Document 6RL1DeM1R8zpaV42G7DDM2yYo

Industrial Health 2000, 38, 301-308 Original Article Asbestos Exposure in a Shipyard Area, Northeastern Italy Claudio BIANCHI*, Alessandro BROLLO and Lucia RAMANI Laboratory of Pathological Anatomy, Hospital of Monfalcone, 34074 Monfalcone, Italy Received March 14, 2000 and accepted May 31, 2000 Abstract: The Monfalcone area, northeastern Italy, is a small industrial district (population 60,000), with a large shipyard. In order to monitor asbestos exposure in this area, a series of 3,640 necropsies, carried out at the Monfalcone Hospital between October 1979 and September 1998, were investigated. The thoracic cavities were examined for pleural plaques; these were classified into three classes (small, moderate, large). Routine histological sections of lung tissue were examined for asbestos bodies. Isolation and counting of asbestos bodies were performed in 1,075 cases. Lifetime occupational data were collected in 1,277 cases. Pleural plaques were observed in 70.5% among men and in 23.8% among women. The prevalences of pleural plaques did not show significant variations during the study period. Asbestos bodies were found on routine lung sections in 23.7% of men and 3.0% of women. The shipyard workers, the most numerous category in the series, were characterized by high prevalence of pleural plaques (total 86.7%, large 32.4%), high prevalence of asbestos bodies on routine lung sections (35.3%), and high amounts of lung asbestos bodies after isolation. The present data indicate that asbestos exposure may reach alarming levels in the shipyard areas. Key words: Asbestos exposure, Asbestos bodies, Pleural plaques, Shipbuilding, Necropsy Introduction A lot of data indicate that asbestos exposure and its effects have become major health problems in the industrial world: (1) the incidence of malignant mesothelioma, a sentinel event of the asbestos exposure, shows a dramatic increase in various industrialized countries1-3*; (2) the number of the occupational categories at risk for asbestos disease is increasing4); (3) the results of recent investigations confirm that the risk of asbestos-related mesothelioma persists at low doses1*; (4) some studies conducted in the United States5* and in Italy6* suggest that in the areas with asbestos industries, the risk involves all people resident in the area; (5) in many countries, the use of asbestos continues, in other this use has been stopped in the 1980's or in the 1990's. Given the fact that the latency periods in asbestos-related mesothelioma are frequently higher *To whom correspondence should be addressed. than 40 years7), mesothelioma will represent a serious problem in the next decades, even in the countries where asbestos has been prohibited. A recent analysis predicts that some 250,000 deaths from mesothelioma have to be expected among men of Western Europe over the next 35 years8*; (6) some investigations show that in certain occupational groups, such as the petrochemical industry workers9*, asbestos-cement workers10*, and shipyard workers11*, the proportion of lung carcinomas attributable to asbestos may reach very high percentages (50-70%*. In this context it is opportune: a* to monitor exposure to asbestos in the general population; b* to identify the groups at higher risk; c* to try all the ways in order to neutralize the effects of asbestos among the subjects heavily exposed to asbestos in the past. The present study, an extension of previous investigations12*, has been performed in the Monfalcone area. This area is a 302 C BIANCHI et al. small industrial district, with a total population of about 60,000 inhabitants, located in northeastern Italy at the border with Slovenia. Monfalcone is called the "shipyard town". A shipyard was opened here in 1907. In the following decades the Monfalcone shipyard became the most important shipbuilding installation in the Mediterranean region. The workforce of the shipyard strongly increased in the 1930's, when the number ofworkers passed from 2,000 to over 5,000. Moreover in the Monfalcone shipyard, electromechanic shops and aereonautic works were located, employing additional 4-5,000 people. In the 1950's the total number of shipyard workers was about 6,000, and decreased to 3,500-5,000 in the 1960's and 1970's. The above figures indicate that in the Monfalcone area a majority of the male population has spent some part of their worklife in the shipyard. In the past asbestos has largely been used in the shipbuilding industry7*. In the present investigation, three indicators of asbestos exposure (occupational history, pleural plaques, and lung asbestos bodies) were examined in a large necropsy series. by routine methods were histologically examined for the presence of asbestos bodies. In 