WORK ENVIRONMENTS--especially in asbestos-processing factories--have improved since the health hazard of asbestos exposure was ascertained; therefore, one would expect that the numbers of asbestosis cases with severe fibrosis would decrease. The available data are inadequate for the evaluation of whether the total number of asbestosis cases, including those with mild and moderate fibrosis, is, in fact, decreasing. In Japan, most asbestos is imported, and domestic consumption of asbestos has increased markedly subsequent to World War II. Approximately 0.20-0.35 million tons of asbestos have been used each year for the past 25 y. Presently, Japan is one of the leading asbestos-consuming countries in the world. Although there is a long latency period until pulmonary fibrosis and other asbestos-related diseases are manifested, considerable time has elapsed since large amounts of asbestos came into use in Japan.
Asbestosis is frequently accompanied by malignant tumors, such as lung cancer and malignant mesothelioma. There is a general consensus that a cause-and-effect relationship exists between asbestos exposure and these two malignancies. In addition, the results of epidemiologic studies have suggested that an association exists between asbestos exposure and other malignancies--including those involving the gastrointestinal tract, larynx, and hematopoietic systems.[2,3]
In this statistical study, we investigated the demographic transition of the frequency of asbestosis in autopsy cases. We then compared the frequency of malignant tumors in the cases with asbestosis with the frequency in the nonasbestosis cases.
Materials and Method
Subsequent to 1958, autopsy cases in Japan have been registered in the Annual of the Pathological Autopsy Cases in Japan by the Japanese Society of Pathology. At the time the 1996 annual was issued, a total of 525 (484 male, 38 female, 3 unknown) asbestosis cases had been recorded among 1,056,259 autopsy reports. Age, sex, clinical diagnosis, residence area, occupation, main pathological lesions, and some additional lesions were recorded for each case in the annual. Malignant tumors are generally regarded as the main pathological lesions--independent of tumor size. To evaluate the frequency of malignant tumors, we used some of the statistical data provided in the appendix of the annual.
Diagnostic criteria for asbestosis in the United States, which were reported by the Pneumoconiosis Committee of the College of American Pathologists and the National Institute for Occupation and Safety and Health in 1982, were the demonstration of discrete foci of fibrosis in the walls of respiratory bronchioles, with associated accumulations of asbestos bodies. In Japan, most autopsy cases with asbestosis have been diagnosed under the following three criteria: (1) history of occupational asbestos exposure, (2) presence of asbestos bodies in histologic section(s), and (3) presence of diffuse interstitial pulmonary fibrosis. The diagnosis of asbestosis is straightforward when all of the three conditions are met; however, if the diagnosis is made based only on the latter two criteria, the core fiber's of the bodies should be analyzed. Based on our experience and our evaluation of reported data, we believe that there are few cases with diffuse interstitial fibrosis caused by other mineral fibers in Japan. Therefore, we believe the frequency of false-positive cases among the cases cited in the annual would be low. However, given that most cases have been diagnosed on the basis of the presence of diffuse interstitial fibrosis, some asbestosis cases with low-grade fibrosis might have been overlooked.
We were unable to obtain information on asbestos exposure level for each patient, because the patients were located all throughout Japan. We examined the frequency of asbestosis in autopsy cases during each of the three time periods--1958-1979 (22 y), 1980-1989 (10 y), and 1990-1996 (7 y)--as well as across the three time periods. We used the Chi-square test and the Kruskal-Wallis test in the statistical analyses.
The frequency of asbestosis (number of cases/total number of autopsy cases) was 0.050% (525/1,056,259) for the entire 39-y period spanning 1958-1996 (Table 1). The comparison across the three time periods studied revealed a significant increase in the frequency of asbestosis, from 0.017% (76/440,334) in 1958-1979 to 0.058% (226/390,124)in 1980-1989, and, finally, to 0.099% (223/225,801) in 1990-1996 ([chi square] = 207.993, p [is less than] .0001). Approximately 1 asbestosis case per 1,000 autopsy cases was found in the most-recent 7-y period.
(*) Number within parentheses is the number(s) of case(s) for whom sex designation was not available.
([dagger]) [chi square] = 207.993, p < .0001.
The average age at death for asbestosis cases in each period studied is shown in Table 2. The average age increased aross the three terms, from 58.4 y (1958-1979) to 64.0 y (1980-1989) to 67.4 y (1990-1996) (p [is less than] .0001).
(*) p < .0001 (Kruskal-Wallis test).
([dagger]) The ages of two men in the 1990-1996 time period are not described.
