Document ym7goLD4a9jMvwQkbypjqnpME

tit'prntu'4 from the A. St. A. Atef\iv,'t >( truh>>trial Health Uputub.r /A\1 \A, !J, //>. J#if-28s Copyright /P.*.5. by Jnitric** Medical .Itweiotuiii Swd** m Csnfntn(al fatoewy Hrtfqqdtfcalayy G. W.H. SCHtfElS. M.O., 05c, Sore** LA*, MX The observation* flowing, respectively, from the intratracheal and the inhalation experiments described bv Schepers and Delahant * will be presented separately. Glass wool is fabricated by ejecting molten glass hy means oi supercharged steam into a chamber where fragments varying from 25 k> 50 cm. \r> length fall.* Sharing the process of manipulating this product in the manu facturing of textiles, fragments are released imo the air and have been known to act as skin irritants* but they have not been in criminated as a cause ot.pulmotiarv fibrosis,' though occasional cases have been cited in connection with which the inhalation of glasswool dust has been implicated as acontribut ing cause of pulmonary disease of variable se verity,* At the most, these reactions have Iwen attributed to mechanical irritation, as glass does not contain any free silica. Pow dered glass has been shown to be inert for subcutaneous or ocular tissues. The increasing exploitation of glass wool and of glass fibers in industry and the simi larity between glass spicules and asbestos fibers necessitate constant vigilance con cerning the properties of these glass fibers. The description of the pulmonary lesions resulting from the introduction of glass wool into guinea pjg lungs will serve to show* that, though the silicon element in the glass is present as a silicate and thus does not provoke the characteristic nodular disease associated with quartz inhalation, glass fibers of the caliber and length used in this study, hen effectively lodged within the lung tis sue, are nevertheless capable of producing quite remarkable lesions. IS'TBATRACHE.U. STUDY* CLASS WOOL One month after the intratracheal intro duction . of glass-wool fibers, areas of lung tissue are demonstrable in which the alveoli contain nwicrous rrraitinacleated giant ceils in which glass fibers may be found. Some alveoli may contain several such giant cells, and in others, the giant cells are so large as to fill the greater part of the alveoli. The smaller'the fibers introduced, the larger are the associated giant cells. Xo free-lying glass fibers could be observed. The alveolar walls are infiltrated by macrophage cells and occasional polymorphonuclear leucocytes at numerous points. There is. however, no appreciable hyperemia, and only isolated glass fibers have penetrated imo the alveolar walls, either separately or in a phagocytosed state. Many of the longer fibers appear also to have either extremity embedded in an adjacent alveolar wall (Fig. \A). At several sites these islands of phagocytic reaction involve the lung ly*nph nodes, which are considerably hypertrophied, with lym phocytes overflowing into proximal alveolar walls (Fig. 15). Glass fibers are not, how ever, found in the parenchymal lymph nodes. The hilar lymph nodes show some endotbelioid cell hyperplasia and prominent lymph follicles in which macrophages, with minute glass spicules, may be found. The lung fields intervening between these affected areas appear relatively normal, except for a measure of incipient atrophic emphysema. Recorded for publication July 11, 1955. Director. The Saranac Laboratory, Around some of the smaller bronchioles the cellular infiltration may be quite abundant. 01 501 1578 i VWMH181 1 Fig. 1.--Acute pulmonary tissue reaction to long-fiber glass woo!--guinea pigs; intratracheal injection oi 2Q*-:0 fibers: result aster one month. A, giam macrophage filler! with glass spicules, some of which are seen to penetrate the alveolar walls and Wood vessel walls. B, proliferation oi lymph nodes and extension oi the cellular reaction into adjacent alveolar walls. Cy peribronchiolar cellular inflammatory reaction, with epitheiuiiiatton ol adjacent alveoli. D, wide rone oi cellular infiltration around a bronchiole, which is distorted and linked to atrophic alveolar ducts: degenerative changes in adjacent vascular bundle. 