Document GKjJKvJZL31wKDqRpOq70JzjY

State of the Art Silicosis'1 2 MORTON ZISKIND, ROBERT N. JONES, and HANS WEILL j i Contents Miston Geology and Occup ' tionai Sources Characterization of Exposure Pathogenesis Pathology Clinical Features Diagnosis I ung Fun< rion Treatmen: Prevention History The eff eij, of iIiicj-.i.s, the chronic fibrosing dis ease of tht iungs produced bv prolonged and ex tensive exposure to free crvstalline silica, have bet n recognized fo' centuries. Pulmonary dis ease produced be dost is mentioned by Agricola in his Trc-nisr ori Mining (1556) and is de scribed in stonectioers bv van Diemerbroeck (1672) and Ramazzmi (1713. (1). The physical evidence of previous occupational exposure to sources of Iree silica abound in old mines, aban doned quarries, and ancient flint tools and weapons (2> The disease can be acquired dur ing direct oneration- with siliceous materials or in mineral xtraction in which the free silica is 1 From the Pulmonary Disease Section, Depart ment of Medicine Tiuane University School ot Med icine New Orleans, L. 2 Supported in pa; be USPHS Grant 1 12 HE 05829-6, National Institutes oi Health; Grant OH 00387-03, National lri-niuie (Oi Occupaiional Safeiv anc Health and N'HLI SCOR Grant P 17 HL 15092-02 8 Request; tot reprints should be addressed to Dr Morton Ziskuid 170( Perdido Street, New1 Orleans, La. 70112 contained in the residual rock. The exposure in such operations produces contact with high concentrations of dangerous fibrogenic material. Technologic advances that have supplied power ful sources of energy to industry have greatly in creased the dust exposure of the worker. The pneumoconioses became more frequent and de veloped more rapidly after the introduction of steam machinery into factories at the turn of the nineteenth centurv Zenker (1866) gave the gen eral name pneumoconiosis to the group. Kuss- maul (1866) demonstrated silica within the lungs. The specific name silicosis (Latin, silex, flint) was applied by Visconti (1870) (3). In tensive mining using pneumatic drills and mod ern energy source; made mining even more dan gerous at the turn of this century. The gold mines in South Africa were opened in 1886 and clinical disea&e and pathology were described in this location in 1902 (3). Haldane (1902, 1914) stated that silica created the dust hazards for tin miners, and Collis (1915) proposed the the ory that crystalline silica was the cause of most serious lung disease and predisposition to tuber culosis related to dust exposure (1). Increasing imprest in industrial hygiene lpd to more inten sive study oi traditional trades carrying a dan gerous free silica exposure, such as work in pot teries. quarries, brick yards, and foundries. The frequency of the disease in metal grinders was known in the earh nineteenth century. The high risk of work with granite was recognized almost a centurv later (4i Rapidly developing disease ("acute silicosis") was reported in scouring pow der workers in 1929 after a short, intense expo sure to high concentrations of free silica (5). The same course of illness has been described in runnelers (6) and sandblasters (7). AMERICAN REVIEW Or- RESPIRATORY DISEASE. VOLUME 1J3, 197b 643 jAsL j 644 ZISKIND. JONES. AND WEILL The great increase in frequency of pneumo coniosis in coal miners and associated workers in this century led to special studies that have ad vanced our understanding of the pathogenesis, pathology, roentgenographic appearances, and progression of silicosis (8). Epidemiologic stud ies of involved workers have thrown light on the determinants of group disease (9). The relation of dust exposure to tissue reaction as visualized on chest roentgenograms and alterations in pulmonarv function is under continuing study. Ex periences with the coal workers has established the importance of the concept of mixed dust ex posure and has made it possible to some degree to distinguish changes produced by prolonged coal dust exposure from those created by free silica (ID). This concept has been of great im portance in deciding the part that silica plays in the development of diffuse pulmonary fibrosis and pleural changes. It appears that admixed free silica accounts for the pulmonary disease produced by bentonite and montmorillonite. To a lesser degree, free silica may produce disease in workers exposed to talc and kaolin. In those instances where the workers are exposed to in dustrial combinations of asbestos and sand, vari able degrees of nodular silicosis have developed. Mixing of substances containing free silica with other dusts or chemical substances has main tained the silica hazard in industry. Understand ing of chemical changes has demonstrated that certain substances become increasingly danger ous in the course of industrial processes. The heating of diatoinaceous earth produces high concentrations o cristobalitc and uidymitc which are forms of crvstalline silica more danger ous than the commonlv encountered quartz (11). In the course of industrial development through out the world, problems of production have led to the revival of dangerous industrial pro cesses. Abrasives for the cleaning of metal surfaces before painting arc in constant de mand in construction and shipbuilding. In older industrial regions, the use of sandblasting for such purposes has been forbidden by law United Kingdom, 1949, and European Econom ic Community, 1966). Sand as an abrasive has been extensively used in the United States in shipbuilding operations and in preparation and maintenance of oil rigs for offshore drilling since the termination of World War II. This has produced a resurgence of accelerated silicosis in sandblasters, leading to a large number of in juries and legal claims. Health and financial costs