Pleural plaques and exposure to mineral fibres in a male urban

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456                                                                            Occupational and Environmental Medicine 1994;51:456-460

                            Pleural plaques and exposure to mineral fibres in
                            a male urban necropsy population
                            A Karjalainen, P J Karhunen, K Lalu, A Penttila, E Vanhala, P Kyyr6nen, A Tossavainen

                            Abstract                                              plaques according to the degree of exposure,
                            Objectives-The study aimed to evaluate                or estimated the aetiologic fraction of asbestos
                            the risk of pleural plaques according to              exposure as a cause of pleural plaques.' The
                            the degree of past exposure to asbestos,              aim of our study was to analyse these issues in
                            type of amphibole asbestos, and smoking,              a  series of 300 male urban necropsy cases.
                            as well as to estimate the aetiologic frac-           Exposure   to anthophyllite asbestos has been
                            tion of asbestos as a cause of plaques                common in Finland, and endemic pleural
                            among urban men.                                      plaques have been reported after environmen-
                            Methods-The occurrence and extent of                  tal exposure to anthophyllite.2A Therefore an
                            pleural plaques were recorded at necrop-              effort was also made to evaluate the role of
                            sies of 288 urban men aged 33 to 69 years.            anthophyllite as a cause of pleural plaques in
                            The pulmonary concentration of asbestos               the Finnish population.
                            and other mineral fibres was analysed
                            with scanning electron microscopy. The
                            probability of past exposure was esti-                Material and methods
                            mated from the last occupation.                       STUDY POPULATION
                            Results-Pleural plaques were detected                The study comprised all sudden, unexpected
                            in 58% of the cases and their frequency              deaths of men aged 35 to 69 years who had
                            increased with age, probability of past              died in Helsinki, and who had been examined
                            occupational exposure to asbestos, pul-              at necropsy between 15 January 1991 and 30
                            monary concentration of asbestos fibres,             January 1992 at the Department of Forensic
                            and smoking. The risk of both moderate               Medicine, University of Helsinki. The cases
                            and widespread plaques was raised                    where the body was combusted or macerated
                            among asbestos exposed cases, and the                were excluded. Inadvertedly two cases aged
                            risk estimates were higher for widespread            33 years were included. The necropsy series
                            plaques than for moderate plaques. The               (n = 300) comprises 30% of all male deaths in
                            age adjusted risk was higher for high con-           this age group in the area. One relative of each
                            centrations of crocidolitelamosite fibres            deceased person was interviewed personally
                            than for anthophyllite fibres. The aetio-            with a standardized questionnaire including
                            logic fraction of pulmonary concentra-               questions on smoking habits. The interview
                            tion of asbestos fibres exceeding 01                 was conducted in 167 cases.
                            million fibreslg was 43% for widespread                 Table 1 gives the distribution of causes of
                            plaques and 24% for all plaques. The                 death among the study population. About
                            median pulmonary concentrations of                   60% of the deaths were due to a disease, and
Institute of                asbestos fibres were about threefold                 80% of these were cardiovascular diseases.
Occupational Health,        greater among cases with widespread                  There were no deaths due to mesothelioma or
Helsinki, Finland           plaques than among those without                     asbestosis. Three cases of lung cancer
A Karialainen               plaques. No increased risk of pleural
E Vanhala                                                                        occurred. These were not suspected to be
P Kyyronen                  plaques was associated with raised total             asbestos related; nor was asbestosis evidenced
A Tossavainen               concentrations of non-asbestos fibres.               at their necropsy.
Department of               Conclusion-The occurrence of pleural
Forensic Medicine,          plaques correlated closely with past expo-           DETERMINATION OF PLEURAL PLAQUES
University of Helsinki,     sure to asbestos. The risk was dependent
Finland                                                                          The site and size of pleural plaques was deter-
P J Karhunen                on the intensity of exposure. Due to                 mined in 288 cases of the series. All shining
K Lalu                      methodological difficulties in detecting             white thickenings of the parietal pleura with
A Penttila
                            past exposures to chrysotile and such low            well defined borders were defined as plaques.
Department of Public        exposures that may still pose a risk of
Health, University of                                                            The detection of plaques was based on their
Tampere and                 plaques, the aetiologic fractions calcu-             macroscopical appearance only; no histo-
Department of               lated in the study probably underesti-               logical verification was used. The dimensions
Clinical Pathology and      mate the role of asbestos.                           of plaques in the right and left hemithorax and
Forensic Medicine,
University of Kuopio                                                             the diaphragm were recorded. The maximum
P J Karhunen                (Occup Environ Med 1994;51:456-460)                  total area of plaques was about 600 cm2. The
Correspondence to:                                                               cases were classified into three groups accord-
Dr Antti Karialainen,
Institute of Occupational                                                        ing to the total surface area of the plaques:
Health, Topeiuksenkatu      A relation between exposure to asbestos and          (1) no plaques: cases where no plaques
41 a A, FIN-00250
Helsinki, Finland.          the occurrence of pleural plaques has been           could be detected at necropsy; (2) moderate
Accepted for publication    shown in numerous studies. Only a few stud-          plaques: cases with bilateral plaques with a
5 April 1994                ies, however, have evaluated the risk of pleural     total area less than 100 cm2 and all cases with
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Pleural plaques and exposure to mineral fibres in a male urban necropsy population                                                                                                      457