1,075 cases isolation and counting of lung asbestos bodies were performed, after chemical digestion of a sample obtained from the right base13). In 1,277 cases lifetime occupational histories were obtained from the patients' relatives by personal interviews. Statistical analysis was performed by Epi Info, version 5, from the Centers for Disease Control (Atlanta, GA). The chi-square test was used to compare the prevalences of pleural plaques and those of asbestos bodies in the various groups. The relationship between pleural plaques and presence of asbestos bodies in lung sections was analyzed by the chisquare test for linear trend. The relationships among the various occupations and the asbestos body amounts in digested lung tissue were examined by ANOVA test or by Mann-Whitney two-sample test, after Bartett's test for homogeneity of variance. Results Materials and Methods During the period October 1979-September 1998, 3,685 necropsies were performed at the Hospital of Monfalcone. The 3,640 necropsies carried out in persons aged 15 years or more were included in the study. The necropsies represented percentages ranging between 30 and 45 of the hospital deaths among men, and 20-30% of the deaths among women. In each case the thoracic cavity was carefully examined for pleural plaques. All white ivory patches, unilateral or bilateral, calcified or not, involving parietal pleura were considered as pleural plaques. The plaques were classified into three classes: 1, small; 2, moderate; and 3, large, on the basis of the size of the plaque. Class 1 included the cases with small plaques (1-4 cm in major diameter); class 2 comprised plaques larger than 4 cm in major diameter, but not involving a majority of a hemithorax; class 3 corresponded to cases with plaques involving the majority of a hemithorax. When the two pleural cavities differed one from the other (one side only being involved by the plaques, or both sides being involved, but at different degrees), the classification of the case was based on the aspect of the involved, or of the more seriously involved, side. In a majority of cases one or more samples obtained from the pleura involved by the plaques, were histologically examined by the routine methods (paraffin inclusion, hematoxilyn-eosin staining). In all the cases some sections of lung tissue, processed The prevalence of pleural plaques was high among men aged 35 years or more, with small variations from one age group to another (Table 1). Among women there was a progressive increase in the prevalence of pleural plaques from the age group 35-44 years to the group 55-64, with stationary values in the decade 65-74, and decreasing figures in the oldest groups. There were strong differences between the sexes in the prevalences of total plaques (p<0.0001) as well in the prevalences of large plaques (p<0.0001). Men resident in the Monfalcone area differed in the prevalence of total plaques (p<0.0001) and prevalence of large plaques (p<0.0001) from men resident in other places (Table 2). Among women there was a difference in the prevalences of total plaques (p<0.0001), and in the prevalences of moderate-large plaques (p<0.05). The analysis of residence places revealed that a large majority of people resident outside the Monfalcone district, lived in the immediately adjacent area. When autopsy cases were subdivided in six categories on the basis of age groups, and of calendar years, not relevant variations were noted (Table 3). Asbestos bodies were found on routine lung sections in 23.7% of men, and in 3.0% of women. Men resident in the Monfalcone area showed more frequently asbestos bodies than non-residents (p<0.0001) (Table 4). Among women the difference did not reach the statistical significance. The two sexes differed in the prevalence of lung asbestos body amounts, women very rarely showing more than 10,000 Industrial Health 2000, 38, 301-308 ASBESTOS EXPOSURE IN A SHIPYARD AREA Table 1. Prevalence of pleural plaques in an autopsy series in Monfalcone, Oct. 1979-Sept. 1998, by sex and age group Age groups (years) 15-24 25-34 35-44 45-54 55-64 65-74 75-84 85-94 95 and over Total No. of cases Men Pleural plaques (%) Class 1 Class 2 Class 3 Total 5 12 49 165 399 707 709 207 7 2,260 0 0 18.4 18.2 23.8 25.2 22.1 22.7 42.9 23.0 0 8.3 22.4 24.2 25.3 29.7 30.3 27.1 0 28.1 0 0 18.4 23.0 20.1 17.8 21.3 17.9 0 19.5 0 8.3 59.2 65.5 69.2 72.7 73.8 67.6 42.9 70.5 No. of cases Women Pleural plaques (%) Class 1 Class 2 Class 3 Total 0 80 0 0 0 25 8.0 0 0 8.0 45 13.3 2.2 0 15.5 128 21.9 6.3 1.6 29.8 271 20.3 8.1 1.1 29.5 557 18.3 5.6 0.2 24.1 333 15.3 3.9 0.6 19.8 13 0 7.7 0 7.7 1,380 17.7 5.5 0.6 23.8 303 Table 2. Prevalence of pleural plaques in an autopsy series in Monfalcone, Oct. 1979-Sept. 1998, by residence