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vM-UV. S3S"` The THIS DOCUMENT WAS NOT A RECORD OF PPG INDUSTRIES, INC. DID NOT COME FROM jsyfiasss?:?*. * /V:"pj ; f! INC.\ ;yS^wi ww , . , - ;, ' J 5 * 5 , V^.r ' ' * *1 Journal lisf cthe V'.Tf ILES American Medical Association Vol. 114, No. 7 Published Under the Auepieee of the Board of Trustees' CorYUtCHT, 1940, v AwaatcAX Uidicjo. Association Chicago, Illinois February 17, 1940 with quartz, but it is probably the latter which is respon THE PATHOLOGY AND ROENTGEXOGRAPHIC MANIFESTATIONS OF PNEUMOCONIOSIS sible for pulmonary damage. Hence reactions to such dusts are properly designated as modified silicosis. Pos sibly other silicates whose effects have not yet been evaluated may subsequently prove to lie dangerous in LEROY U. GARDNER, M.D. SARANAC, N. Y. their own rights, but if they are it will not be because they are compounds of silicon but because of some special peculiarity of structure or composition. To the pathologists who -coined it. the term pneumo In the temporary category are the pneumoconioses coniosis was useful to describe all pulmonary reactions that are known chiefly from shadows cast on a roent due fo the inhalation of dust. Under the impetus of genogram. They may have a foundation of pathologic compensation laws this group of conditions has received reaction, but it has not yet been adequately defined. so much attention that today pneumoconiosis is almost However, the changes in the film are associated with a household word. But too few are aware of its origi so few authentic symptoms that their influence is viewed nal significance and even some medical writers use it with skepticism. Here belong the so-called baritosis interchangeably with the specific term silicosis. As a seen in men who are exposed to dust of barium sulfate, pathologist I prefer to retain the original meaning and and the false nodulation of arc welders. The former, use pneumoconiosis as a generic term to describe all described by Arrigoni,2 may be nothing but the shadows forms of pulmonary reactions to inhaled dust, with no of compact collections of radiopaque barium particles * implication as to character, severity or effect on func in the lungs. Likewise, Enzer's * report of a single tion. The two clinically important forms of pneumo autopsy on an arc welder makes it seem probable that coniosis that are known as silicosis and asbestosis are similar collections of iron particles rather than foci respectively due to inhaled free silica and ashestos dusts. of fibrous reaction are responsible for the "nodular'' Other forms have been given special names to indicate shadows seen in occasional roentgenograms. the kind of mineral that produces them, but such terms Finally there is the whole group of reactions to have little practical significance because most pure sub .organic dusts that are properly included under the term stances other than free silica and asbestos cause little pneumoconiosis. One form said to be due to cotton irritation and provoke essentially the same kind of tissue filler has been named byssinosis but no good description changes. Available information would make it more of its pathologic manifestations can be found in the logical to classify most of the other known pneumo literature. In general jt is assumed that most of the conioses in two general categories. Those which are organic dusts may cause bronchitis with or without characterized by appreciable degrees of fibrosis will sensitization phenomena resulting in a variety of allergic yield free silica on analysis and hence should be desig symptoms. Moreover the reaction to dust composed nated as "modified silicosis." For the remainder I of living organisms is in one sense a pneumoconiosis, would suggest the name "benign nonspecific pneumo but such conditions are generally classified as infections. coniosis." They are beyond the scope of this paper. Likewise, Illustrative of the latter are simple anthracosis and definitely toxic dusts such as lead are excluded. Even siderosis produced by inhaling relatively pure coal or without this group it will be .appreciated that the term . . iron dusts. By themselves these minerals provoke no pneumoconiosis includes many different conditions and | | significant fibrosis but merely pigmentation, which has does not necessarily imply disabling disease of the no influence on pulmonary function. When they are lungs. ' I I } I mixed with free silica there is a fibrous-reaction, but The first paper of the series4 dealt with specific J J it is due to the contaminating silica. The resultant dis causes. It reviewed sonic ofthe complex factors which ( 0J eases are then more properly designated as anthraco- govern the behavior of fine mineral particles suspended I o i silicosis and sidcrosilicosis. in air and attempted to pointout how they influ- J m | Badham1 suggested the term "silicatosis" to desig-. enced the inhalation of dust. It discussed the varying kiate reaction to any silicate dust, but as there are hun capacities of different kinds of minerals to provoke i no i J __ J dreds of different silicates and only the fibrous varieties, reaction once they had accumulated in sufficient quanti collectively called asbestos, are known to provoke seri ties within the lungs and indicated that some might ous reaction his suggestion has not been generally inhibit the dangerous effects of free silica.. It con-pP I r` i adopted. In nature some silicates are commonly mixed sidered the influence of coexistent infection and thi> J 1 ^ I From the Saranac Laboratory for the Study of Tuberculotit of the Edward L. TnideauFoundatioa. 2. Arrictmi. Arturo: Pntumnrw.irt.1, r 536 PNEUMOCONIOSIS--GARDNER subject of individual susceptibility with a review of the factors proposed to explain this phenomenon. The present paper will be concerned with the patho logic reactions to different minerals in normal and in infected human lungs. It will take up the evolution of the various disease processes and, when possible, describe the shadow pattern cast on roentgenograms of the lungs. PROTECTIVE MECHANISMS When one considers that in quiet respiration the average human being inhales some 12,000 liters of air every twenty-four hours and then recalls the varying degrees of atmospheric pollution created in our indus trial civilization, it is apparent that the lungs must be protected against dust or they could not escape becoming clogged with foreign material. In all the higher ani mals, at least, two sets of mechanisms have developed designed to keep their lungs clean: one prevents dust particles from entering the lungs; the other removes the particles that elude the first barriers. Dust particles are caught in the mucus secreted by the membrane lining all parts of the tract. Ciliary action then transports them to the nasopharynx, from which they are excreted. Lehmann * has suggested that such activities play only a minor role in the removal of dust in the nose and thinks that the shape of its cavities has much more effect. He has pointed out that the nasal passage con sists of dilated anterior and posterior portions separated by a narrow constriction in the vicinity of the turbinates. He recalls that when dust-laden air is blown through a glass tube with a central constriction the particles all come to rest in the distal, dilated portion owng to the sudden cooling and expansion of the air. He believes that deformities due to faulty development, disease or injury change the shape of the nasal cavities and lower their efficiency for the removal of foreign particles.' The technical difficulties encountered in mea suring the quantities of . dust retained in the nose have prevented confirmation of his. observations. It is generally assumed that at least half of the for eign matter in inspired air will be removed by these mechanisms in the normal nose, trachea and bronchi. There has been considerable speculation but little proof of the influence of disease in these organs. It is argued that the chronic bronchitis often associated with silicosis probably permits unusual quantities of dust to enter the lungs. As a matter of observation, the lungs of animals with purulent bronchitis actually contain much less dust than those of normal ones exposed to the same concen tration. The heavy plugs of secretion in the larger air passages mechanically prevent the ingress of foreign particles. It has also been pointed out that one of the manifestations of chronic bronchitis is epithelial meta plasia with the formation of a smooth lining membrane that should permit freer passage of dust particles into the lungs. One should remember, however, that such metaplasia is practically never generalized and that it almost always involves one or two bronchi immediately adjacent to a focus of chronic disease inside the lung. Such a condition might account in part for the unusu ally heavy deposits of dust in the localized pulmonary focus of infection, but it would have little influence on the rest of the lungs. Thus sonic phases of tracheitis and bronchitis may be protective mechanisms, and until their influence has been evaluated it is best to refrain from inference. The discussion thus far has dealt only with particulate foreign bodies, but where fibrous materials are con cerned the upper respiratory protection would seem to be less adequate. Since asbestosis constitutes one of the dangerous forms of pneumoconiosis to be discussed, certain exceptions to what has been said must be noted at this point. Apparently many of the long asbestos fibers succeed in sliding over the surface of ciliated epithelium, for the lungs contain plenty in excess of from -10 to 20 microns in length, and occasional ones as long as 200 microns have been discovered. These fibers seem to pass through the smooth walled bronchi quite readily, but when they reach the respiratory bron chioles the alveolar pouches given off from the sides