have therefore increased and have engen dered a great need for modem protective devices and preventive work practices. Protective mea sures adopted in the past have almost eliminated clinical silicosis in quaWv workers (12) and met al miners (13). At this time, the use of metai grit and coal ash residue promises to eliminate silicosis in abrasive blasters. The early literature on silicosis is relatively limited. Important accounts were supplied bv writers working for official institutions in South Africa (14), Australia (15), and Great Britain (16). In the United States, the earliest reports came from the U. S. Public Health Service (17). A pioneer monograph on roentgenology in pneumoconiosis was written by Americans (18). The early situation in the roentgenography of silicosis is described with personal reminiscences by Cole in a valuable and entertaining book (19). Descriptions of the pathologic fea tures of silicosis are encountered in the works of Gardner (20), Gloyne (21), and the South Afri cans, Simson and Strachan (22). The earliest works on general studies of miners' diseases are given in varying detail by Rosen (23) and Meiklejohn (24). The enlarging literature contains valuable accounts of national experiences with silicosis. A French monograph (25) and a large Swedish text (26) described the situation before I960. In the encyclopedic volumes on occupa tional health and safety published by the Inter national Labour Organization (27), there are substantial sections devoted to silicosis. Valuable material will be found in the latest edition of Hamilton and Hardy's textbook (11). The ex perience of the U. S. Public Health Service is brought up to date in the recent criteria docu ment on crystalline silica published bv the Na tional Institute of Occupational Safety and Health (28). There is a large section on silicosis that includes historic data in Hunter's The Dis eases of Occupation (2). Modern clinical ac counts of silicosis are found in 2 excellent recent books by Parkes (29) and Morgan and Seaton (30). In Baum's textbook (31), Kleinerman writes a full account of silicosis and the other pneumoconioses. A monograph on experimen tal pneumoconiosis includes extensive material on silicosis (1). The proceedings of the Inter national Pneumoconiosis Conference (32) and of the International Symposia on Inhaled Par ticles and Vapors (33) review current epidemi ologic. experimental, and environmental work. Geology and Occupational Sources Most of the earth's crust consists of compounds SILICOSIS 645 of silicon .uid oxvgt u. The plice of silicon in the IrK.igaim world is similar 10 [hai ol carbon in methods in enclosed spaces while handling sub stances containing high concentrations of crys tht organu sphere The compound that is re talline free silica is demonstrated in tunneling sponsible for the development of silicosis is sili and in sandblasting (35, 36). Rapid develop con dioxide which occurs in nature in 3 differ ment of complicated silicosis was vividly illus ent crystalline forms: quart?.. with hexagonal trated at Gaulev Bridge, W. Va., in 1931 (6). crystals- rris-obalite with cubic crystals: and tri- Unprotected tunnelers encountered a vein of dyinite. wit; hexagonal crystals. Quartz, a hard. quartz and dec eloped fatal silicosis after short colorless substance, is the most common of all cxposuies, in some cases less than one year. 1 he minerals am. is a constituent ol many rocks, such same pattern of rapidly developing disease oc- as granite and sandstone. The structure of quartz i urred in abrasive powder workers, who also is described is tonsis'ing of SiO^ tetrahedra, wdth worked in enclosed spaces with no respiratory each oxvger atom se rving as the corner of 2 of protection the tetrahedra. Jo break a civstal of quartz, it Free silica is widely used in industry, but the is necessary to dividt some silicon-oxygen bonds. T he strut lure of quartz accounts for the hard dust risk may be unsuspected because of its ad mixture in rock structure or clay. Combination ness of the mineral (H4). of free silica with other minerals is a common 1 he uncombined :orms of silicon dioxide are industrial practice: The silica is often added to called, collectively, iree silica" to distinguish asbestos in asbestos-cement mixtures for the pro them from silicates, which contain cations. The duction ol pipe, tile, and roofing, and to cement silicates are found ii chains and in more com and concrete for use in heaw construction. plex structures. The following list of principal industrial The ubiquitous ptesence of silicon dioxide in sources of free silica is modified from Parkes the earth s oust is the prime factor responsible (29): for rlie frequent contact of workers of various (1) Mining, quarrying, and tunneling. The occupations with the substance The silica-rich mining of gold, tin, copper, and mica produces rock ui iniiit j al mac be directly quarried for a dust containing high concentrations of free sil purposes ol . onstruci ion or mav be the matrix ica. Sandstone is a rich source of quartz that in which a desired material is embedded Re mav be encountered in the development of sidual rock is sometimes used lor industrial pur gold mines Quarrying of quartz leads to expo poses. notably in construction: but when the sure to dust containing 10 to 30 per cent of free special properties of free silica are needed for silica. The quartz content of dust from quar abrasives, relatively pure forms of the crystalline ried slate may approach 20 to 30 per cent. Tun material arc used. Crvpto-crvsrallinc flints have neling through sione containing quartz or dig been used since pre-recorded history, and with ging graves in sandstone has been associated with other materials containing silicon