380 Annals New York Academy of Sciences

Transcription

1 11. A PRELIMINARY STUDY OF OBSERVER VARIATION IN THE CLASSIFICATION OF RADIOGRAPHS OF ASBESTOS- EXPOSED WORKERS AND THE RELATION OF PATHOLOGY AND X-RAY APPEARANCES A. Caplan," J. C. Gilson,t K. F. W. Hinson,$ J. C. McVittie," J. C. Wagner+ Ministry of Pensions and National Insiwance, London, England" Medical Research Council, Pneumoconiosis RPsearch Unit, Llandougli Hospital, Penarth, Glamorgan, Walest Department of Pathology, The Brompton Hospital, London, England$ The Conference on the Biological Effects of Asbestos has provided an opportunity for a preliminary study of the inter- and intra-observer variation using the extended I.L.O. Classification suggested by C. P. Theron, and also for investigating the relation of an agreed classification of a series of radiographs with the macroscopic and histological features of the lungs at autopsy. Material To make this study the following material was collected: 1. Fifty chest radiographs of cases of asbestosis diagnosed in recent years at the South African Pneumoconiosis Bureau in Johannesburg. 2. Sixty-four chest radiographs of cases of asbestosis diagnosed at the London Pneumoconiosis Panel of the Ministry of Pensions and National Insurance. 3. Reports of the macroscopic and histological appearances of the autopsy of 54 cases in the London area. The material was selected to include recent cases applying for compensation at the two centers with complete or nearly complete records. In three-quarters of the cases the interval between the chest films and autopsy was two years or less. Female cases were excluded, as were cases of asbestosis complicated by tuberculosis, and cases of mixed pneumoconioses or other forms of pulmonary fibrosis. In the United Kingdom series the incidence of lung cancer was so high (see Ruchanan, 1965) that exclusion of these cases was impracticable. Plan of Investigation A preliminary exchange of a small group of films was made between South African and United Kingdom readers to reveal any gross discrepancies or ambiguities in the proposed classification. The main group of South African and United Kingdom films was then exchanged, and an agreed reading recorded by C. P. Theron and G. K. Sluis-Cremer together in South Africa, and McVittie, Caplan, and Gilson in London. The whole group of films (114) was then reread in New 379

2 380 Annals New York Academy of Sciences York before the Conference by Theron, Sluis-Cremer, McVittie, and Gilson working together. In addition, some separate studies of repeat reading by some of the observers were made. In 54 of the 64 United Kingdom cases the records were sufficiently complete for a comparison to be made between the agreed reading of the radiographs by the three United Kingdom observers and the macroscopic and microscopic assessment of the pathologists. Results (a) Radiographic Appeara.nces. TABLE 1 shows for the two groups of readers separately and for the final agreed reading the number of positive reports under the five main headings of the Classification. Linear markings were recorded more frequently by the South African readers but in 70 of the 114 films there was agreement between South African and United Kingdom readers before the final meeting. At this meeting nearly two-thirds (57 per cent) of the films were agreed to show this type of abnormality. Large opacities, as defined in the I.L.O Classification, were present in 14 per cent of the films. This is of interest because it has often been assumed that such radiographic appearances (whatever the underlying pathology) do not occur in asbestosis. In addition, 20 per cent of the films were agreed to show small opacities (simple pneumoconiosis) and the agreement between the two groups of readers before they met was reasonably good. The reading of pleural thickening (separately for diaphragm, wall, mediastinum, and fissure, but here grouped together) is part of the extension of the I.L.O Classification suggested for recording the appearances of asbestos-exposed workers. TABLE 1 shows that the prevalence reported by the two groups of readers separately was very close and the final agreement, though rather less, was still over 60 per cent. Pleural calcification which includes calcified plaques (but not localized areas of pleural thickening which do not show clearly defined areas of high opacity) did not show quite such good agreement between the readers before meeting, but at the final reading the prevalence of these changes was similar to that of the large opacities. TABLE 2 shows evidence of intraobserver agreement for three observers -two in South Africa and one in the United Kingdom -when rereading 20 of the group of 114 films. In general the intraobserver agreement, using the extended classification, was fairly high in this group of films when division was limited to the five main subgroups of the classification. But the table shows that a single observer s recordings may deviate appreciably from the final agreed reading. For example, for pleural thickening (all sites), observer two reported its presence in only 13 of the 20 films, whereas