status Place of residence Monfalcone area Other No. of cases Men Pleural plaques (%) Class 1 Class 2 Class 3 Total 1,940 22.8 29.5 21.4 73.7 320 23.8 19.4 8.1 51.3 No. of cases Women Pleural plaques (%) Class 1 Class 2 Class 3 Total 1,145 19.6 6.2 0.6 26.4 235 8.5 2.1 0.4 11.0 Table 3. Prevalence of pleural plaques in an autopsy series in Monfalcone, Oct. 1979-Sept. 1998, among subjects resident in the Monfalcone area, by period and age group Period No. of cases Men Pleural plaques (%) Class 1 Class 2 Class 3 Total Age 16-54 y. 1979-85 1986-91 1992-98 96 41 59 Age 55-110 y. 1979-85 1986-91 1992-98 602 465 677 22.9 7.3 16.9 21.9 26.8 20.3 25.0 17.1 23.7 69.8 51.2 60.9 24.6 21.7 23.5 24.3 36.1 31.6 25.9 18.5 18.9 74.8 76.3 74.0 No. of cases Women Pleural plaques (%) Class 1 Class 2 Class 3 Total 31 12.9 3.2 0.0 16.1 13 15.4 0.0 0.0 15.4 25 4.0 0.0 0.0 4.0 320 20.6 5.3 0.9 26.8 315 22.5 6.3 0.0 28.8 441 18.1 7.5 0.9 26.5 asbestos bodies/g dried tissue (Table 5). The prevalence of asbestos bodies on routine lung sections showed a marked and progressive increase passing from people without plaques to the various classes (1, 2, 3) of plaques (p<0.0001) (Table 6). The prevalence of asbestos exposure markers showed marked differences among the various occupational categories (Table 7). In particular, the shipyard workers showed significantly higher prevalences of moderate-large plaques (p<0.0001), and significantly higher prevalence of asbestos bodies on routine lung sections (p<0.0001) when compared with the other groups. The women classified as domestic exposure had cleaned the work clothes of their relatives, employed in the shipyard or in other industries. The shipyard workers showed higher amounts of lung asbestos bodies in digested lung tissue than the other groups (Table 8). In particular, the shipyard workers significanlty differed from the other categories in the percentage of cases with more than 104 asbestos bodies/g (p<0.0001). 304 C BIANCHI et al. Table 4. Prevalence of asbestos bodies in lung sections in an autopsy series in Monfalcone, Oct. 1979-Sept. 1998, by sex, age group, and residence status Age (years) 16-54 55-110 Men Residents No. of Positive cases (%) Others No. of Positive cases (%) 196 1,744 22.4 26.4 35 285 8.6 9.8 Women Residents No. of Positive cases (%) Others No. of Positive cases (%) 68 1,076 0.0 9 3.3 226 0.0 2.2 Table 5. Number of asbestos bodies isolated after chemical digestion of lung tissue from 1,075 autopsied cases, Monfalcone, Oct. 1979-Sept. 1998 Asbestos bodies* 0 101 102 103 104 105 106 Total Men No. of cases (%) 29 3.2 99 11.1 197 22.1 244 27.3 229 25.6 86 9.6 9 1.0 893 100 *No. of asbestos bodies/g dried tissue. Women No. of cases (%) 8 4.4 39 21.4 85 46.7 42 23.1 7 3.8 1 0.5 0 182 100 Table 6. Prevalence of asbestos bodies in lung sections and pleural plaques in an autopsy series in Monfalcone, Oct. 1979-Sept. 1998 Pleural plaques Absent Class 1 Class 2 Class 3 Total Men No. of cases Asbestos bodies (%) 666 519 634 441 2,260 4.8 14.1 32.6 50.8 23.7 Women No. of cases Asbestos bodies (%) 1,051 244 76 8 1,379 2.1 2.9 9.2 62.5 3.0 Table 7. Prevalences of pleural plaques and lung asbestos bodies in an autopsy series in Monfalcone, Oct. 1979-Sept. 1998, by occupational group Occupation Shipbuilding Dock and sailors Various Other industries Domestic exp. Negative ** Total No. of cases Pleural plaques (%) Class 1 Class 2 Class 3 Total 646 41 153 232 141 64 1,277 21.2 41.5 26.8 26.7 39.0 6.3 24.7 33.1 19.5 20.9 11.2 11.3 1.6 23.3 32.4 9.8 13.1 3.4 0.7 0.0 19.0 86.7 70.8 60.8 41.3 51.0 7.9 67.0 Asbestos bodies* 35.3 4.9 11.1 4.3 2.8 0.0 20.4 *Prevalence of asbestos bodies (%) on routine lung sections. "Occupational data negative for asbestos exposure. Discussion In the present study, asbestos exposure was investigated by analyzing three different parameters, occupational data, lung asbestos bodies, and pleural plaques. Each of such parameters has different degrees of sensitivity, and specificity. On the other hand, the reliability of the information these parameters may furnish, increases if two or three of them are simultaneously explored. Occupational history may clearly indicate that an exposure to asbestos has occurred. If the patient has worked as an insulator or if he or she has been employed in asbestos mining or in asbestos industries, there is no doubt about his or her exposure. However, frequently it happens that a person has Industrial Health 2000, 38, 301-308 ASBESTOS EXPOSURE IN A SHIPYARD AREA 305 Table 8. Numbers of asbestos bodies in digested lung tissue in an autopsy series in Monfalcone, Oct. 1979-Sept. 1998, by occupational group Occupation Shipbuilding Dock and sailors Various Other industries Domestic exp. Negative ** No data Total No. of cases 430 21 