01 501 1579 and the fining epithelium show* considerable hyperplasia. with sonic superficial desquama tion. Very occasionally, glass fibers may be seen adhering to the surfaces of the bron chial epithelium, hut there is no mucosal reaction to their presence, These affected bronchi and farmctuoles occur in. proximitv to the islands of parenchymal reaction ` Fig. IC>. At isolated sites there is a broad reactive cellular zone around the smaller bronchi, which completely obscures the pulmonary histioarchitectonics, The trapped bronchus may be distorted and distended (Fig. \0>. The tracheal epithelium tends to be some what hyperplastic and is covered by a thin layer of exudate which contains polymor phonuclear leucocytes. Two months after the introduction of the glass-wool dust, much of the reaction seen wntton the first month has receded. There now arc fewer parenchyma! islets in which glass-filled macrophages occur within the alveoli. More frequently, these macrophages are to be seen diffusely scattered throughout the lung tissue. Isolated foci of intense, and even confluent interstitial cellular infiltra tion ateo occur. A new feature is the abundant presence of eosinophile cells within the alveolar walls, the peribronchial or perivascular tissues, and also sometimes within alveoli or bronchiolar lumina. The bronchi and trachea show no material pathological deviations at this stage. The lymphatic reaction has become modi fied. and the lymphocytes now occupy peri vascular and pericapillary positions mainly. This change is fairly diffusely disseminated. The hilar lymph nodes show no further re action. At the end of )2 months, a considersole amount of glass still persists within the lung tissue, and there arc isolated islets of confluent cellular pneumonitis. More of these fibers are now to be found within the 'interstitial pulmonary tissue in areas where such proliferation persists and such fibers tend to be relatively long. Generally the short fibers are within macrophages with relatively atrophic alveoli, and the larger fibers are to be found in the alveolar walls. The bron chioles show some superficial epithelial des quamation < Fig. 2A). Occasional bronchioles may 1e trapped within hyperplastic areas and appear stenostd. These areas differ from those demon strated after the first month in that there are many more fibrocytes than inflammatory cells and the tissue has a poorer blood supply (Fig. 2B). In the lymph nodes, the glass is now* condensed into formless focal deposits, with no evidence of macrophages but with some cellular condensation around them (Fig, 2C). The lymph nodes of the lung parenchyma are normal once more. At the end of 18 months, the interstitial parenchymal reaction may yet persist but is now minimal in degree. Glass fibers are now but scantily represented and occur mostly in the alveolar macrophages. Some glass rods may, however, be displayed within the interstitial tissues, and some are still seen to transfix alveolar walk, The main abnor mality' now concerns the bronchi and bron chioles which tend to be regionally distended and display many crypts and papillae cov ered by a thin lining of cufeoidal or squamous cells. This bronchiectasis and bronchiolcetasia had already commenced at 12 months, but the crypt and papillary formations are later trends. The condition is more marked with exposure to the shorter, narrower fibers (Fig. 20). INHALATION EXPJ81S1ENT: ASt> LESS FIBESS The essential difference between the result of the introduction of glass wool by means of a single intratracheal injection and the slower inhalation of the fibrous particles under experimental conditions is quite strik ing. There is no acute response of the bronchial mucosa to the inhaled glass-wool spicules which impinge upon its surface (Fig. $A). Very little reaction occurs before the fourth month, whereas in the intratracheal experi ment the maximal effect is achieved within (he first month. By the fourth month there are many macrophages in the alveoli. 01 501 1580 4 t i Fig. 2--Chronic pulmonary reaction to Iong-fifc<r glass woot--.guinea pigs: intratracheal injection ot 20m-?0 fibers: result at 12 months. A, persistent dominantly cellular reaction around a distorted bronchiole', numerous glass fibers discernible. 8, diffuse peribronchial cellular reaction now; largely nbrocytK in character. C, amorphous accumulation within a lymph node, with a reactive surrounding aooe. D. distortion and incipient crypt formation in a bronchiole which is surrounded by a fibrotk process. 