of these tubes entrap and retain them. Whether the same is true of till fibrous foreign bodies has not been established. Little is known about the primary distribution of inhaled foreign particles within the lungs or the factors which govern it. .' It has been observed that carmine particles reach the subpleural alveoli within half an hour after animals have been exposed to heavy atmospheric suspensions of such material. The path of these pani cles, the influence of tidal and residual air, the effect of deep or shallow breathing all remain to be investi gated. Posture and specific gravity probably have little influence on particles as small as 3 microns or less in diameter. Secondary deposition of inhaled inert particles, on the other hand, has been investigated more extensively. Gross inspection of the lungs often shows streaks of pigmentation in the pleural surface, arranged in bands that are opposed to the intercostal surfaces, with little or no deposit in the intervening grooves formed by the ribs. ' Likewise the diaphragmatic surfaces are prac tically free of dust. Such distribution implies that pres sure of overlying.parts has prevented local deposition. Furthermore the heaviest deposits tend to occur in the upper two thirds of the pleura, suggesting that the greater excursion of. the lower portion of the lung may have limited retention. . Examination of a section of the lung is not so informative because the various struc tures are cut in so many planes. However, inspection with a lens will usually demonstrate fine linear deposits along the connective tissue septunis, between lobules and around the medium sized blood vessels. The walls of the bronchi always show much less pigmentation. In very severe cases of pure anthracosis the entire lung may be uniformly black. Almost always the lymphoid tissues within the lungs and those of the nodes' at their root are more or less heavily pigmented. To understand this distribution of inhaled pigment one must appreciate the mechanisms provided for its elimination from the air spaces. These mechanisms include the mobile alveolar phagocytes and the pulmo nary lymphatic system. Alveolar Phagocytes.--These originate in the walls of the air spaces, become detached and are capable of independent ameboid activity. Their origin is still debated, but it is my own belief * that they belong to the general group of wandering cells of connective tis sue, variously known as histiocytes, clasmatocytes and the like. Others think that they may be modified epithe lial cells from the alveolar lining and some observers consider them monocytes that have wandered out of the blood vessels. This is not the place to discuss the evi dence for these views. Whatever their origin, these 5. Lehmann, Gunther: Die Ftherung Btdttuunif fur Staubkrankhetten, Berlin, Jut | BB 000T099 | NOT HfiMF FROM PPnTil re T.: The Origin of the Alveolar (Sept) 1927. 8?nr, it 51 j j Voti'm 114 PNEUMOCONIOSIS--GARDNEJfaT rr. - - Xcmit 7 mil LUi.it rvsUid i-VG FILEcells appear iu the alveoli in numbers corresponding to the areolar tissue until it can be carried off through the quantities of inhaled foreign bodies. As chance the lymphatic vessels or whether, having entered a contacts are established, the particles of dust are vessel at some peripheral point, it lias subsequently ingested by the cells.7 The process may be repeated escaped into the surrounding tissue. In any event so often that many phagocytes contain enough foreign such deposition occurs in the pulmonary framework, material to obscure their internal structure. Often the a location where the foreign body can exert no influ cell enlarges'as it engulfs more particles. The phago- ence on respiratory function. .cyte moves slowly over the inner surface of the air space These perilymphatic and lymphoid tissue accumula until it finally comes to rest in the vicinity of a lymph tions of particles are responsible for the pigmentation vessel. Whether there is any force which guides its seen on gross inspection of tire lungs. On the pleural course has never been established. surface the delicate tracery of lines is made up of Lymphatic System.--The final stage in the process accumulations in the .areolar tissues about the super of freeing the air spaces of accumulated foreign par- ficial lymph vessels; the focal collections occur in tides is a function of the lymphatic system. Space lymphoid tissues at the junction of communicating and forbids a' complete description of the pulmonary lym superficial lymph vessels. Similar relationships exist phatics but it should be recalled that the lungs are pro in the depths of the lungs. The generalized diffuse vided with two sets of lymph vessels, one coursing pigmentation often seen'in the lungs of persons dying through the pleura and another located in the connective during exposure to dust'is due to free and phago- tissue sheaths of blood vessels and bronchi. The super- cytosed particles still within the air spaces. In cases fidal and deep sets communicate with one another by in which diffuse pigmentation is still present years means of short thick vessels situated in the septums between subpleural lobules; these permit lymph to flow from the interior of the lung to the pleura in case of obstruction in the deep system. Wherever lymphatic trunks communicate with one another inside the lung there are masses of lymphoid tissue. These points are located in the pleura, at the distal ends of tire alveolar after exposure' has ceased, the "drainage" mechanisms have been inadequate to remove the excess of inhaled particles. However, the next section will indicate that even within the air spaces most kinds of particles produce no apparent changes that could interfere with respiratory function. ducts and where blood vessels or bronchi bifurcate. The THE HISTOGENESIS OF PNEC.MOCONIOSJS lymphoid nodules increase in size as the hilus is approached. Both superficial and deep lymphatics dis charge most of their lymph into large nodes located about the bifurcation of the trachea, referred to in this communication as the tracheobronchial nodes. Efferents from the lower portion of both lungs pass through the crura of the diaphragm to nodes situated along the esophagus and cardiac end of the stomach. Dust particles are carried into the lymphatic vessels either by mobile phagocytes or in the free state. The mechanism .in the latter case is not understood.* Many come to rest in and about intrapulmonary lymphoid deposits; more are borne along and deposited in the tracheobronchial nodes. In experimental animals the first deposition is in the nodes, and as these structures become filled increasing quantities are found in the successively peripheral nodules of pulmonary lymphoid tissue. Strachan and Simson * described similar deposi tion in human lungs. Not all the inhaled material is removed to the lymphoid tissues; in most lungs considerable pigment is also found in the areolar tissue surrounding the lymph vessels. These deposits often seem to be made tip of elongated collections of free particles, packed between the fibers of connective tissue. Havthom, *" however, has demonstrated that many of these par ticles are actually contained within the bodies of com pressed phagocytes. On production of an edema that separates the fibers and allows the "dust cells" to assume their more familiar spherical form, the intra cellular distribution of the particles again becomes recognizable. It is not known whether such perilymphatic deposits are composed of material that is temporarily stored in Phagocytosis and Concentration of Dust.--It is in the phagocytes that foreign bodies first exert their specific influences on living cells and that differences due to physicochemical composition of the irritant become manifest. Inert substances like garnet, silicon carbide and aluminum oxide have no effect on the structure of the cell, although they may retard or stop its locomotion by their mass within its cytoplasm. Fre quently such overloaded phagocytes are found within the alveoli years after exposure to dust has ceased." Toxic free silica, on the other hand, quickly injures the phagocytes, and its effect is directly proportional to the numlrer and size of the ingested particles. Such effects are most readily observed in experimental animals killed at intervals during exposure to high con centration? of siliceous dust, but they can also be seen in human cases of rapidly developing silicosis. No changes are visible in the cell that lias taken up a few large fragments 4 or more microns in diameter, but when the particle size is under 3 microns the number ingested by each cell is much greater and, as a conse quence. the amount of surface in contact with cytoplasm is greatly increased. Degenerative changes closely simulating those in the "epithelioid" cells of tuber culosis then become manifest. The cell enlarges, drop * lets of visible lipoid appear in the cytoplasm and the elements stained supravitally with neutral red arc rear ranged to form patterns indistinguishable from those in tuberculous epithelioid cells.11 With the proper con IS; IS centration of the irritant, the nucleus divides repeatedly as the cytoplasm increases in extent; the result is a / i giant cell in every way comparable to the Langhans / I giant cell of tuberculosis. In animals injected with .extremely fine silica, such giant cells may attain a. JV. 9\: Phagocvtori* of Solid Particle*. J. Gen. phytic]. *' 2 k*!* (March) 1921, UnnkeT, C. K., and Field. Madeleine E.: Lymphatic*. Lymph and iUMie Fluid, Baltimore, William* Si Wilkin* Company, 1933. Sirnehan. A. S., and Simjon, F. \V,: A Preliminary Study of the ratuolOEy of s,]lco(;f a* Seen on the Witwater*rand: Silicosis, Inter- toil Co**fTMre at Johanncfbure, Geneva. 