89 111 68 13 343 1075 Asbestos bodies (%** <103 103 104 105-106 21.4 57.1 51.7 68.5 66.2 69.2 51.6 42.5 29.5 38.1 33.7 24.3 30.9 30.8 20.1 26.6 33.5 4.8 12.4 4.5 2.9 0.0 21.3 22.0 15.6 0.0 2.2 2.7 0.0 0.0 7.0 8.9 *Number per gram dried lung tissue. **Occupational data negative for asbestos exposure. been indirectly exposed, as a bystander, and this fact does not always emerge from the occupational history. Moreover, in a lot of cases the patient has worked in a plant that has been closed since various decades. In this setting, it is extremely difficult or impossible, to assess on the only basis of the occupational data, whether or not the exposure has been occurred. However, a given occupational history becomes more easy to interpret, when also objective signs of asbestos exposure are available. The detection of asbestos in lung tissue is the most direct way of determining, if a given person has been exposed to asbestos. In addition, the examination of the lung for asbestos gives precious information on the intensity of the exposure. The examination of routine lung sections for asbestos bodies, adopted in the present study, is a rather rough method. The advantage is that it may be routinely applied in all the cases. However, several factors reduce the sensitivity of the method: asbestos bodies may be hidden by carbon pigment; asbestos bodies are not rarely irregularly distributed, being frequent in some sections and rare or absent in others; very small bodies are difficult to detect; chrysotile fibres frequently disappear from the lung tissue; there are individual differences in the tendency to form asbestos bodies, etc. Despite such limitations, asbestos bodies were found on routine lung sections in about 1/4 of the men resident in the Monfalcone area. Some of the above difficulties encountered in detecting asbestos bodies, may be surmounted by using isolation and counting of asbestos bodies after chemical digestion of the lung tissue. Countings of the bodies have been performed in a consistent portion of the present cases. More precise methods include the counting of the asbestos fibres and the identification of such fibres. This last point is of particular relevance, since the old question of the danger related to the chrysotile, continues to be discussed14-17*. The identification of the type of asbestos has been performed only in a very limited sample of the present series and the results have previously been published18*. The analysis conducted on lung tissue, mediastinal lymph nodes, and pleural plaques of people formerly shipyard workers, showed the presence of different varieties of asbestos. Interestingly, while amphyboles were the most prevalent fibres in lung, chrysotile was the most prevalent fibre in the pleura18*. Similar results on this different tropism of amphyboles and chrysotile have been obtained in other laboratories19, 20*. Pleural plaque has for longtime considered as late sequelae of tuberculosis. In the early 1960's, the idea emerged with difficulty that pleural plaque is the effect of an exposure to asbestos21*. A number of studies conducted in different settings confirmed the relationship asbestos-pleural plaque12, 22, 23*. It is relevant that pleural plaque is not only a marker of asbestos exposure, but also an indicator of the exposure intensity12*. In addition, pleural plaque is a marker by far more sensitive than the presence of asbestos bodies in routine lung sections. This clearly emerges from Table 6. In the present study the prevalence of pleural plaques was very high among men resident in the Monfalcone district. The male subjects resident in the sorrounding area showed a prevalence by far lower. However, such a population of the adjacent area may only partly be considered as a referent population. In fact, a part ofthe Monfalcone shipyard workers came, especially in the past, also from the surrounding area. A better term of comparison may be found in Gorizia, a town distant 25 km from Monfalcone and with a relatively small number of industrial installations. In a series of 100 consecutive necropsies examined at the Hospital of Gorizia in 1994, pleural plaques were observed in 19.6% among men, and in 5.1% among women24*. Moreover, some men with plaques of the Gorizia series had histories of working in the Monfalcone shipyards. The figures found in the Monfalcone area appear very high, even when compared with those found in other highly industrialized areas of northern Italy. A series of 100 necropsies were examined in the Venice area in 199225*. Such area is characterized by a high concentration of industries, including chemical, machinery, metallurgical. Pleural plaques were found in 37% of men, and in 6% of women. Isolation of lung asbestos bodies showed relatively