01 501 1581 . *75' r guinea {response to inhaled short-fiber glass wool-- qpig*; inhalation study Jess than 6 fibers. A, presence ot |u?.w| dost within a brcnehus on the I8eh day showinir absence of immediate reactton, <?. cellular infiltration of alveolar wall*, wh hyoernlasta ol pui2\fnar^ lymph nodes <reaction at four monthsI. C, epithelial hyperplasia and SCT^aTjfLpfilr^h^rrsfeaC* w' ?r'n?ul* .*?* progressive narrowing of the iur2 aiSTayea*) r hs)' D> ***&ion ot the alveoli adjacent io a bronchos freaction 01 501 1582 Ihoc arv >cpiirate crlU, ami there is very little ot a tendency to giam-dell formation. Hosmophiles are fairly numerous now, whereas they appeared later only m she intratracheal experiment. Glass fibers, on the contrary, are very scarce, and because cite inhaled substance contains fibers less than tv* only, they are limited to short -pieules. ail oi which are intracellular, In the luttg parenchyma, there are patches * almost solid cellular reaction around the lymph nodes whose proliferating cells over flow into adjacent alveolar walls, while the presence of large numbers ot macrophages within such alveoli contribute to the impres>ion of a diffuse pneumonitis < Fig. SB). There is no hyperemia. The hilar lymph nodes show no particular reaction. In the bronchi, there is considerable cpitiielial Hyperplasia and cellular desquama tion, and a tendency to papilloma formation is present in the smaller bronchioles, with mucosal hypertrophy in the larger air pas sages, There tends to be marked peribron chial cellular infiltration at this stage, with the evolution of multiple bronchial glandular cysts and mucosal papillae. A tendency toward bronchiectasta and bronehiolectasia has commenced {Fig. 3C). By the end of nine months, glass fibers commence to make their appearance in dus ters within alveoli as well as in the koniophores. The bronchtolar crypts are more prevalent, and there is fairly considerable peribronchial and perivascular cellular in filtration, with some collagen deposition. A year after the commencement ot the glass-wool inhalation experiment, the guinea pig lungs show a bronchitis and bronchiectasia, with marked focal cellular pneumonitis. The bronehial {bronchiolar) disease con sists of epithelial proliferation and distention of the lumina, with extension of the bronchioJar epithelium over the walls ot the proximal alveoli. This produces a very characteristic lesion, comprising a dilated bronchiole sur rounded by a rone of epitbeltaltzed alveoli (Fig. 3>). A fibroceilular reaction about these bronchi may enclose such epithelSaltzed alveoli, creating a spurious adenomatous effect (Fig. 4.f), A considerable degree of bronchial epithelial hyperplasia has super vened, and the lining shows marked rugosity and incipient metaplasia. There is no ulcera tion or submucosal infiltration Fig. 4B). The parenchymal islet* of reaction are composed of thickened alveolar walls, with multinucleated giant cells and macrophages occupying the majority of such alveoli and containing many glass fibers. Occasional co&inophile cells are to be seen, but there is no hyperemia or collagenosis (Fig. 4C). In the vicinity of lymph nodes, there is considerable dissemination of lymphocytes into adjacent alveolar walls. Many blood vessels also are ensheathed in fairly thick col lections of lymphocytes. Some such arteries show medial myohjpertrophy. The hilar lymph nodes are enlarged, owing mostly to medullary endothelial hyperplasia and in filtration by means of macrophages, many of which contain glass fibers. By the 18th month of glass-wool dusting, the pulmonary tissue pathology ceases to reveal any significantly new features. There still is intense alveolar wall thicken ing due to macrophage and plasma cell in vasion, and there is also almost universal minor capillary hyperemia, with conspicuous perivascular macrophage infiltration. In nu merous areas there is merely abundant incra* alveolar macrophage formation and no alveo lar wall reaction of anv consequence < Fie. 4D). The parenchymal lymphatic tissue still escapes, even when lymph nodes mav be almost completely surrounded by an exten sive accumulation of macrophages. The bron chitis persists and comprises