1930, pp. 221-248. i `-TV"??TM9* S. R.: Experimental Edema a* an Aid to Hittapatho- '"e>e Studie*, Warthin Ann. Yol., pp. 49I-S02, 1927. astounding size with several hundred nuclei. Under very potent stimulation the cell is killed and undergoes 11. Gardner, I, V.: Studie* on the Relation of Mineral Du*t* Yo^ Tuberculosis: III. Carborundum, Am. Ret. Tuberc. 7:344*357 (July) 1933. , 12. Gardner, anil t.: Tbe a Similarity of b..L *tmhe- Lesions Produced by Silica IT i 53S PNE UMOCONIOSIS--GARDNER Jot;a. A. M. A. Fa*. 17, 1940 a process that Mavrogordato ** described as "mummi fication." It retains its normal size and the limiting membrane is intact, but all internal structures fail to stain with histologic dyes. Some of these "ghost cells" preserve their identity, but others probably break up and liberate their contents, which are then taken up by new phagocytes. The great similarity between the effects produced by crystalline silica and tubercle bacilli11 * h*as puzzled many observers, but Fallon 14 1h5as proposed a hypothesis and already published preliminary experiments which may contain the explanation. He conceived the idea that the action of both these primary irritants on the phagocytes liberates toxic phospholipids and that these substances are responsible.for the further proliferation that " results in the formation of the granulomatous nodule. He demonstrated that such lipids, at least par tially freed of silica, were actually capable of producing tubercles. Finally there is a suggestion that small quantities of silica taken up by phagocytes tend to stimulate ameboid activity,1* for in early silicosis the cells seem to migrate to lymphoid tissue more rapidly than in any other form of pneumoconiosis. However, it is difficult to be certain whether the clusters of cells observed in and about the nodes have actually migrated there or whether new ones may have proliferated under the stimulation of the toxic material. The response of the phagocytes to fibrous asbestos requires special comment, as it is treated in a different manner from particulate material. The fibers are often too long to be completely ingested by a mononuclear or giant phagocyte. Frequently one end will project beyond the border of the cell, or sometimes several phagocytes will attach themselves to a single fiber. Giant cells do not migrate far and most of them are either applied to the walls of the bronchiole or at most have penetrated its substance. It is practically impos sible to discover fibers or asbestosis bodies in the more remote intrapulmonary or mediastinal lymphoid tissues. For all dusts the mechanisms of phagocytosis and concentration have many common features but, as indicated, even the initial cellular responses are modified by the properties peculiar to the three classes of minerals under consideration. Because these changes are micro scopic, it has been convenient to consider them together. We are now in a position to consider the three generally recognized anatomic forms of reaction to mineral dusts under the headings benign nonspecific pneumoconioses, silicosis and asbestosis. THE BENIGN NONSPECIFIC PNEUMOCONIOSES In the category of benign nonspecific pneumoconiosis is included every known reaction to mineral dust except that to the soluble poisons such as lead, the specific diseases, silicosis and asbestosis, and "roentgenologic conditions" such as baritosis and the pseudonodulation of arc welders, previously mentioned. We have seen that the action of the alveolar phago. c\*tes and the lymphatic system tends to concentrate particulate mineral matter, regardless of its chemical composition, in the lymphoid tissues of the lungs and mediastinum and that there are also appreciable accumu lations in the areolar tissues about lymphatic trunks. 1J, Mavrojorrtato, A.: Studiei in Experimental Silicosis and Other Piieiimonokuntoses, South African Institute for Medical Research, No. 15, 19**i pp 1 14. Fallou, J. T.: Specific Tissue Reactions to Phospholipids: ASupRested Explanation for the Similarity of the Lesions of Silicosis and Pul* nionary Tulierculosis. Canad. M. A. J. 3i 223-228 (March) 1937. 15. Gardner, L. U,: Studies on Experimental pneumoconiosis: VIII. Quartz Dust, J. Indust. My*. 14: 18-37 (Jan.) 1933. The reaction that will be produced in these locations is determined by the physicochemical properties of the minerals concerned. As shown in the first paper, on etiology,4 most of them exert no appreciable effects on connective tissues; a few can produce low grade chronic inflammation which is not progressive and does not terminate in fibrosis appreciable on gross examination. All these reactions occur in the framework of the lung. The only secondary effect is the dilatation of the few air spaces that directly abut on the pigmented connec-^p live tissues. Such emphysema never involves othef parts of the lung and is too restricted in extent to have func tional significance. , *'"; Gross appearances are determined largely by the. color of the inhaled dust'. If it has no color, no abnormality may be detectible. If in masses it appears black, the diagnosis, will probably be "anthracosis" in the absence of a history of exposure to a specific kind of mineral; really it makes little difference. The pleural surface of the lung is flecked with focal and linear deposits of pigment. The cut surface shows the linear collections ih the septums between lobules, the thin streaks along branches of the pulmonary arteries., and the rounded flecks scattered here and there whidr a -lens identifies as perivascular accumulations about cross sections of arterioles. The air spaces are always visible in the colored areas, a feature which distinguishes.'.`. the benign pneumoconiosis from all silicotic reactions.*- - Both the intrapulmonary' and the mediastinal lymphoid " tissue stand out in sharp contrast by reason of their- color. In extreme cases the pigmentation is diffuse and the entire pleural and cut surface of the lung may be black. But in no case is there enough reaction to be detected by palpation or gross inspection. The shadows cast by such changes on a roentgeno gram tend to exaggerate their importance. Except in the most advanced cases the pattern is merely one of exaggeration of the normal lungmarkings. Since most of the latter are due to the blood vessels, their shadows become heavier and the finer branches are visualized when they are thickened by a sheath of dust and chronic inflammatory reaction.^In advanced cases the film may present a reticulated appearance due to the thickening of peripheral arterial twigs and the inter lobular septums. The diffuse haziness observed in certain cases may be caused by the presence of great numbers of phagocytes scattered throughout the air spaces. Enough of them in superimposed planes of tissue will intercept some of the x-rays and register a haze on the film. Since the blood vessels may be thickened from causes other than deposits of dust in their outer coats and since such thickening becomes increasingly' fre quent with advancing age,1* there is a great possibility of error in ascribing the exaggerated linear markings seen in a film to occupational factors. In older per sons particularly one must beware of diagnosing benign nonspecific pneumoconiosis from a roentgenogram and a history' of exposure to dust. It is hard to imagine that pulmonary symptoms or disability could be produced by jeactions of this char acter. There is' generally no involvement of the alveolar walls at all. While in advanced cases there may be a little emphysema, it is confined to only a few air spaces immediately about the pigmented connective tissues of the lung. Even in extreme cases presenting 16. Gardner, L. U.; Durkan. T. M.: Brumfiet, D. M., and Sampson. H. I..: Survey in Seventeen Cement Plants of Atmospheric Dusts Their Effects upon the Lungs of 2,200 Emplojeea, J. Indust. ib'S 'V Toxicol. SX: 279-3IS (Sept.) 1939. _____________ G J I BB Q007101_2 ) VoLL'MC 114 Kimil 7 PNEUMOCONIOSIS--GARDNER 539 diffuse pigmentation the lung is still elastic and the chance in four that the disease will subsequently respiratory membranes show no abnormality. If progress to nodulation. Others will argue that the symptoms are associated with such reactions they are history should be given more weight, and they would in all probability due to causes outside the lungs. call such'cases presilicotic. As far as can be learned from statistical and experi If silicosis in this early state is not definitely diag- mental evidence, the dusts other than free silica are not nosable during life, has it any significance? Will it responsible for alteration of natural susceptibility to progress ? Does it increase susceptibility to - tuber tuberculous infection. There is no proof that their culosis? The probabilities of progression to a stage inhalation increases the probability of infection with other organisms. In some of the dusty trades, investi gation is disclosing that other factors than the dust are responsible for pulmonary infection. - - 1 L - Scars or imperfectly healed inf^ctibtls in the lungs of persons exposed to these inert or practically inert minerals are sometimes a cause of confusion. They attract and retain abnormal quantities of inhaled dust particles and it is possible, though not yet proved, that such deposits may maintain a preestablished chronic inflammatory reaction. Hence there may be less con of generalized nodulation are slight if the exposure should be interrupted at this stage. This is not neces sarily true in the case of a worker such as a sand blaster whose-exposure'has been.