The number of asbestosis cases in the 8 geographical regions of Japan (illustrated in Fig. 1 [i.e., Hokkaido, Tohoku, Kanto, Chubu, Kansai, Chugoku, Shikoku, and Kyushu]) are shown in Table 3. The numbers of cases were highest in the Kanto and Kansai regions. For the time period 1958-1979, 53.9% of all asbestosis cases occurred in the Kansai region, but the proportion declined after 1979.
[Figure 1 ILLUSTRATION OMITTED]
Table 3.--Numbers of Asbestosis Cases in Eight Regions of Japan
We categorized, by occupation, the cases with asbestosis into three groups: (1) employed in processing plants, (2) employed in occupations that involved exposure to asbestos products, and (3) employed in an area for which there were unknown asbestos source(s) or employed in an occupation not described in the annual (Table 4). In approximately 40% of the cases, the asbestos source could not be identified. The proportion of subjects employed in occupations that involved asbestos products increased across the three time periods, and there was a concomitant decrease in the proportion of individuals employed in processing plants. Among the 150 subjects who were employed in occupations that involved exposure to asbestos products, 45 had been employed as shipyard workers, 43 as construction workers, 18 as steel mill workers, 15 as pipe fitters, 11 as asbestos insulation workers, 7 as electricians, 5 as railroad workers, 3 as boiler-room workers, and 3 as air-conditioning specialists.
Notes: Category 1 = worker in a processing plant; category 2 = worker dealing with asbestos products (e.g., shipyard worker, worker in the construction industry, steel-mill worker, insulation worker, electrician, pipefitter, railroad worker, boilerman, air-conditioner worker); and category 3 = worker exposed to unknown asbestos source.
(*) Number within parentheses is the number of cases for whom occupational history was not described in the annual.
The proportion of asbestosis cases who had worked in processing factories (i.e., category 1) was high in the Kansai region (Table 5), whereas the proportion of cases who had dealt with asbestos products (i.e., category 2) was high in other regions. In many asbestosis cases there was a history of working in processing factories in Osaka and Nara Prefectures in the Kansai region. Some cases, however, were identified in areas where the ship-building industry has developed (e.g., Yokosuka City in the Kanto region, along the Inland Sea in the Chugoku region, Nagasaki City in the Kyushu region).
Table 5.--Numbers of Asbestosis Cases in Eight Regions of Japan, by Occupational Category
Notes: Category 1 -- worker in a processing plant; category 2 = worker dealing with asbestos products (e.g., shipyard worker, worker in the construction industry, steel-mill worker, insulation worker, electrician, pipefitter, railroad worker, boilerman, air-conditioner worker); and category 3 = worker exposed to unknown asbestos source.
Malignant tumors associated with asbestosis are listed in order of frequency in Table 6. Multiple cancers were counted separately in the calculation. Malignant tumors were found in 61.0% (320/525) of the asbestosis cases, and the frequency increased across the three time periods, from 43.4% (1958-1979) to 62.8% (1980-1989) to 65.0% (1990-1996). The increasing tendency is remarkable in mesothelioma. The frequency of mesothelioma in 1990-1996 was about three times the frequency during 1958-1979. Frequency of lung cancer, however, did not increase appreciably across the three time periods. In total, there were 174 lung cancers (33.1%), 44 malignant mesotheliomas (13.9%), 29 stomach cancers (5.5%), 14 liver cancers (2.7%), 9 prostatic cancers (1.7%), 8 malignant lymphomas (1.5%), 6 laryngeal cancers (1.1%), 4 pancreas cancers (0.8%), 3 rectal cancers (0.6%), and 28 other cancers (5.3%).
Table 6.--Types of Malignant Tumors Associated with Asbestosis
(*) Two types of cancer in 15 cases and three types of cancer in one case.
([dagger]) Two types of cancer in 11 cases.
For all of the 1,055,734 nonasbestosis autopsy cases, the frequency (number of cases) of lung cancer, mesothelioma, and laryngeal cancer was 8.6% (90,914), 0.2% (1,773), and 0.3% (3,230), respectively (Table 7). The frequency of each of these three diseases in the asbestosis cases was significantly higher than that in the nonasbestosis cases. For other malignancies, there was no difference between the frequency of occurrence in the asbestosis and nonasbestosis cases.
Table 7.--Frequency of Lung Cancer, Mesothelioma, and Laryngeal Cancer in Asbestosis and Nonasbestosis Cases
(*) [chi square] = 400.7, p < .0001.
([dagger]) [chi square] = 5,675.6, p < .0001.
([double dagger]) [chi square] = 12.0, p < .001.
([sections]) Tracheal cancers are included in lung cancer data for nonasbestosis cases.
