construction trades. Data on exposure-response are scanty although occupational cohort studies suggest that risk is related to both duration and intensity of exposure. More specific confirmation of an exposure-response relationship has been obtained from lung fibre analysis in a limited number of case-referent studies.     

Antimicrobial properties of human lysozyme transgenic mouse milk

To examine whether malignant mesothelioma due to asbestos has genetic alterations in the Ha- and Ki-ras oncogenes or in the p53 suppressor gene, we analyzed the point mutations of these genes in paraffin-embedded autopsy samples of the primary tumors of malignant mesothelioma in seven asbestos patients who died from malignant mesothelioma. The genetic analysis was conducted by the polymerase chain reaction-single strand comformation polymorphysms (PCR-SSCP) method in all patients, and through the sequencing of deoxyribonucleic acid (DNA) bases in one patient. No genetic alterations were found in exons 1 or 2 of Ha- and Ki-ras oncogenes, or in exons 5 to 9 of the p53 gene, in any of the patients. Further studies on a larger number of patients are required to reach a definite conclusion concerning the genetic effects of asbestos on malignant mesothelioma.