-heavy, and who has attained the stage of linear exaggeration rapidly. With ordinary exposures, however, there would not be enough silica accumulated in the air spaces to produce fresh nodules if no more dust were inhaled. With regard to susceptibility to tuberculosis, statistics on groups of men exposed to relatively high concentrations of silica show a slightly higher incidence of this infec oo U u. u ' cr o. ttv.:. o traction and less tendency for the area of disease to disappear. Such an outcome is not inevitable, but many more cases will have to be followed in serial roentgeno tion in those with exaggerated linear markings than in c: those with no risible evidence of reaction to dust. The odds are against a silicotic origin in an individual case, CO grams before its frequency is established. but it could not be proved that silica was not a factor, Much more puzzling are the patients with obvious particularly when atmospheric concentrations of this fibrosis whose history records only exposure to inert mineral may have been high. a minerals. In most of these instances a review of the facts and a chemical examination of the tissues will disclose that there has been free silica either in the last or in previous exposures. An apparently comprehen sive occupational history and the histologic evidence of a single autopsy specimen does not warrant the infer ence that a mineral other than free silica has caused the fibrosis. Quartz dust masquerades in unsuspected places where much ingenuity may be needed to detect it. If there is no probability of progression or no increase in susceptibility to tuberculosis, does early silicosis of this degree have any influence on the body? The only effect thus far discovered is the increased probability that continued exposure to silica dust will ultimately result in more advanced stages of silicosis. The latter raises problems of administration, the answers to which depend on local conditions and the status of the subject. If the individual is young and K:- SILICOSIS Initial Phase.--As already intimated, silicosis begins like the reaction to any other particulate dust, but the peculiar properties of free silica are responsible for subsequent modifications of the standard pattern. Migratory phagocytes concentrate silica in and about the lymphatic system of the lungs. The toxic par ticles, directly or indirectly through the -released lipoids, linear exaggeration has developed quite rapidly in an environment heavily polluted with free silica dust, he should probably be transferred to some other position. If he is older and serial roentgenograms have shown that such changes have been present for a long time, he can unquestionably remain where he is, especially when an enlightened management is making every effort to reduce the concentration of dust in the working stimulate connective tissue cells in their immediate atmosphere. His roentgenographic changes may be due vicinity and proliferation ensues. The ultimate result to other causes and hence will not progress because of is a nodule composed of.connective tissue whose fibers these conditions. are characteristically modified by the effect of the At this stage of the disease there is no disability or silica. The location of these nodules, situated in the any limitation of respiratory function because the .' ' . immediate vicinity of the lymphatic trunks, impedes lesions do not encroach on those portions of the lung the free flow of lymph. Such a development of micro in which respiration Occurs. If physical examination scopic silicotic nodules in the tracheobronchial lymph discloses evidence of disability, the cause must be found . ( -- j nodes and intrapulmonary lymphoid tissues constitutes outside the lungs. t .t ! the primary phase of silicosis. Discrete Nodulation of Classic Silicosis.--After Grossly these early nodular lesions are invisible or enough silicotic reaction has developed in the lymphoid joj jj recognizable only with a magnifying glass. Usually tissue to retard the flow of lymph, fresh increments of j o | i there is enough carbon or. other colored dust inhaled inhaled Silica are not as readily removed from the * 12 j with the silica to produce the linear and focal pigmen pulmonary air spaces. The phagocytes still ingest par- { t tation previously described for inert nonspecific pneu moconiosis. Obviously a roentgenogram of such a lung will reveal the shadows of the perivascular desposits but not those of the nodular lesions that are too small to be seen without a microscope. tides and migrate with them over the sdrface of the alveolar lining. Unexplained conditions in the lym- phatics (possibly increased lymph pressures) now seem to prevent the cells front entering the vessels. As a ; matter of observation, most of them collect in groups II | 03 J i --i . ----- A history of exposure to a dust rich in free silica scattered here and there on the walls of the air spaces. - --. with a roentgenogram showing only exaggeration of Again the high local concentration of silica results in the linear lung markings presents a problem in diag proliferation of connective tissue cdls. Parenchyma* ~~ ^ nosis. I myself belieVe that if other causes can be tous nodules now develop, which ultimately attain a 4 eliminated the case should be classified as a benign diameter of 3 or 4 ntni. They are characterized by the ^ nonspecific pneumoconiosis, for there is nothing pathog sharp definition of their borders, by their uniform ( r~i nomonic about the filfn and there is at least nnlv one rnmnosition of hvaline cnllasren fibers arranged either 540 PNEUMOCONIOSIS--GARDNER Joe*. A. It. A. r*. i7, in concentric laniinas or in coarse basket weave and by quite harmless, is apt. in the silicotic lung, to result in their regular distribution throughout all parts of both chronic progressive infection. Obviously such con lungs. Certain variations are encountered, but these do tacts cannot occur unless there are open cases of tuber not cause difficulties in diagnosis. The centers of culosis in the locality. In areas in which general living young nodules may be necrotic when the disease conditions have improved and routine antituberculosis evolves rapidly. Peripheral accumulations of non- hygienic measures have been put in practice the tuber siliceous dusts may cause a fringe of more cellular culosis rate has fallen, among the silicotic as well as connective tissue that more or less modifies the usual among the other members of the community. sharpness of the border. The costophrenic portions of The case for nnntuberculous infections is not so the lungs may contain no nodules owing to the develop clearly documented and today it would be well to turn ment of emphysema in these areas subsequent to the back to Collis's Milroy Lecture of 1915," in which he contraction of the many fibrous foci in other parts of the took great pains to show that pneumonia is relatively lung. In the early case the tracheobronchial lymph uncommon with silicosis though prevalent with "the nodes are enlarged, but as the scar tissue contracts pneumoconioses that cause bronchitis." Other statis i they shrink and become exceedingly hard. tics were published subsequently, however, that showed The shadows of these larger nodules uniformly dis high frequencies of pneumonia in different dusty trades, tributed throughout the parenchyma of both lungs and autoposies on silicotic subjects demonstrated the form a characteristic roentgenographic pattern. When common occurrence of massive areas of fibrosis which associated with a history of adequate exposure to closely simulated the end result of an organized pneu silica dust and an absence of any very marked physical monia. Most observers came to believe that the same signs, such a film constitutes an adequate basis for the mechanisms which increased susceptibility to tuber diagnosis of silicosis. Clinicians generally classify culosis also favored the growth of pneumococci and cases of silicosis in three stages, defined by the number other bacteria. Thoughtlessly silica was accepted as and size of the nodular shadows. In stage 1 the linear the common etiologic factor. markings are markedly exaggerated and the nodulation But new investigations of silica industries showed is barely visible: in stage 2 the linear shadows are that excessive pneumonia rates did not prevail in all obscured and each nodule is from 2 to 3 mm. in of them. Then the importance of exposure to extremes diameter; in stage 3 the nodules measure from 3 to 6 of temperature, humidity and the like assumed proper nun., are less well defined and show a tendency to con significance in the silica industries. as in others. In fluence in certain areas. There is generally a suspicion mining groups it was shown that the pneumonia rate of associated infection in films interpreted as stage 3. dropped to approximately that of the local community -The clinical significance of generalized discrete sili when the change house was moved to the head of the r cotic nodulation is not nearly as great as inspection of shaft so that the sweaty, overheated miner no longer ii . the film might indicate. Roentgenographic surveys had to expose himself to winter weather on coming to always reveal many cases which have developed entirely the surface. Similarly it is now believed that in the unsuspected by the subjects, who have continued to foundry the influence of sudden changes of temperature perform their habitual work with no symptoms of is much greater than the silica dust, to which only a respiratory embarrassment. Only shortness of breath few of the employees are exposed in dangerous concen on sudden and unusual exertion demonstrates that the trations. In many modem mining areas the incidence respiratory reserve has been reduced. In other words, of pneumonia is no higher than that in the general there is still so much uninvolved lung tissue that normal population, and the course of the disease when it does respiration is unimpaired. Persons with nonclinical develop is usually normal.19 jIi- silicosis are not disabled and from a medical point of view are employable. Since they are usually skilled by virtue of long experience, the management would gen Pathologic material uncontrolled by a knowledge of general clinical experience may be misleading, owing to selection of cases submitted for examination. It may erally prefer to keep them at