3 Caplan et al. : Preliminary Study 38 1 TABLE 1 EXTENDED I.L.0. CLASSIFICATION OF RADIOLOGICAL APPEARANCES IN ASBESTOS-EXPOSED WORKERS. OBSERVER AGREEMENT BETWEEN SOUTH AFRICAN AND UNITED KINGDOM READERS ON 114 RADIOGRAFHS I Linear: All sites and types United Kingdom readers 77 South African readers 88 United Kingdom and Agreements Percentage South Africa final agreed reading Large opacities: A, B, and C Small opacitie$: 1,2,3, p,m,n Pleural thickening: All sites Calcification: All sites observer three reported it present in all 20 films. These studies were made before the final meeting in New York at which it was possible to remove some of the ambiguities, and these will be discussed in greater detail elsewhere. (b) Pathologg/Radiologg Correlation. This was based on 54 United Kingdom cases in which the records were sufficiently complete. Both lungs were usually available and they had been fixed in formalin but not always inflated. Also in some cases the autopsy was made elsewhere, and so the parietal pleura was not always available for examination. Macroscopic Appearances During macroscopic examination the condition of the pleura was recorded and an assessment of the severity of fibrosis of the lung made. Thickening of the visceral and parietal pleura is a common finding in cases of asbestosis. The degree of pleural thickening is not necessarily correlated with the severity of asbestosis in the underlying lung. This may vary from slight opaqueness to complete symphysis and thickening of both pleural layers to form a cartilagenous-like covering up to two em. in thickness over the entire lung surface. In other cases discrete pleural plaques

4 382 Annals New York Academy of Sciences TABLE 2 EXTENDED I.L.0. CLASSIFICATION. INTRA- AND INTER-OBSERVER AGREEMENT ON 20 FILMS BY 3 OBSERVERS FROM SOUTH AFRICA AND THE UNITED KINGDOM Number agreements first and second reading Observer Final agreed reading Linear markings Large opacities Small opacities Pleural thickening Calcification l8 16 l : 20 $ I/ 20 i 19 O j 19 I I 1 1; 1 1: l may be present on an otherwise normal pleura; these are usually multiple and may contain areas of calcification. A common site for single plaques is the diaphragmatic surface. Severity of Fibrosis The degree of asbestosis was graded using the following criteria : 1. Slight asbestosis. In the earlier cases the presence of fibrosis is only noticeable to the touch, and the tissue feels more firm and resilient than normal. In more developed cases the subpleural intralobular septa become prominent. 2. Moderate. The induration of the lung is more definite and the lung tissue feels firm. There is a sharp edge formed between the cut surface and the pleura. The periphery of the lung appears bloodless. The intralobular septa are prominent throughout the lung and those in the subpleural area are definitely thickened. 3. Marked. The lung feels rubbery and is markedly indurated. The in-

5 Caplan et al. : Preliminary Study 383 tralobular septa are thickened and fibrosed. In some subpleural areas there are foci of fibrous tissue extending from the septa into the lung parenchyma. In the earlier severe cases these foci of fibrosis are discrete but as the disease progresses the size and number of these fibrous foci increase. Finally large fibrous areas develop ; these are usually subpleural. Asbestos Bodies Wet smears from fluid expressed from the cut surfaces of the lungs were examined immediately for asbestos bodies. This sample procedure gives confirmation of exposure within a few minutes; the bodies can be found up to 30 years after the last exposure and it is most unusual to find fibrosis due to asbestos and not to be able to find bodies by this method. Microscopic Appearances Blocks were taken for histology from those parts of the lung which were most severely fibrotic to the naked eye. The sections were stained routinely by H. and E. and van Gieson. In the United Kingdom the most severe disease is found in the subpleural zone of the posterior parts of the lower lobes or, if the upper zones are affected, the lingula and middle lobes will be most markedly affected. In about half the cases a tumor was present at autopsy and the interpretation of sections from these cases was often difficult. The problem was to distinguish between the fibrosis due solely to asbestos and that associated with collapse and infection following bronchial obstruction. Difficulties in interpretation were also experienced in those cases which were exposed at some time to other toxic dusts as well as asbestos; fibrosis following radiotherapy was a further problem in one case. On the basis of the histological appearances the disease was again assessed as slight, moderate, or marked: (1) Slight. In the early cases of asbestosis the lesions are confined to the respiratory bronchioles of scattered acini. The walls of these bronchioles are thickened, this being partly due to an increase of reticulin fibers in the walls, and partly due to proliferation of the reticulin fibers among the dust-containing phagocytes which accumulate in the alveoli arising directly from these bronchioles. Occasional asbestos bodies and fragments of fibers can be seen in the bronchiolar walls. Numerous fibers and bodies are present in the lumina, some within the phagocytes, while many are lying free. More acini become involved as the disease advances, and the fibrosis extends to involve the alveolar ducts and atria of the respiratory bronchioles, as well as the walls of adjoining air spaces. A few lesions may extend to involve entire acini with thickening of the intralobular septa. The asbestos bodies and fibers in the interstitial tissues have become more numerous. (2) Moderate. Sections from moderate cases of asbestosis show an in-