                               Table 1 Causes of death among 300 Finnish male                      With this procedure an analytical sensitivity
                               necropsy cases                                                      (one fibre per sample) of about 0 07 million
                                                                       Age (y)                     fibres per g (f/g) dry tissue was reached. If
                               Cause of death              No          Range        Mean           only 1 to 3 fibres per sample were detected, a
                                                                                                   numerical concentration was still calculated
                               Disease                     179         36-69        54-8
                               Suicide                      52         33-69        48-7           and used in the analyses.
                               Accidental*                  41         35-65        48-3              An energy dispersive x ray microanalyser
                               Alcohol intoxication         21         36-62        47-7
                               Not definedt                  7         37-69        46-6           (Tracor TN 5500) was used to determine the
                               All                         300         33-69        52-2           fibre type. The intensity ratios of Si, Mg, Fe,
                               * Includes 18 cases of accidental intoxication, 14 cases of acci-   Ca, and Na were used in identification by
                               dental falling, three homocides, two cases of accidental suffo-     comparing peak ratios to standard spectra.
                               cation, two traffic accident, one case of accidental explosion,     Amosite and crocidolite have almost similar x
                               and one case of hypothermia. tCould not be determined
                               whether the death was due to an accident or a suicide.              ray spectra and are distinguished poorly. They
                                                                                                   are therefore not presented separately.
                                                                                                   Chrysotile fibres are poorly detected with
                               unilateral plaques only; (3) widespread                             scanning electron microscopy and conse-
                               plaques: cases with bilateral plaques with a                        quently a low concentration of chrysotile
                               total area of at least 100 cm2.                                     fibres was detected in one sample only. Low
                                  The necropsies and the determination of                          concentrations of tremolite fibres were
                               the plaques were carried out by three patholo-                      detected in six samples. Chrysotile and
                               gists (94 to 98 necropsies each). No signifi-                       tremolite fibres are included in the number of
                               cant differences in the determination of                            total asbestos fibres, but are not reported
                               plaques between the pathologists were found                         separately.
                               when this was applied as a variable in the sta-
                               tistical model (adjusted for age and asbestos                       STATISTICAL ANALYSES
                               exposure of the necropsy cases).                                    The statistical analyses were performed with
                                                                                                   the multinomial logistic regression model.
                               OCCUPATIONAL HISTORY                                                The confidence intervals (95% CIs) of the
                               The last occupation of the cases was derived                        variables are based on their standard errors.
                               from the necropsy records, and was used to                          The common odds ratios (ORs) for risk vari-
                               classify the cases into four exposure categories                    ables were also calculated with a cumulative
                               according to the probability of exposure to                         odds model of the ordinal logistic regression.
                               asbestos as follows (codes of the Nordic                            The conclusions drawn from the results of
                               Classification of Occupations5 in parenthe-                         these two models were similar. For the sake of
                               ses):                                                               clarity, only the results of the multinomial
                                                                                                   logistic regression are presented. The aetio-
                               Probable exposure                                                   logic fractions were calculated with the fitted
                               Construction occupations (codes 621-629,                            frequencies from the multinomial logistic
                               755, 761).                                                          regression.
                               Possible exposure
                               All other industrial occupations (codes                             Results
                               000-007, 501-619, 631-754, 756-759,                                 Pleural plaques were detected in 58% of the
                               762-902, 940-949).                                                  cases. The frequency of plaques increased
                                                                                                   with age, probability of occupational exposure
                               Unlikely exposure                                                   to asbestos, and the concentration of asbestos
                               Office type occupations, health care occupa-                        fibres in lung tissue, but not with the total
                               tions, and agricultural work (codes 008-499,                        concentration of inorganic fibres other than
                               903-939, 951-999).                                                  asbestos (figure and table 2). More than 80%
                                                                                                      1100 _
                               Unknown exposure                                                                 F88                  50                           31              22