work. However, liability for compensation has complicated the picture and has been responsible' for a lamentable rejection of many able workmen. The nodular stage of-silicosis is associated with a definite increase in susceptibility to tuberculosis. This is attested by the old South African figures, which showed tuberculosis of the lungs in 75 per cent of the silicotic miners who died. In the Saranac Laboratory autopsy series active tuberculosis was present in 65 per cent of the lungs of persons exposed to free silica dust and in only 15 per cent of those working in other dusts. Official figures from the Factory Department of the British Home Office1T disclosed evidence of tuberculosis in 59.4 per cent of the autopsies on sili cotic subjects. well be true that some of the massive conglomerate foci seen in lungs are the result of organized pneumonia, but serial roentgenograms of certain silicotic groups make it appear doubtful whether organization is the common outcome. Experiments by Yorwald, Delahant and Dworski -u show that in rabbits silicosis alters in no way suscepti bility to type III pneumococats or the course of the resultant pneumonia. It is anticipated that similar tests will be made with other types of this organism. Until accurate statistics based on reliable clinical and bacteriologic data for pneumonias of different origins become available, it would be unwise to generalize. At the present time, however, American experience does not seem to indicate that silicosis has an appreciably unfavorable influence on lobar pneumonia. Possibly infections due to organisms outside the pneumococcus The infection may develop as a result of reactivation group are in a different category. of a preexisting latent tuberculous focus, but opinion today is unanimous that new infections from without are a more common cause. A contact with the tubercle bacillus, which in normal subjects would perhaps be 17. Meriwether, E. R. E.: A Memorandum on AibestoaU, Tubercle 15i 109-118 (Dec.) J93J. 152*159 (Jan.) 18. Colli*. E. L.: Industrial Pneumonoconiotes kith Special Reference to Dust Phthisis, Milroy Lectures, 1915, Pub. Health *B 1 252-259. 19141915; 2: 11. 1915-1916. 19. Pierpont, D.: Fourth Saranac Lalnratory Symposium on Silicosis, 1939, Employer's Mutuals Insurance Company, Wausau, Wit. 20. Vorwald, A. J.; Delahant. A. B., and Dworski, M.: Silicosis and Type III Pneumococcus Pneumonia: An Experimental Study, to be CLIENT DID J_BB_0007103_ PPG FHESc r.t >, uU r/1 L . ,'i . A. M. A, *. 17. 194) al living jrculosi:e tuber- well as not so i to turn vhich he datively ith "the r statisshowed y trades, ated the is which ;d pneuhe same > tuberjcci and tpted as showed il in all xtremes 1 proper lers. In nia * d oV i longer ming to t in the peraturc i only a conceniddence general it does edge of wing to It may rate foci umonia. groups i is the vorski" -uscepti? of tin- similar sin. ica! and origins lize. At ice doe- Rcfcreius* 2S9t 1914* i Silicon** an*! -I.- ** \'0LVt 114 .Nntiu 7 PNE UMO C0X10SIS--GARDNER 541 Rapidly Developing Silicosis.--Whereas most cases parenchyma although the collagen may not show its of silicosis require at least from three to six and more characteristic hyaline, laminated appearance. The often from ten tp twelve years of exposure for their other minerals in the dust tend to be deposited in the development, there are isolated industries in which exposures of from twenty to twenty-four months have produced a modified form of the disease. Under condi tions that liberate excessive quantities of exceedingly fine pure silica the ordinary protective mechanisms fail interlobular septums and walls of arteries as they would in benign nonspecific pneumoconiosis, but they o GO LU also collect around the margins of the. parenchymatous o -J nodules. The result is a combination of nonspecific pneumoconiosis and silicosis with the specific lesions of *JU to cope with the situation and an unusual kind of each modified by the presence of another type of dust. reaction develops. The initial phase of lymphatic The linear perilymphatic deposits are heavier and tend C3 .-'i involvement is lacking. The overwhelming deposits to be fibrous;, the nodules are larger and lack definition of silica seem to stimulate connective tissues in every because of fringes of cellular connective tissue. Fre part of the lung at the same time, and as a consequence quently projections from the nodules are continuous the alveolar walls become thickened and nodules of. with chronic inflammation about vessels and septums. microscopic proportions develop throughout the pul Reaction about adjacent nodules may replace consid monary framework. The air spaces are filled with erable numbers of air spaces, giving rise to a small actively proliferating phagocytes. Irvine*1 has aptly conglomerate focus. However, patent air spares are described the picture as a "dust pneumonia." always present in the involved area. The fibrosis is Gross examination reveals no nodules risible to the naked eye; there is merely a generalized partial con solidation of the lungs. All the postmortem specimens that Is* have seen have been complicated by infection which completed the solidification of the involved areas. Because the nodules are too small to be seen without a microscope they do not cast discrete shadows on a roentgenogram. Except when infection complicates the picture, the film generally shows little but a heavy diffuse haze because most of the air spaces contain enough air to permit the passage of some of the x-rays. The diagnosis in these cases rests not on the film but on the presence of extreme dyspnea in a case in which other causes have been eliminated and on the history of an exposure to excessive quantities of exceedingly fine and pure free silica. This diagnosis is never war ranted except in the case of unusually severe exposures such as those in unprotected sandblasting or -in drilling pure quartz without the ventilation found in ordinarymining practice. Most of the fatal cases terminate in tuberculosis, as indicated by Middleton's ** summary of English experi ence. Foci of necrosis produced by the excessive concentration of fine silica in the microscopic nodules throughout the lungs furnish the most favorable medium conceivable for the growth of the bacilli. A few patients have succumbed to nontuberculous bron chopneumonias, and very rarely it is possible that the silicosis itself may cause death. However, it should always be remembered that evidences of infection are not uniformly distributed and may be hard to distin guish on gross examination of a lung heavily involved with such a reaction to dust. Review of a few small sections in one of Chapman's14 "soap powder cases" failed to disclose evidence of tuberculosis, but so little tissue was available that the possibility of localized mfection could not be excluded. Modified Silicosis.--When the atmospheric dust is composed of a mixture of particles of free silica with those of other minerals such as coal, iron and various silicates the characteristic nodular reaction is modified jtt varying degrees. When the dust contains enough fee silica, nodular fibrosis develops in the pulmonary never of the massive obliterative type to be described later, in which the tissue is uniformly hard and rubber like in consistency. Generally the roentgenologist does not attempt to differentiate between these modified forms of silicosis and those produced by purer silica. In occasional extreme cases, however, the nodular shadows may lack their characteristic definition and uniformity in size, the vascular markings will be unusually heavy and there may be a background of more or less uniform reticu lation. Susceptibility to tuberculosis may be more or less favorably modified in these cases. In siderosilicosis due to hematite, tuberculous infection in both man and animals progresses for a time and then in many cases heals with the formation of masses of scar tissue. The same is apparently true of anthracosilicosis, which often requires prolonged search to discover evidence of the tuberculous element in the healed focus. In granite silicosis, tuberculous infection is much more apt to progress and terminate in cavity formation with dis seminated infectious lesions. Since most industrial dusts are mixtures, modifica tions of the classic- picture of pure silicosis are the rule rather than the exception. It cannot be too strongly emphasized that both the pathologic and the clinical manifestations of silicosis in different industries are not identical in all details. Observations that are perfectly valid for anthracosilicosis may be inapplicable to miners of other hard rock, gTanite cutters or porcelain workers. Massive Conglomerate Fibrosis.--This pathologic feature of the disease is the common cause of most of the disability in silicotic subjects. Unfortunately it presents vexatious problems in diagnosis and adminis trative treatment During life it may be difficult to differentiate it from the simple conglomerations just described under modified silicosis. In this country and { ""| in South Africa most observers think that massive con- | ^ I glomerate fibrosis is due largely to associated infection. {v ( In recent years I have come to feel that a third essen- j I tial factor may be the presence of minerals other than {0 J free silica. At the present time it is impossible to ll classify all areas of conglomerate fibrosis on an etiologic } cq f I" .; Report of the Commitiion to Enquire into the v--.,J"e vrevtlenee and Origin of Cate* of Silieorit, in the Colony of ,, IP Rhodewa, Salisbury, Government Stationery Office. 193S. feTu 1!"' t* U.