mainly epithelial hyperplasia, with increased goblet-cell activ ity and cellular catarrh, and there is also con siderable peribronchial cellular infiltration. Glass fibers arc present everywhere, in stained sections they may be difficult to sec. but scattered giant cells are to be found within alveoli. Dark-field examination of un stained sections shows up the universal dis tribution of the glass to good advantage 01 501 1583 *r> ' Fig, 4--Chronic reaction so inhaled short.fiber glass wool--guinea pigs: inhalation stud'* oi less than 6m fibers. .4. peribronchial fibrocellular reaction which has surrounded epuheliafired alveoli, thus producing a spurious adenomatous appearance (reaction at one >ear). 5, hvperefasia ol bronchial epithelium without inflammatory reaction in the mucosa (one-year result), C, focal parenchymal cellular reaction, with alveolar wall reaction and macrophage catarrh (one-year result!. D. gtass-nber-fiHed macrophages, occupying alveoli whose walk show no significant reaction (result at 18 months). 01 501 1584 8 COMMENT Tltr>r ihtratrnchcal and inhalation studies with wi*| have confirmed fairly con vulsively tlwu glass is not fihroKenic when retained in d Inn** fissue. Ai the same time the gravity of the tvjte of bronchial lesion provoked iteW'>ltafes vautirm in dismissing gJns-* wool as itmoctwws. Indeed, it should 1* retarded as a pmcmially harmful sub stance in circumstances leading to the inhala tion o* large <|unntitles of the type of prod uct studied In these experiments. Other nwMlern types of glass wool or fi1>er glass my nor lave any comparable effects. hi +evcml respects, tlte pulmonary reactn to glass wool is similar to that produced by aslte>tn.< filters. which the glass spicules resemble. However, despite the prominence <f glass spicules in the lung tissue, no "glasswool bodies'* were observed which could be compared to "asbestos bodies." It is there fore not the shape alone of the asbestos fiber which leads to the formation of asbestos bodies. It is to be noted also that asbestos fibers are intensely fibrogenie, whereas the lung tissue reacts to the glass fibers by means of a cellular response chiefly. This contrast again emphasizes the tan that the physical resemblances between glass wool fibers and asbestos do not determine their respective pathogenic propensities. Obliterative damage tc the bronchioles and the proliferative reaction of the bronchiolar and bronchial epithelium are ob viously the more im^>ortant lesions caused by the glass wool. There is but a limited range of substances which can provoke epi thelial hyperplasia in experimental animals,4 and the specific effect of glass wool thus extend** the list. The significance of this observation in relation to unctvtfenesi?* u-rds further clarification. SOIMA*Y AND CONCLUSIONS When introduced rntratracheally. longfiber, medium-caiil>er glass-wool dust pro vokes early marked bronchtolar damage, which persists tor more than a year without leading to well-defined fibrosis. Some of the glass wool is transferred to the hilar lymph nodes where it accumulates without inducing local fibrosis. Inhalation of short-fiber, medium-caliber glass wool produces a retarded pulmonary reaction, comprising partly an interstitial pneumonitis but dominantly an endobronchiolar and peribronchiolar lesion. A tendency toward bronchial epithelial hyperplasia arises under the influence of pro longed short-fiber, medium-caliber glass-wool inhalation. REFERENCES 1. Dhcr*. V.: {.'Industrie de la fibre <k verve. Arch, mal. profess. 7:19-23. 19*6. 2. Pellem, J., and Couden. La dermatose <Je la lame d vrrre, Arch, mat, profess. 7:23*27, 1946, 3. Roche, L,: Le danger polmonaire dans ('Industrie de* fibres de verre. Arch. mal. firclesv 7:27-28, 1946. 4. Kahfau. G.; Todltche Pfietmvoate nach Gas* staub inhalation durch Verarbeitung eines Kanst* stones aus Glaswoile. Frankfurt. Ztxhr. S#:!4t* ISO. 1947. 5. Scheperi, G. W. H., and Delahant, A. B.. An Experimental Study of (he Effects of Gas? Wool on Animal Lungs, A. M. A. Arch. lndui Health 12:276*279. 19*5. 6. Schepers. G. W. H.: Tlte Btoluglcaj Action of Tungsten Carbide and Cobalt: Studies on *> j'enmemai Pulmonary Histopathologv. A. M. A. Arch. Indust. Health 12:140-146. 1955. f'luhJ OHi Pfibhikei in ifit Cnilfd Suttl of 01 501 1585