                               Cases without any information on occupation;                            80
                               most of them with only a notification                                                                                                              32

                               "retired" in the necropsy record.                                                                                                                        ....2
                                ELECTRON MICROSCOPY                                                                                   31
                               A lung tissue sample from the peripheral left                           40                           : .. :

                               upper lobe was stored in 4% formaldehyde                                                        ,.                .........
                               and used for electron microscopic fibre analy-

                               sis. A low temperature ashing technique was                                             .-

                               used to remove organic tissue. Fibres were                                       __ 3
                               detected with a JEOL 100 CX-ASID4D elec-                                            c40          40-49                        50-59                >bU
                               tron microscope in scanning mode with a                                           (n - 34)      (n = 90)                      (n   =    87)   (n   =    77)
                               magnification of x 5000.6 All inorganic parti-                                                                      Age (y)
                               cles having a length to width ratio greater than
                               3 and roughly parallel sides were defined as                                            =E No plaques              X
                               fibres and counted. Fibres longer than 1 um                                                  = Moderate plaques
                               could be detected. A minimum of 200 viewing                                           Im Widespread plaques
                               fields was evaluated to find at least 4 to 30                       Occurrence of pleural plaques by age in 288 Finnish male
                               fibres per sample, depending on the density.                        urban necropsy cases.
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458                                                                                           Karijalainen, Karhunen, Lalu, Penttilda, Vanhala, Kyyronen, Tossavainen
Table 2 Age adjusted ORs ofplural plaques according to exposure to mineralfibres and                           smoking (smokers and ex-smokers combined)
smoking among 288 Finnish male necropsy cases                                                                  on pleural plaques was highly significant
                                   Extent ofpleural plaques                                                    (X2   =   19-1,   p < 0001).
                                   No plaques Moderate plaques               Widespread plaques                   Significantly raised ORs were found for
Exposure                           No            No    OR (95 % CI)          No OR (95 % CI)
                                                                                                               pulmonary concentrations of crocidolite/
                                                                                                               amosite fibres and plaques, whereas the ORs
Occupational groupt:                                                                                           of anthophyllite were not significantly
   Unlikely exposure               45            17    1 0 reference         17         1 0 reference
                                                                                                               increased when adjusted for age (table 3).
  Possible exposure                46            38    2-7 (1-3-5-7)*        42         2-4 (1-3-6-3)**
   Probable exposure
  Unknown exposure
                                                       2-7 (1-1-6-6)*
                                                       1.5 (0-5-4-9)
                                                                             26         3-4 (16-9 9)**         Interestingly, when no adjustment for age was
                                                                              3         0.4 (0-1-1.9)
Pulmonary concentration of                                                                                     used, a significantly increased risk of plaques
asbestos fibres (million 'g)t:                                                                                 was   associated with increased concentrations
   < 0.1                           45            17    1 reference           10          1 0 reference         of anthophyllite. Adjustment for age thus
   0 1 to 099                      66            49    1-6 (08-32)           52          2-7 (1-2-6-2)*
   > 10                             9            14    2-8 (10-8 2)0         26          8-1 (2-7-24)***       increased the risk estimates of crocidolite/
Pulmonary concentration of                                                                                     amosite concentrations and decreased the risk
inorganic fibres other than                                                                                    estimates of anthophyllite fibres.
asbestos (million f/g):§
   < 0-1                           46            24    1 0 reference         34         1 0 reference             The risk estimates shown in table 2 give an
      0l1                          74            56    1 1 (0-6-2-1)         54         0 7 (0-4-1-4)
Smoking:11                                                                                                     aetiologic fraction of 24% of all pleural
                                   14            10    10 reference           4          1 0 reference         plaques and 43% of the widespread plaques
                                   43            19    0-8 (0-3-2-1)         40          5-6 (1-5-21)**        for pulmonary concentrations of asbestos
  Ex-smoker                         8            13    2-5 (0-7-8-6)         10          5-3 (1 1-26)*
                                                                                                               fibres of > 0-1 million f/g. When the last
° p < 0 1; *p < 0 05; **p <0 01; ***p <0 001. tAdjusted for age. JAdjusted for age and
pulmonary concentration of inorganic fibres other than asbestos. SAdjusted for age and                         occupation (probable or possible exposure to
pulmonary concentration of asbestos fibres. IlAdjusted for age and pulmonary concentration of                  asbestos) was used as an indicator of expo-
asbestos fibres. Smoking habits known for 161 cases.
                                                                                                               sure, the corresponding figures were 26%