-. Patholscy of So-Called Acute Silicosis, Am. J. 1240-1249 (Dee.) 1933. ftddlctoa, E. L-: Industrial Pulmonary Disease Due to tbe Inbala* Huly^l1) *1jf2**^ t0 Silicosis, Lancet 2 s 1-9 (July 4), ^^19^ M" Aeut Silicosis, J- A.M. A. 9St 1439-1441 (April basis. Microscopic examination reveals an element of J o i tuberculosis in 60 per cent of the cases; in the remain- { _j der this feature is either absent or escapes detection because it is obscured by the silicotic fibrosis. Although, most or perhaps all of these massive fibrous lesions may / have developed on a background of tuberculospsph / r [ j 542 PNEUMOCONIOSIS--GARDNER Jot*. A. M. A. Fo. 17, 1940 problem is to recognize the ones in which the infection is still active. For them some form of treatment is indicated. No treatment in use today is ideal, for all of them tend to promote healing by fibrosis and it is the scar tissue that causes the disabling dyspnea. Names were coined by the Miners Phthisis Medical Bureau of South Africa to indicate reciprocal relation ships between silicosis and tuberculosis in these chronic forms of the disease. "Tuberculosilicosis is the modifi cation produced in silicotic lesions by a chronic tuber culous infection." Here the dust factor is dominant. "Siiicntuberculosis," on the other hand, is a clinical term used to indicate that the infectious element is more prominent. On the suggestion of Dr. L. G. Irvine, chairman of the bureau, the last International Silicosis Conference in Genera adopted the pathologic term "tuberculosilicosis" as the standard one to describe this specific chronic lesion. It is not applicable to every manifestation of tuberculosis in the silicotic lung. When the infection develops typically, as it does in ncnsilicotic subjects, the diagnosis should be "silicosis with tuberculosis." Such cases are rare, however. The anatomic picture of massive conglomerate fibrosis is variable, although there are certain features that characterize all such lesions. The involved area is hard and rubber-like, is blue-black or gray-black, has rather sharply defined borders and is practically always associated with high grade compensatory emphysema. If the area ef involvement extends to the surface of the lung there is always chronic fibrous pleurisy with adhesions. Most cases occur in organs showing a background of generalized discrete nodulation, but there are some in which this diagnostic feature is lack ing. In the latter case it is possible that contraction of the mass has drawn most of the original nodules into its orbit and that the more peripheral portions of the organ have subsequently been distended by emphysema. The distribution and extent of the fibrosis varies. The massive scars occur most often in the upper part of one or both lungs. Some radiate from the hilus; some assume the form of wedges with their bases on the pleura; others grow as tumor-like masses in the depths of the lung. They may involve the whole of a lobe and even extend across an obliterated interlobar fissure. The cut surface of the conglomerate focus generally shows' a more or less well defined nodular structure, but at times this is recognizable only with a magnify ing glass. Some show central areas of caseation and cavity formation indicative of their tuberculous origin; others are- traversed by irregular slitlike openings filled with ink)' fluid. The latter have no well defined walls and are not differentiated by color from the sur rounding fibrosis. Microscopic sections reveal nodules embedded in a matrix of heavily pigmented hyaline fibrous tissue that replaces practically all normal pulmonary structures. Blood vessels show high grade obliterative endarteritis and often their lumens are filled with dust-containing connective tissue. The larger bronchi are compressed and distorted. When patent, they present advanced chronic inflammatory changes. Tuberculous reaction may be obvious in widespread caseation, but in cases in which the infection has healed it has sometimes been necessary to search over 200 square centimeters of sec tion to discover isolated noncaseous tubercles. In a few cases even this evidence is lacking, but clumps of acidfast bacilli without cellular reaction arc found in areas of softening. Guinea pig inoculation has supplied proof that the organisms are tubercle bacilli. Examina tion of the black slitlike cavities has generally revealed no suggestion of tubercle and these cavities have been interpreted as areas of anemic necrosis resulting from the obliterative endarteritis. In view of the difficulties' of diagnosis it would appear unwise to draw any conclusions as to the frequency of nontuberculous massive conglomerate fibrosis. The shadows of such changes on the roentgenogram offer an easier problem in diagnosis when they occur on a background of generalized nodulation, When this is lacking even the silicotic nature of the disease may be in doubt. Stereoscopic films may permit visualiza tion of discrete nodules otherwise obscured. Overex posed films may bring put tuberculous cavities in the midst of massive'shadows, but often none can be seen. The behavior of the shadows in serial examinations over periods of years is perhaps the most reliable index of activity of the process. The clinical manifestations in many of these cases may likewise be confusing. Often severe dyspnea is the only prominent symptom. Perhaps there has been no loss of weight. The sputum may be repeatedly negative or on rare occasions prove positive by culture or guinea pig inoculation, but if followed long enough the infection in many of these cases will become mani fest. Toxic symptoms then suggest tuberculosis; bacilli are constantly present in the sputum; roentgenograms may reveal cavity formation and more rapid extension of the massive lesion. When this is the case death from tuberculosis is the outcome, bub the individual in whom the infection has completely healed succumbs to other causes. Cardiac Involvement.--The question as to the rela tionship between silicosis and disease of the heart is still debated. Observers primarily interested in sili cosis who are following the course of the disease in groups of employed workmen are unanimous in their opinion that cardiac complications are not unusually common. They admit that some silicotic patients exhibit symptoms referable to the heart but point out that the age group in which silicosis develops is also the one in which arteriosclerosis and myocarditis are general. The clinician whose experience is limited to the general hospital, on the other hand, is confronted with a selected group of silicotic subjects. These men have applied for hospitalization because they are sick and often about to die; those who are obviously tuber culous may be transferred to sanatoriums. Thus the internist is naturally impressed by the high proportion of cardiac conditions among his silicotic patients. The pathologist's -views are likewise colored by the source of his material. Cardiac complications are rare in ablebodied workmen killed by accidents, but they are not at all exceptional in the older men who die in hospitals at the age of 55 or 60 years. Furthermore, both clini cian and pathologist may form unusual concepts of the disease if their material is drawn from a single industry. For example, the anthracosilicosis of the hard coal miners is especially prone to manifest itself as massive conglomerate fibrosis, and it is quite probable that such disease may cause more cardiac complications than the discrete nodulation of sand pulverizing or.'some other kind of mining. Cor pulmonale is primarily a disease of the right side of the heart resulting from obstruction to the circulation in the lung. One of the most common DOCUMENT DIDT11l *o 50 1_B_000710~7 NOT COMP sr-f'S o'J i"* VSOuLnD*K*X* 1714 PNEUMOCONIOSIS--GARDNER 543 causes of such obstruction is high grade emphysema. autopsy reports, it is felt quite definitely that the Silicosis of the massive conglomerate type is liable, to silica has no etiologic - significance. The only dusts produce such emphysema. No one doubts that many known to cause pulmonary carcinoma are those of the patients with long-standing silicosis complicated by radioactive ores in Schneeberg.** Possibly, as Camp conglomerate lesions caused by associated tuberculosis bell's ,T experiments have suggested, the tar in road finally die of congestive heart failure. But the same dust may also be significant; but this awaits proof. is also true of patients with uncomplicated tuberculosis, and yet one rarely speaks of this infection as a com ASBESTOSIS mon cause of "heart disease." Personal experience It will be recalled that protective mechanisms of and the reports from the literature have convinced me the upper respiratory tract appear to be less effective that in most fatal cases of silicosis the heart is already against fibrosis than against particulate foreign bodies damaged by arteriosclerosis or other causes and that . and that mobile phagocytes do not remove long fibers the presence of a conglomerate area of fibrosis with from the pulmonary air spaces. As a consequence the emphysema merely adds toits burden." At the atltopsy' '" greatest accumulation of inhaled asbestos fibers occurs table hypertrophy of the right side of the heart without in the lumen of the respiratory bronchiole, the point at arteriosclerosis and even greater involvement of the . which they first come to rest. Almost none are foun ` opposite side is a rarity. Clinically no one has ever in the areolar tissues about lymphatic trunks or in tl1 demonstrated evidence of increasing strain on the right lymphoid tissues inside or outside the lungs. ReasorgO 'J.side of the heart as the successive phases of simple for believing that the-stimulus' from inhaled asbestqs__ discrete nodulation make their appearance. Even in may be mechanical rather than chemical have been dis the case of massive conglomerate fibrosis cardiac cussed in the first paper on etiology.4 *. symptoms are relatively late manifestations. Further Microscopic Appearance.