low amounts of bodies (below 1,000 per gram of dried tissue* in all women, and in 94% of men. In northwestern Italy, a study conducted in Turin on 1,019 necropsies performed in 306 C BIANCHI et al. the period September 1977-May 1979, showed pleural plaques in 24.5% among men, and in 7% among women26). In Turin the highest prevalence of pleural plaques, namely 37.7%, was observed among men aged 60-69 years. When the data collected on pleural plaques, lung asbestos bodies, and on occupational histories, are considered as a whole, it emerges that the high degree of asbestos exposure in the Monfalcone area, has to be attributed mainly to the shipbuilding activity. In fact, although asbestos exposure has involved different occupational categories in the Monfalcone area, marked differences exist from one category to another in terms of exposure intensity. These differences mainly emerge, when some parameters are considered, such as the prevalences of asbestos bodies in routine lung sections, the prevalences of the complex moderate-large plaques, and the prevalences of large amounts of asbestos bodies (10,000 or more per gram) in digested lung tissue. These data clearly indicate that an important gradient existed in the past between asbestos exposure occurred in the shipbuilding, and that occurred in many other industrial activities. The present findings also indicate that asbestos exposure in Monfalcone did not remain confined to various workplaces; on the contrary the family members of the shipyard workers were involved at relevant degrees throughout the work clothes polluted by asbestos dust. The possibility that an important environmental exposure to asbestos, different from the domestic one, has occurred, is suggested by some cases; this point however requires further investigation. The severity of the asbestos exposure is not an unexpected finding in a shipyard area. The relationship between asbestos exposure and shipbuilding activity is well known. Such relationship was firstly recognized some 40 years ago. In 1958, McCaughey described a group of pleural mesotheliomas diagnosed in Belfast, Northern Ireland27). In the original description, no attention had been devoted to the occupational history of these patients. However, few years later, it was ascertained that a consistent portion of the Belfast cases were represented by shipyard workers28, 29). Subsequently, clusters of asbestos-related mesotheliomas were reported from many coastal areas with shipyards, and the relationship mesothelioma-shipbuilding was recognized as one of the most typical facts in the mesothelioma epidemiology7, 30-32). The relevance of asbestos-related pathology among shipyard workers has recently been emphasized by a study conducted in Japan33). In a group of 72 shipyard workers examined at necropsy, 86% showed asbestos-related conditions, including pulmonary asbestosis, pleural plaques, lung cancer, and malignant pleural mesothelioma. What are the implications of the present findings in terms of cancer risk for the population of the Monfalcone area? Studies performed during the last 20 years showed that the incidence of malignant mesothelioma in Monfalcone was among the highest in the world32, 34). As far as lung carcinoma is concerned, a recent analysis of 414 cases, investigated at necropsy in Monfalcone, showed that about 60% of the cases had to be attributed to asbestosu). In addition, studies conducted at our laboratory, indicate that pleural plaque may be considered as a risk indicator for asbestos-related mesothelioma of the pleura22) as well as for asbestos-related carcinoma of the lung35). The risk progressively increases by passing from small to moderate and from moderate to large plaques. This suggests that a population showing so high prevalences of moderate and large pleural plaques such those observed in the present study, is at high risk of pleural and pulmonary cancer. Of the two markers of asbestos exposure investigated in the present study, pleural plaque appears the more sensitive one. Pleural plaque is also a parameter more easy to investigate in vivo. Asbestos bodies may be detected in sputum, but only when the amount of asbestos is very high. On the contrary, pleural plaques, especially when moderate or large in size, are easy to reveal by imaging tecniques. The detection of pleural plaques may then represent a relevant method in screening people with not trivial exposure to asbestos and at risk for asbestos-related cancer22). Asbestos exposure has been reduced or stopped in many shipyards throughout the world. However, in the shipyard areas, large numbers of persons, severely exposed to asbestos in the past, remain at high risk for asbestos disease. 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