                                                                                                               and 29% respectively. Similar calculations
Table 3 Age adjusted and unadjusted ORs ofpleural plaques according to pulmonary                               resulted in an aetiological fraction of 12% for
concentration of anthophyllite and crocidolitelamosite fibres among 288 Finnish male                           both anthophyllite and crocidolite/amosite
necropsy cases
                         No plaques Moderate plaques                    Widespread plaques                        The median of the asbestos fibre concen-
Pulmonaryfibre                              OR         OR                      OR         OR                   trations and the proportion of cases with > 1
concentration                              unadjusted adjusted                 unadjusted adjusted             million f/g were two to four times higher
(million fig)            No          No    for age    for age          No      for age    for age
                                                                                                               among cases with widespread plaques than
Anthophyllite:t                                                                                                among those without plaques (table 4).
  <01                    60          19     10           1-0           17      1-0               1-0
  0-1 to 0-49            45          40    2-7**         1-7           42      3-0**             1-5           Similar results were found both when all cases
  > 0-5                  15          21    3-8**         2-20          29      4-5***            1-8           were analysed and when only cases with
  < 0-1                  88          49    1-0           1-0           38         1-0           1-0            probable exposure history were used in the
  0-1 to 0-49            27          21    1-1           1-5           28         1-90          2-8**          analyses. The concentrations were not
     0-5                  5          10    2-70          2-9           22      7-4***           7-7***
                                                                                                               adjusted for age. The cases with widespread
-p < 0-1; * p < 0-05; **p < 0-01; ***p< 0-001. tAdjusted for pulmonary concentration of                        plaques were on the average about 8 years
crocidolite/amosite fibres. tAdjusted for pulmonary concentration of anthophyllite fibres.
                                                                                                               older than the cases with no plaques.
                                  of cases with > 1 million asbestos f/g in lung
                                  tissue had plaques. Plaques were also                                        Discussion
                                  detected, however, in 43% of the cases with                                  The association between pleural plaques and
                                  unlikely exposure to asbestos according to                                   previous occupational exposure to asbestos
                                  their occupation, and in 38% of those with                                   was confirmed in this study. The risk
                                  < 0 1 million asbestos f/g in lung tissue.                                   estimates were higher for pulmonary concen-
                                     The risk estimates of both moderate and                                   trations of > 1 million f/g than for concentra-
                                  widespread plaques were raised among                                         tions of 0-1 to 1 million f/g, indicating a dose
                                  asbestos exposed cases (table 2). The highest                                response relation. In both of these categories
                                  risk was associated with widespread plaques                                  the risk of widespread plaques was higher
                                  and pulmonary concentration of asbestos                                      than the risk of moderate plaques. As we
                                  exceeding 1 million f/g (OR = 8 1). No risk                                  could adjust for age only, and not directly for
                                  of plaques was associated with increased                                     the effect of latency, it is difficult to intrepret
                                  pulmonary concentrations of inorganic fibres                                 the dependence of the size of plaques on the
                                  other than asbestos. Increased risks of wide-                                degree of exposure. A similar relation was
                                  spread plaques were found among smokers                                      found in a previous Italian study.7
                                  and ex-smokers (table 2). The overall effect of                                 Despite the strong association between
                                  Table 4 Pulmonary concentration of asbestos fibres according to the degree of pleural plaques among 288 Finnish male
                                  necropsy cases
                                                                                        Concentration of asbestos fibres in lung tissue (million fig)
                                                                                                                                                         Mean age
                                  Degree of pleural plaques                             No          Range         Median        Mean          >1 0 (O/o) (y)
                                  All cases:
                                     No plaques                                                         120          0-2-9       0-16   0-32    8          48 0
                                     Moderate plaques                                                    80          0-4-7       0 40   0 59   21          53.5
                                    Widespread plaques                                                   88          0-160       0 57    3-7   30          56-6
                                  Cases with probable exposure to asbestos according to
                                  the last occupation (group 1):
                                    No plaques                                                            20         0-1 8       0 37   0-57   20          48-1
                                    Moderate plaques                                                      17         0-2 5       0-66   0-83   29          50 5
                                    Widespread plaques                                                    26         0-160       0-92   8-4    46          56-4
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Pleural plaques and exposure to mineralfibres in a male urban necropsy population                                                           459