6 384 Annals New York Academy of Sciences crease and condensation of the peribronchiolar fibrous tissue in which the reticulin has been partly replaced by collagen. The fibrous tissue at this stage surrounds the bronchiolar vessels. The lesions are now widespread throughout the sections and there is an early generalized interstitial fibrosis with definite thickening of the septa. The thickened peripheral septa are continuous with the visceral pleura in which similar changes are frequently seen. In some cases there is a cuboidal metaplasia of the epithelium lining the alveoli, arising from the respiratory bronchioles and alveolar ducts. Although there is a diffuse interstitial fibrosis, the walls of the terminal air sacs are seldom involved at this stage. (3) Marked. In marked cases large fibrotic lesions are seen, in which distorted bronchioles appear as narrow clefts surrounded by occasional surviving alveoli. These are lined by cuboidal epithelium while the walls of the distal air spaces are thickened and frequently contain numerous asbestos bodies and fibers. In some of the areas of fibrosis, numerous fragments of asbestos bodies, fibers, and other dusts are seen; in others there are only sparse fragments of bodies and fibers. Some of the massive fibrotic lesions contain areas of hyaline fibrosis closely resembling that seen in silicosis ; whorling is, however, uncommon. Similar lesions to these are mentioned by Gloyne (1938), but it is possible that this may be due to a combination of free silica and asbestos dust. The septa in these marked cases are gradually thickened and appear avascular. Relation between Pathologg and Radiographic Features These assessments of asbestosis and the presence or absence of pleural thickening or calcification of the pleura were used to relate the pathology and X-ray appearances. TABLE 3 shows this comparison. Pleural thickening was reported rather more frequently on the X-ray than at autopsy. But in three-quarters of the 45 cases in which it was noted on the X-ray, it was confirmed at autopsy; there are also seven cases in which it was detected at autopsy but not reported on the X-ray. Calcification of the pleura was infrequent in this group of cases. Of the seven cases detected on the X-ray, only three were confirmed at autopsy. This may well be in part due to the incompleteness of pathological records which were not, of course, made with this investigation in view. The linear markings (all sites) on the X-ray were related first to the macroscopic grading of asbestosis which, for this purpose, was divided into two groups: present (all grades) or absent. The table shows that of the 45 cases with linear markings on the radiograph, 37 (82 per cent) showed macroscopic evidence of asbestosis. There were, however, also eight cases which showed linear markings on the X-ray but no macroscopic evidence of asbestosis, and an equal number in which this condition was detected at autopsy but in which there was no linear marking recorded

7 Caplan et nl. : Preliminary Study 385 TABLE 3 X-RAY/PATHOLOGY CORRELATION IN 64 u NITED KINGDOM CASES Pathol: Per cent Pleural thickening X-ray 76 Calcification X-ray Linear /Pathology Macroscopic X-ray Linear /Pathology Microscopic X-ray + 87 on the X-ray. The table also shows a very similar pattern of the relation of linear markings to microscopic evidence of asbestosis. Comment This is a preliminary study of an extended I.L.O. Classification of the radiographs of asbestos-exposed workers, using the techniques for investigating the inter- and intraobserver observations which form part of the basis on which the 1950 and 1958 I.L.O. Classification was constructed. The results of this preliminary study are, in our view, sufficiently encouraging to warrant an extended investigation with a wider range of films spanning the full range of abnormality, and from a number of different countries and occupational groups (mining, textiles, insulating workers, etc.). This study has shown that it is possible to build on the 1958 I.L.O. Classification a system which promises to be useful for the classification of asbestosis. It is important to emphasize that many asbestos-exposed workers also inhale other types of dust and it would, therefore, seem logical to use a classification describing the results of exposure to a mixture of dusts if possible. In reading these X-ray films we have not been worried by the lack of a specific category of ground glass appearance. We think that some of the cases previously put into this group were due to poor technique; others probably showed diffuse pleural thickening which should be reported as such; while in other films the abnormality is principally one of an increase of linear markings.

8 386 Annals New York Academy of Sciences There is some evidence that there may be marked differences in the prevalence of, for example, linear markings, pleural thickening, or calcification, etc., in different groups of films from different occupations or racial groups. If this is so, information will be lost by attempting to grade asbestosis radiologically without taking into account the separate types of abnormality present. The separate recording of the qualitative differences of radiological appearances on a semiquantitative scale is the scientific principle on which the I.L.O. Classification is based and it appears possible to extend this to asbestos-exposed workers by : (1) Recording the presence of linear markings in zones 1, 2, and 3 of each lung separately. In our experience a separation of the linear markings into fine and coarse, although obvious in a few films, was too poorly reproducible within and between observers to be usable. (2) Pleural thickening is raised from an additional symbol (I.L.O. 1958) to one of a main category, and its site is recorded (diaphragm, wall, mediastinum, or fissure ). (3) Calcified pleural plaques appear sufficiently frequently in asbestosexposed workers to record these systematically and separately according to site (diaphragm, mediastinum, wall, and fissure). The suggested grading of asbestosis pathologically is similar to that reported by Wagner (1960 & 1962) and, if acceptable internationally, would help to increase comparability of epidemiological studies in different parts of the world. References BUCHANAN, W. D Asbestosis and primary intrathoracic neoplasms. This Annal. GLOYNE, S. R In Silicosis and Asbestosis. : 225. A. J. Lanza, Ed. Oxford University Press. London, England. WAGNER, J. C In Proceedings of the Pneumoconiosis Conference. : 380. A. J. Orenstein, Ed. Churchill. London, England. WAGNER, J. C The Pathology of Asbestosis in South Africa. Thesis presented for the degree of Doctor of Medicine in the department of Pathology of the University of the Witwatersrand, South Africa.