--As long as asbestos fiber*-, clinical and pathologic studies will be valuable as far continue to be inhaled, scar tissue develops as as they differentiate between the types of pulmonary gradually thickening sleeve about the respiratory- lesions that are alleged to have affected the condition bronchioles. Either because the bore or the tube is- of the heart muscle. - smoothed out by the obliteration of the lateral alveolfcl Carcinoma of the Lungs and Silicosis.--General or because of changes in the lining epithelium, subset interest in the subject of pulmonary cancer has been quently inhaled fibers then pass on into the alveolae- - responsible for special effort in securing autopsies in ducts. Here a similar sleeve of fibrosis develops, andr - such cases. The discovery of coexistent silicosis or this formerly irregular tube likewise permits fibers tcL , even a benign nonspecific pneumoconiosis has led to pass farther into the lungs. Reaction in the walls o"~ v the deduction of causal relationships that are not sup the terminal air spaces ultimately results in a localized ^ ported by statistical evidence. Vorwald and Karr11 patch of obliterative fibrosis of the parenchyma of the^ collected from the literature the results of roentgeno- lung. ographic examinations of 57,362 persons at work in A random microscopic section through an area of, industrial plants creating dust of various kinds. fibrosis does not reveal a uniform obliteration of every* Although the group contained 12,206 with silicosis, air space. Here and there are many that still contain there were only three cases of cancer of the lung. In air; some are of normal size, some are compressed and the Saranac Laboratory surveys of five different indus many are greatly dilated. These patent air spaces are tries, films of 15,587 individuals were reviewed with apparently supplied by other bronchioles that did not the discovery of 1,357 cases of silicosis. In the total group there were only three cases of pulmonary can cer, one in a silicotic subject and two in nonsilicotic subjects. The authors' most impressive autopsy sta tistics were quoted from the 1930 Report of the Miners' Phthisis Medical Bureau of South Africa. This offi cial publication cites postmortem figures on 4,510 adult males including 3,117 European miners and 1,393 European males with no underground exposure. The frequency of pulmonary carcinoma was as follows: 1,393 European males, no underground work, 0.93 per cent; 1,679 European miners, no silicosis, 0.71 per cent, and 1,438 European miners with silicosis, 070 per cent. Theoretically, silica should be less likely to initiate a malignant proliferation of epithelium than the tubercle bacillus. The latter not infrequently does cause meta plasia of bronchial epithelium and sometimes carcinoma eventually results. In uncomplicated silicosis, however, there is no effect on the epithelial elements that give rise to cancer. The silica stimulates only the fibroblast or connective tissue cell. If anything there should be an excess of pulmonary sarcomas, but these have not been reported.. In spite of the occasional coexistence of silicosis and primary carcinoma of the lung indicated by published 2S.Vorwald, A. J., and Karr. T. W.: Pneumoconiatia and Pulmonary Carcinoma, Am. J. Path, 14: 49-57 (Jan.) 1938. happen to be involved in the primary fibrosis. Their intrusion into the area of scar formation is easily under stood on reference to Miller's " models of the terminal branches of the bronchial tree. His diagrams show that the terminal air spaces of different brotichial systems are packed together in such a manner that a single section will contain alveoli given off from widely separated bronchi. Many writers have described this condition as bronchiectasis, but emphysema would seem to be a more apt term as the larger bronchi and bronchioles are never involved. The scar tissue of asbestosis is in no way peculiar. Unlike that of silicosis, it fails to show a characteristic hyaline swelling of the collagenous fibers. Its arrange ment is usually, diffuse rather than nodular, although occasional cases such as those reported by Lynch and Smith may present a few nodules. Their presence suggests that there may have been an unrecognized contamination of the inhaled dust with free silica. Because the fibers are not transported, the asbestosis bodies which develop from them will be found very I f" l lo i 26. Saupa, E-: Bemerliungen tar Beurteilung der Silikotc alt tnt- tdudigungtpBicbtiae Beruiikranklieit, Klin. Wchnecbr. 9:1352-1356 (July 19) 1930, 27. Campbell, J. A.: Cancer of Skin and Increite in Incidence of Primary Tumort of Lung in Mice Expoted to Duat Obtained from Tarred Roadt, Brit. J. Exper. Path. 16 1 287-294 (Oct.) 1934. 28. Miner, W. 1936. The Long, Baltimore, Charlet C. Thomat. Publiihcr, 29. Lynch. K. M and Smith, W. A.: Pulmonary Aabeatoti*: IL Report of Cite. Am. Rev. Tubete. 23 ( 643-660 (June) 193l|^J j !* J! 1, !1 * | , J i r. 544 PNE UMOCONIOSIS--GARDNER Joca. A. M. A. Fan. 17, 1940 largely within the scar tissue around bronchioles and the air spaces which they supply. But, as Gloyne 10 has pointed out, commercial asbestos usually contains particles of various contaminating minerals. Physio logic mechanisms within the lung are responsible for the sorting out and removal of much of this particulate matter to the pulmonary framework and lymph nodes. There it sets up a nonspecific pneumoconiosis the color and intensity of which depend on the quantity and character of the contaminant. After the development of parenchymatous fibrosis the particulate matter is not removed so readily. Its retention in the patches of reaction due to the asbestos is responsible for the pig mentation seen in advanced cases of asbestosis. Gross Appearance.--These observations make it easier to appreciate the variable gross picture in asbes tosis. The obvious changes consist of patches or strands of dense scar, which are irregular in size, shape and distribution. In advanced cases they are gray or black and included in all of them are thin-walled, dilated air spaces that vary from a few millimeters to a centimeter or more in diameter. Fibrous pleurisy plus a variable amount of pigmentation in the walls of the pulmonary arteries and interlobular septums com plete the grosser changes. More careful inspection, perhaps with the aid of a magnifying glass, demonstrates numerous minute, ill defined patches of fibrosis widely scattered throughout the parenchyma. If they happen to be sufficiently pig mented by minerals other than -asbestos, such foci will stand out sharply like those illustrated in color in Gloyne's * article, but only one of the twenty-eight cases in my collection even approximates this picture. The borders of these lesions invariably lack the sharp definition- of the silicotic nodule. Here and there the plane of section will cut one of these areas in such a manner that the thick-walled bronchiole with its periph eral fan of fibrosis is clearly recognizable. The lens demonstrates the presence of dilated air spaces within each fibrous area if these are not already large enough to be seen with the naked eye. Elsewhere the air spaces will be visible, but their walls are much less prominent. The patches of fine fibrosis, scattered throughout the lung, are not sufficiently large or dense to be palpated individually, but they increase the general consistency of the organ and limit its crepitation. It is now felt that the fine, diffuse fibrosis with emphysematous dilatation of included air spaces constitutes the characteristic feature of asbestosis. Whether the grosser patches of scar tissue represent merely an intensification of the same process in local ized areas or whether they are due to reaction to dust in the scars of healed infection is not altogether clear. Sometimes they occur as a thin zone beneath and paralleling the pleura, an arrangement hardly sugges tive of infection; at others, more localized patches of scar simulate old foci of infection. The chronic pleurisy is probably not a reliable index of infection, as it seems to occur whenever subpleural air spaces are involved. The thickening of blood vessels and inter lobular septums are variable accompaniments due to accidental contaminants in the inhaled dust. The same is true of reaction in the tracheobronchial nodes. Roentgenograms.--Compared with the microscopic appearances, the roentgenographic shadows of early or even moderately advanced asbestosis are surprisingly 304 Gtaynt, S. R.: Mori'id Anatomy and Histology of A*beto$is, Tubercle 14*445*451 (July), 493-497 (Aug.), 550*55* (Sept.) 1933* slight. A faint haziness throughout the lower lung fields together with more or less evidence of chronic pleurisy are the only unusual features of these cases. Pleural manifestations may be limited to visualization of the transverse fissure of the right lung. There is also more or less exaggeration of the linear markings, but the specificity of this reaction is questionable. As shown by Gardner, Durban, Brumfiel and Sampson,,e in cement workers the frequency of such exaggeration tends to increase more with age than with dust expo sure. Dreesen, DallaValle, Edwards, Miller ar.d Sayers51 concurred but found more of this type ot reaction in old asbestos operators than in persons not exposed to dust and less than in those of the same age exposed to kaolin diist. As suggested in the section on pathology, linear exaggeration is probably an accidental accompaniment of asbestosis and in my opinion should not be considered as an index of early reaction to the fibrous silicates. In far advanced cases there is a heavier diffuse shadow throughout the lung fields, whose appearance has been compared to that of ground glass. Its uni formly fine granular texture is undoubtedly due to the, ~ superimposed shadows of the small patches of fibrosis in the parenchyma alternating with patches of radiotranslucent patent air spaces. The very advanced case may show in addition many small flecklike shadows on the generally hazy background. The shadows never present the sharp definition of silicotic nodulation. The so-called porcupine heart, said to characterize advanced asbestosis, is manifested by heavy linear shadows that radiate into the lung fields from the surface of the . heart. They may be cast by pleuropericardial adhesions.,; -o Clinical Symptoms.