During the entire time period studied, the number of asbestosis cases increased among individuals who had occupational histories of working with asbestos products, as well as among individuals who had been employed in asbestos-processing plants. During the initial 22 y (1 958-1979), about one-half of the asbestosis cases had such an occupational history in the Kansai region. Many small-scale textile factories were in operation in Kansai, and the working conditions were not satisfactory at that time. In addition, the numbers of asbestosis cases for which there was an occupational history of dealing with asbestos products increased throughout all of Japan. Some cases occurred in ship-yard workers; others occurred among workers in the construction industry, including asbestos insulation workers, welders, and individuals who specialized in air-conditioning work. In Japan, the consumption of asbestos is greatest in the construction industry. In addition, some cases occurred in railroad workers, especially in mechanics in steam-locomotive factories. In a previous study, we reported that, of 27 malignant mesothelioma cases, 1 had been a shipyard worker, 3 had worked in the construction industry, and 4 had worked on the railroad.
Although the working conditions in processing factories have improved in recent years, the frequency of asbestosis has not decreased. The age at death of asbestosis cases has increased, and the number of cases among workers dealing with asbestos products has increased. Based on these results and our experience, we speculate that there has been a recent increase in the number of cases with mild and moderate fibrosis, although the intensity of the fibrosis was not described in most cases included in the annual. If one assumes that there has been a reduction in asbestos exposure levels in asbestos-processing plants, it is logical to assume that development of fibrosis will require additional time.
Approximately 60% of the asbestosis cases had accompanying malignant tumors, of which lung cancer, followed by malignant mesothelioma, occurred most frequently. There are many risk factors, such as cigarette smoking, for lung cancer. Conversely, there are few risk factors other than asbestos exposure for mesothelioma. Therefore, mesothelioma is the asbestos-related tumor on which investigators place great focus. However, it is likely that the actual number of asbestos-related lung cancer cases is higher than for asbestos-related mesothelioma. We consider lung cancer cases with asbestosis to be asbestos-related, but if asbestosis is absent, it is not a simple matter for us to evaluate the relationship between asbestos and lung cancer cases. According to our own criteria, cases for which the three criteria have been met (a) occupational history of asbestos exposure are obvious, (b) asbestos bodies are detected in histologic section(s), and (c) more than 10,000 asbestos bodies per 5 g wet lung tissue are found can be considered asbestos-related lung cancer.[7,8] Conversely, as we reported previously, more than 100,000 asbestos bodies were found in 5 g wet lung tissue in 5 of 7 asbestosis cases.
It is noteworthy that the number of cases of malignant tumors with asbestosis has increased year by year. We speculate that this increase may be connected with asbestos exposure levels. Given the reduction of asbestos exposure levels in processing plants, the number of deaths from only fibrosis has decreased, but after the long latency period, malignant tumors are more likely to be produced.
The frequency of mesotheliomas with asbestosis increased the most across the three time periods, but lung cancers did not increase concomitantly. We can attribute this fact to the asbestos exposure levels, and we speculate that there may be different asbestos exposure levels that produce these different tumors; mesothelioma might be produced at lower exposure levels than those that produce lung cancer. Moreover, there may be different latency periods for the two malignancies, with mesothelioma requiring a longer latency period than lung cancer. In addition, perhaps these two processes act in combination. We cannot, however, exclude the possibility that pathologists have been more focused on the relationship between asbestos and mesothelioma, rather than on the relationship between asbestos and lung cancer, with resulting bias of the data concerning fibrosis and asbestos bodies.
Although lung cancer and mesothelioma are asbestos-related tumors, controversy lingers regarding malignancies at other sites. Laryngeal cancer is one such tumor. Studies indicating positive and negative results for this relationship have been reported. We did not evaluate smoking habits and alcohol consumption--both of which are considered to be other risk factors--but our data suggested an association of laryngeal cancer with asbestos exposure. We need more data before we can arrive at a firm conclusion regarding this problem.
In Japan, large amounts of asbestos have been used continuously for more than 40 y--until recently when the import of amphibole asbestos was banned completely. Therefore, the number of cases of malignant tumors related to asbestos exposure will almost certainly increase for at least 20 y.
The authors thank all those who contributed to the Annual of the Pathological Autopsy Cases in Japan.
Submitted for publication May 15, 1999; revised; accepted for publication November 26, 1999.
Requests for reprints should be sent to Dr. Yoshihiro Murai, Department of Pathology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, 930-0194 Japan.
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YOSHIHIRO MURAI MASANOBU KITAGAWA Department of Pathology Faculty of Medicine Toyama Medical and Pharmaceutical University Toyama, Japan
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