Inorganic fibers in lung tissue from patients with pleural plaques or malignant mesothelioma.

A. Inorganic fibers in lung tissue from patients with pleural plaques or malignant mesothelioma. Scand j work environ health 7 (1981) 109-113. The concentration of inorganic fibers in the lungs of patients with malignant mesothelioma and pleural plaques has been compared to that of patients without cancer or chronic respiratory diseases. The fiber concentrations have been determined by scanning electron microscopy and given as number of fibers per gram of dried tissue. A statistically significant difference in inorganic fiber content was found between the different groups.

vaIl!t factor. The content of linorganic fibers in ,the lungs of exposed workers has also been relaJted Ito the human pathological reaction (1,12).
In -this paper we have compared the asbestos concentration in lung tissue from patients with malignant mesothelioma of the pleura and from patien'ts with pleural plaques :to that of a Teference group comprising patients who died of coronary or cerebrovascular diseases.

Subjects
Lung tissue was analyzed from a total of 41 patients who were divided into three different groups. mortem diagnosis of malignant mesothelioma. It included the first 15 patients recorded in an epidemiologic study. There were two insulators and four asbestos cement workers in the group, all probaibly having had a high occupational exposure to asbestos. Information about occupational exposure was obtained from dif-rereIl!t sources, eg, personal interviews, industrial Physicians, and social insurance offices.
Pleural plaque group. Another group comprised 14 patients (numbers 16-29) with parietal pleural plaques of an individual size, recorded during autopsy, of at least 3 X 3 em. This was the only criterion used for Ithe selection of the lung tiiSSue in these 'Cases. Information about occupationa'l exposure was ndt available.
Reference group. The third group con-Sisted of 12 pa'1ii.ents (numbers 30-41) Who had died of coronary or cerebrovascular diseases. The lung tissue specimens were obtained du~ing consecutive hospital autopsies, with the exception that specimens from persons under 40a of age or with cancer or ohl'onic respiratory diseases were excluded. Information aboUlt occupational exposure was not available. 0355-3140/81/020109-5

Methods
The subjects were traced 1Jhrough close cooperation with val'ious pathological departments and from information from the Cancer Registry of Norway. Tissue was obtained as whole lung specimerus, pieces of lung, or paraffin-'embedded autopsy material.
The samples comprised a cut from the pleura and a few centimeters into the central part of 1Jhe lung. As intra-and interlobar filber concentration vaniations oc-cur (10), tissue was sampled from borth 1Jhe upper and lower l'obes.
Normally, tissue from the left lung was tak1en; however, in !the cases of complete tumor affection of ,the lung, as for many of the mesotheliomas, samples from the corresponding lobes of the right lung were analyzed. In the cases in which paraffinembedded material was 'analyzed, no information about tissue location was obtai-ned. For patients for whom several analyses were made, tihe highest oounts obtained have been given tn the tables. In some cases only tumor-infiltrated lung tissue was avail'able for the analysis, and the counts may have been low for these specim'ens.
Small tissue pieces were cut and dried. Ol"gank material was removed by low-temperature plasma ashing. The ash was analyZled ac-cordJing to the methods descl"i,bed by Gylseth et al (4,5). No effort was made to identify all fi.'bers as long as only fibers broader 1!han 0.1-0.2 Jim could be identified by our method. Table 1 presents relevant data on 1fue 15 paUents with malignant pleural mesothelioma. The gr<lUp included two insulation workers and four asbestos cement workers. The remaining nine, including two females, had had val'ious occupations. We have not been able to trace any oQCupational expOSUl'e for the houslew,ife wi,th 41 million fibel"s per gram of dried tissue, whiLe the other female had, in her youth, been employed in a company processing asbestos. The total group had a mean age of 65 a at death. The time from first exposure until death varied from 19-59 a, excluding cases 3, 6 and 8, for whircih no exposure dat:a were obtained.

Results
In table 2 the corresponding information is given for the 14 persons with pleural plaques. In this group, Which had a mean age of 65 a at de~th, exact information about exposure was not obtained.
The results for the reference group, which comprised 12 persons, are given in

Dls,cussion
The dose required for the initiation of malignant mesothelioma is small and may even be acquired in nonoccupational exposure to asbestos (3,7,8). It has been stated Ithat the mesothelioma rate in-Cl'eases as intensity, duration of exposure, and time from first asbestos exposure increases (1). Whitwell et a1 {l2) have suggested 1Jhat a defin1te relationship exists  between the number of fibers and the presence of mesQtheliomas. Scanning electron microscopy (SEM) is traditionally not used for the analyslis of f~bers in lung iUs-sue. However, if we compare our l'esul'ts to data from similar studies obtained either by optical microscopy or by transmission electron micro-scopY,the results are at 'least within the same order of magnitude (1,12). As stated m our prev,ious work (10), mainly amphihole fi:bers are found, iIIlcluding croci-doHte,amosite and anthophyllite. Chrysotile is, probably due to lack of sensitivity of the method, seldom found. Therefore, no effort has been made to identify the broadest 'fibers, all of them with a morphology cOl'l'esponding to the amphiboles.
All the patients in the mesO'1Jhelioma group had two million fiJbers or more per gram of dried tissue, whereas only one person in the referen<::.e group had that many fibers {a driv,er). According to our method of analysis (4,5), the persons who had not been occupationally exposed had normally less than one to two million fi:bers per gram of dried tissue. As expected, ,the insulation workers and the workers in the asbestos cement industry had the lhighest exposures. The occupation given for the other patients in this group may also 1ndicaie previous asbestos exposure, but to a less degree than for the insulation and asbestos cement workers.
There were two females in the mesOlthe-1ioma group, one wi1fu a considerable fiber concentration ,in her lungs (41 million ftbers per gram of dried tissue). No previous occupational asbestos exposure was found for the woman with the highest fiber content. However, occupa'tional exposures of Short duration are difficult to pinpoint and ,cannot be excluded in this 112 case. Household exposure cannot be ex-Cluded ei1fuer. The other female had, at an age of approx1maltely 20 a worked in a company importi!I1g asbestos from South Africa. The ,exposure was probably rather short. The results f.rom this woman sugg,est that a signiflcant number of fibers is retained in the lungs for a long 'time.
Evidence eX!ists of an associ'ation between pl€ural plaques and asbestos expo-sur€ (6). However, few reports have been published a'S to ,the fiber concentrations in the lungs of persons with pLeural plaques. Our data inrdioa'te a rather low and possibly intermittent exposure for most of the subjects with pleur<rl plaques, ie, if fiber oonc-entration reflects exposure. Thus pleur.al pl'aques may be associated wtth low asbestos exposure and low lung fiber concen'traJ"bions, if asbestos were the only causative agent in these cases. Many of the patients in the pleural plaque group died of a primary cancer, a,nd therefore the results may be biased. However, we have no ev.idence ,thus far of cancer patients wi,thout pleural plaques having a higher lung fiber concentration than tha,t of Ithe reference group.
According to the median lung fiber concentration, the mesothelioma group had eighteen times 'higJJ.er values than the refer-ence group, while the corresponding nUlmbers for the pleural plaque group were approximately four times thal1; of the reference group. The results demonstrate a significant difference in lung fi.,ber burden between the respeotive groups.