--The symptoms most comnionhy^ reported are an irritative cough and dyspnea; some would also include weakness and chest pains. A dusky color suggesting cyanosis, clubbed fingers and blood streaked sputum are symptoms of advanced disease whose frequency apparently varies in different loca tions. Dreesen and his associates*1 find that cough and dyspnea are by far the most common symptoms and that their frequency increases with the intensity of change visualized in the roentgenogram. Of the patients with far advanced cases 82 per cent had both; of those with moderately advanced cases 72 per cent complained of cough and 68 per cent were short of breath. Since the dyspnea must be due largely to asso ciated emphysema, it is quite conceivable that this symptom should appear early and explain the incidence of dyspnea in 33 per cent of persons whose films showed only second degree linear exaggeration. These observers discovered no greater frequency of cardiac involvement than in industrial groups in' general. Others have reached the opposite conclusion, but here again allowances must be made for the source of their material. Theoretically there would seem to be greater reason to suspect cardiac involvement in cases of simple asbestosis than in simple silicosis. Further study is Jneeded to elucidate this point. JMerewether,lT who gave a classic description of this __ | disease, reports that a minimum of seven years' and | <~ } more commonly eleven years' exposure to high concen- { I trations of asbestos dust was necessary to produce a j 0 J serious degree of reaction in the English plants. In loi this country Dreesen and his associates11 found the j a j ---------- --------------- j JQ J 31. Preesen, \V. C.; DallaValle, J. M.: Edwards, T. I.; Miller. T. W.. | and Sayers, R. R,: A Study of Asbestosis in the Asbestos Textile i Industry. U. S. Pub. Health Bull. 241, 1938. 1 I ; > GG Ib 11 b VoLftfi 114 Xcirou 7 PNEUMOCONIOSIS--GARDNER 545 minimum- duration somewhere between five and nine, charged group. The figure for the entire group of years, depending on the character and concentration of employed and discharged subjects cannot be computed die dust inhaled. At this time 27 per cent of exposed as so many of the latter have not been traced. McPhee- workers were involved, and among those with more ters,** among 210 employees front the same districts, than fifteen years of employment die percentage rose found ah incidence of active tuberculosis of 2.8 pefcrr . ; to 60. cent. In Pennsylvania, Fulton, Dooly, Matthews antfcTj j The question of progression after cessation of expo Houtz,T discovered two cases of healed tuberculosis -- sure has had various answers. Merewether11 and among fourteen persons with asbestosis. In "' Ellnianboth believe that asbestosis invariably pro Lanza14 summarized all the available evidence and^--; ` gresses to a fatal termination once enough fiber has failed to find convincing evidence of a great excess been entrapped in the lungs. The former reports one tuberculosis. -JiJr, : .. case in which a mattress maker died eight years after The autopsy statistics are more suggestive. Egbert . ceasing an employment of four years and five months. reviewed the cases reported up to 1935 and found tha > An autopsy revealed far advanced asbestosis. but unfor- six out of twenty-eight showed complicating tuber*- . . tunately there had been no films to indicate the extent of culosis. Merewether11 reports an incidence of 35.&r ` the progression. Mills*3 reported a case in which a per cent in forty-two fatal English cases. Dreesen ana*^ ' ., man died of congestive heart failure approximately his associates 31 include autopsy reports in three case>" thirty-two years after an intermittent exposure of with no tuberculous complications. My own series*.- three years. I was privileged to study sections from which includes twenty-eight specimens, most of whicljr^ this patient, but if there had been any progression it have been previously reported elsewhere, contains nindT" _ 1 - had not involved much of the lungs. There were a cases of active chronic tuberculosis. While thes^j few small patches of pulmonary fibrosis containing rare autopsies reveal a high incidence of such infectionjpJ" -- atypical asbestosis bodies. Lanza34 is of the opinion their number is too small to compensate for the factoff^. that "it is by no means certain that asbestosis pro of selection. The data from the surveys probably con^g gresses as does silicosis'after withdrawal from dust exposure.'' In experimental asbestosis of guinea pigs the pulmonary reaction retrogresses after removal from the dust rooms. On the basis of mechanical injury there should be no progression, for the rounded sur faces of the asbestosis body would produce less trauma stitute a more reliable index. In experimental animals asbestos dust3* has nothing like the effect of free silica on associated infection. Like gypsum, iron oxide and other nonsiliceous min erals, asbestos may cause tuberculous infection to progress for a time, but it subsequently heals with a than the rough ends of the freshly inhaled fibers. Diagnosis depends on a history of adequate exposure, evidence. of characteristic roentgenograpliic changes and the clinical picture. Asbestosis bodies- in the sputum are confirmatory but alone they do not indicate disease. 'Any one may inhale a few asbestos fibers, but their number is too-small to be significant. In routine examination of sections of the lung I have discovered, occasional asbestosis bodies in a dozen or more cases in which no history of exposure to this dust could be obtained. Susceptibility to pulmonary infection in asbestosis is not nearly as well defined as in the case of silicosis. English writers like Merewether,17 Ellman31 ` and Gloyiie 30 are impressed by the high incidence of tuber culosis among the disabled patients and those who died. marked tendency to scar formation. The fibrosis from the infection then retains excessive amounts of inhaled asbestos and unusually large patches of scar develop, in the pulmonary parenchyma. The cause of death in the remaining cases has been certified as nontulyerctilous pneumonia, myocarditis, pul monary cancer and a miscellany of other conditions. Tuberculosis may be an unusually frequent cause of death in certain groups of asbestos workers, but at present it seems more probable that nonspecific hygienic factors and general living conditions are responsible. The actual frequencies of nontuberculous infections arid primary cancer of the lungs are unknown. One must not be misled by a comparatively small number of postmortem reports. 7 Church Street. American statistics based on surveys of employees in different plants, on the other hand, show relatively bole tuberculosis. Dreesen and his associates31 reported only two cases of active infection among 541 persons exposed in the asbestos fabricating plants of North Carolina. However, some 150 employees had been discharged fifteen months previously. Of the latter, seventy-one were examined by Shull,*1 who 36. McPbeetcr*, S. B.: A Sorter of a Group of Employee* Expaed to A*bc*to* Dutt.J. Induti. Hyf. & Toxicol. 181229-239 (April) 1936. 37. Fulton, \v. B-; Dooly. Allan; Matthew*. J. A., and Houtx, R. L.: The Nature and the Amount of Do*t Encountered in A*bc*to* Fabricating Plant* on the Health of a Group of Worker*, Commonwealth of Pennsyl vania. Department of Labor and Industry, Harritburg, (pedal bulletin 42, 1935. 38. Egbert, D. S-: Pulmonary Atbettoaia, An- Rev. Tuberc, 31125-34 (Jan.) 1935. 39. Gardner. L. U-, and Cummings, D. E.: Studies on Experimental Pneumoconiosis;- VI. Asbestoais, J. Indust. Hyg. 13i'65-81 (Feb.) 1931. reported eight cases of tuberculosis, only two of which Effect of Flying on the Ear.--Flying ha* no significant were active at the time. In the entire group "the degree effect on the external ear, but the middle and inner c.ir are the of infiltration was only slight to moderately advanced, source of a great amount of difficulty. The magnitude of the and one or both upper lobes were involved." He found ear problem in aviation may be judged from the fact that pilots that thirty-five of the patients had moderately advanced suffer more frequently from occupational disturbances of this asbestosis, of whom two subsequently died or were organ than from all other occupational diseases combined and dying of tuberculosis, twenty had far advanced asbes that it is the most frequent cause of discomfort among pas tosis with two more cases of tuberculosis. make a total incidence of 72 per cent This would for the dis-* sengers on commercial air lines. The conditions 33mas3oc4setn3ta5fafendct dtehseceenat,r are changes of atmospheric noise, and possibly vibration. of flight which pressure during At the present 0007108 I - I1 \ \ 1 I 1 32- Blman. Philip: Pulmonary A*bto*: It* Clinicri Radiological and Pathological Feature* and Automated Riik of Tuberculoui Infection, } JnduH. Hyi, 131 165-182 (July) 1923. 33. Mill*. R. G.: Pulmonary Asbetiou*: Report of Cate, Minnetota Med. 13:495-499 (July) 1930. time the former is increasing in importance as a result of the increased climbing ability of modern aircraft, while the two latter conditions are decreasing in importance as a result of recent advances in aircraft ` design.--Armstrong. Harry G.: I | CQ I 34. Lama. A. J.i Asbettoii., J. A. M. A. 10: 368 369 (Fek 1) 1936. Principles and Practice of Aviation Medicinej-Baltimorfc Wil*^ 35. Shull, J. R.: Atbe*to*i: A Roentitenopraphie Review of Seventy* One Caiet, Radiology 27 1 279-292 (Stpt) 1936. liams &: Wilkins Company, 1939. (j[j I D | I I