                               exposure to asbestos and the occurence of            exposed to crocidolite or amosite.'2 The
                               plaques, a significant number of all plaques         strong effect of age on the risk estimates of
                               (14% of the widespread and 24% of the mod-           anthophyllite is difficult to explain. It is pos-
                               erate plaques) were detected in cases with less      sible that the pulmonary fibre concentrations
                               than 01 million fig. As a significantly raised       may not be equally representative indicators
                               risk of plaques was associated with pulmonary        of past cumulative exposure to anthophyllite
                               asbestos concentrations from 0-1 to 1-0 mil-         and crocidolite/amosite fibres, due to possible
                               lion fig, some risk is also likely to be associ-     differences in the pulmonary clearance rates
                               ated with concentrations below 0.1 million           between these fibre types with significantly
                               fig, which were not quantifiable with our            different average dimensions. Differences in
                               method. The aetiologic fractions calculated in       latency may also have confounded the results,
                               this study are thus underestimations of the          as crocidolite was used in Finland mainly in
                               fraction of plaques attributable to asbestos in      1955-75 and anthophyllite in 1918-75.9
                               the study population. Actually the criteria             Pleural plaques have been described among
                               used for asbestos exposure (last occupation or       workers exposed not only to asbestos, but also
                               asbestos fibre concentration above 0 1 million       to erionite, attapulgite, wollastonite, and
                               fig) refer mainly to occupational exposure to        talc.'3 14 We did not find any increased risk of
                               asbestos, neglecting the role of environmental       plaques associated with increased pulmonary
                               and domestic exposures. Also the use of the          concentrations of non-asbestos fibres. The
                               last occupation as an exposure indicator prob-       other inorgance fibres detected were mainly
                               ably resulted in misclassification, as there is a    miscellaneous silicates conforming to the cri-
                               long latency time between the onset of expo-         teria of a fibre; also mullite and rutile were
                               sure and the occurrence of plaques.                  often detected. We do not know whether the
                                   Chrysotile is cleared more rapidly from the      concentrations of these fibres represent recent
                               lungs than the amphiboles, and even if trans-        or cumulative old exposures. Due to the small
                               mission electron microscopy is used, the             number of samples with an increased concen-
                               chrysotile content of lung tissue is not an          tration of a specific non-asbestos fibre we
                               equally representative measure of past cumu-         could not analyse these fibres separately and
                               lative chrysotile exposures as is the amphibole      thus discount the possibility that some of
                               content for amphibole exposures.8 As about           them may cause plaques. The relation
                               40% of all asbestos used in Finland during           between plaques and the non-fibrous inor-
                                1918-88 consisted of amphiboles9 and a              ganic particles was not studied.
                               mixed exposure to chrysotile and amphiboles              Our results support previous findings of an
                               took place in most of the industrial applica-        increased risk of plaques among smokers.'5-'8
                               tions, the amphibole content in the lung tissue      This finding may, however, have been con-
                               is a reasonably representative indicator of past     founded by different latency times between
                               exposure to asbestos. Yet some underestima-          smokers, ex-smokers, and non-smokers. In a
                               tion of the aetiologic fraction of asbestos may      study including adjustment for latency time of
                               have been caused by the poor detection of            asbestos exposure, no risk of plaques was
                               chrysotile. It must also be underlined that dif-     associated with smoking.'9 In the present
                               ferences in sampling, tissue digestion, and          material there was no correlation between the
                               methods of microscopy make between labora-           pulmonary fibre concentration and smoking.'2
                               tory comparison of pulmonary fibre concen-           The risk estimates of smoking were also
                               tration results difficult.8                          adjusted for pulmonary asbestos concentra-
                                   A high prevalence of pleural plaques has         tion (table 2) suggesting that the possible
                               been reported in Finland, Bulgaria, and Japan        effect of smoking on plaques is not mediated
                                in areas where the bedrock and ground               through an alteration of fibre retention.
                                contain anthophyllite.2-4A0II Endemic plaques           As the occurrence of plaques correlates
                                have also been reported in populations with          closely with past exposure to asbestos, it is
                                environmental exposure to other types of             obvious that within a given population, those
                                asbestos.' Even a low level of exposure to           with plaques should be more exposed on aver-
                                asbestos seems to be capable of causing an           age than those without plaques. This would
                                appreciable number of plaques when most of           imply that they are at a higher risk of lung
                                the population has been exposed. The influ-          cancer and mesothelioma. The 2-5-fold to 4-
                                ence of latency is important as most of the          fold differences in the median of pulmonary
                                exposures in areas of endemic plaques begin          fibre concentrations between those with wide-
                                in childhood. We found plaques in 58% of the         spread plaques and those without plaques are
                                male urban necropsy cases. Plaques were pre-         small compared with the entire spectrum of
                                viously reported in 52% of the necropsies of         pulmonary fibre concentrations, ranging from
                                Finnish urban dwellers and 32% of those living       < 0 1 million fig among unexposed subjects to
                                in the countryside.4 These figures are among         100-1000 million fig among heavily exposed
                                the highest that have been reported in random        patients with asbestosis or mesothelioma.20
                                necropsy series.' The results of the present         The epidemiological data on the value of
                                study do not indicate that anthophyllite fibres      pleural plaques as indicators of cancer risk
                                would be more potent than crocidolite/              remain controversial.2'-23
                                amosite fibres to cause plaques. A significant
                                portion of plaques in the Finnish population        We thank Ms Tarja Ruotsalainen for her aid in the office rou-
                                would still be attributable to anthophyllite, as    tines of the study, and T Kaustia, MA, who did the linguistic
                                                                                    revision of the manuscript. This work was supported by the
                                the number of persons exposed to anthophyl-         Finnish Work Environment Fund, the Finnish Foundation for
                                lite is higher than the number of those             Cancer Research, and the Yrjo Jansson Foundation.
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460                                                         Karialainen, Karhunen, Lalu, Penttila, Vanhala, Kyyronen, Tossavainen

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                                  Pleural plaques and exposure to mineral
                                  fibres in a male urban necropsy population.
                                  A Karjalainen, P J Karhunen, K Lalu, et al.

                                  Occup Environ Med 1994 51: 456-460
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