dioxide in the production of silicosis. high concentrations are used in those industries (2) Stonecutting, dressing, polishing, and in which hard, heat-resistant materials are re cleaning monumental masonry. In this work, the quired for production of pottery and porcelain stones used, sandstone and granite, contain high and in casting metals Crystalline silica mav be present in lesser concentrations (up to 10 to 24 concentrations of quartz and are dangerous be cause of both the silica coinciu and rile difficulty per cent) when silicates such as fuller's earth and in protecting the worker, who is in close contact bentonite are mined The noncrystalline (or with the material and frequently removes his amorphous) forms of silica are regarded as hav- protective devices to inspect his work. Pneumat *ng little or no fibropenic properties but may ic hand tools are used for cutting and smoothing; acquire these if heated or calcined abrasive blasting for lettering and decoration The histon of industrial development shows increases the risk of the procedure. how the silica hazard has increased with the ap (T) Abrasives and abrasive blasting. Sand plication of new and more powerful sources of stone grindstones are now rarely used, but sand mechanical energy to he earths crust In min- paper and scouring powders still contain flints ng and quarrying, the introduction of pneu- and quartz The use of abrasive soaps and scour dc drills and blasting increased production ing powders was recently discontinued in the produced larger dust clouds that contained United Kingdom. The risk from abrasive blast concentrations o! respirable particles (< ing is greatest when sand propelled by com in diameter) The danger of using such pressed air is used This has been largely re ND WEILL scope to examine small particles of the materia However, shot bias'"1* ot sand MP)n metal castings treat' s 'lust conuinfaffpt concentra tions of respirable tree SlMc. ! i-ri Glass manufacture, limited use of sand ill slurries to grind glass has continued in the operations of small companies. Foundry work. The free silica used in (37). In analysis of finely divided material roentgenographic diffraction may be used if tin sample contains more than 200 ,ug of free silica but the error of current methods is about 30 per cent (38). In the absence of other silicon com pounds (silicates or amorphous silica), a wet chemical method can be used in which hydro foundrv work contaminates the atmosphere be cause of the development of molds containing chloric and hydrofluoric acids separate the free silica, which is read by colorimetry (39), Infra sand and clay. The work is carried out at high red spectrophotometry is also used in analysis of temperatures and there is some conversion of dust containing free silica (40). quart/ to cristobalite. There is a trend toward Measurement of the degree of exposure to sand substitutes that do not contain quartz; oliv respirable free silica is necessary to determine ine is said to be in general use in Sweden. The the risk of disease within the industrial environ widespread use of sand molds and the use of ment. Standards have been published through blasting, hammering, and chiseling create a dus the years that were originally based on a unit of ty environment containing iron oxide and quartz one million respirable particles in a cubic foot and lead to a form of pneumoconiosis to which of air (mppcf). Current standards are usually silica probably makes the most important con expressed in milligrams of respirable dust per tribution. cubic meter. The current threshold limit value (6) Pottery, porcelain, and lining bricks. The for respirable dust containing free silica (Amer combination of materials containing free silica ican Conference of Government Industrial Hy- in concentrations varying from 2 per cent to 30 per tem and the high temperatures used creates 300 gicnists, 1973) is (I) -------------------- in mppcf, % quartz + 10 a serious silicosis risk. (7) Boiler scaling. High energy sources are or (2) 10 % quartz in mg per m3. This calcu- used in this work creating mixed dust clouds lated threshold limit value is divided bv 2 if the with variable concentrations of respirable quartz dust contains cristobalite or tridymite instead of particles. quartz. For respirable nuisance particulates con (H) Vitreous enameling. All such occupations taining less than 1 per rent of quartz, the thres produce contact with significant amounts of free hold limit value is 30 mppcf or 10 mg per m3. A silica. Because of the use of high temperatures new standard for silica exposure has recently and pneumatic air jets or other high pressure been proposed (28). techniques, a dusty environment is produced A number of methods have been used to mea that will expose workers to excessive concentra sure the concentration of dust in the atmosphere. tions of free silica. These include (/) settlement bv gravity or cen Characterization of Exposure trifugation, (2) filtration, (3) impingement, (4) electric precipitation, and (5) thermal pre I he development of silicosis depends on the in cipitation. halation of respirable free silica particles < 10 The method of impingement was modified urn in diameter. The size range for maximal al successively to scivc as a field method for sampl veolar deposition is 1 to 3 urn. Free silica con ing industrial dusts. An earlv technique was the centrations vary greatly in materials that enter konimeter method, in which the dust particles into industrial processes. Concentrations usually were sucked onto a plate covered with a thin film exceed 60 per cent in sand, but this material is of petroleum. The number of particles collected not hazardous under ordinary conditions be within a given time was calculated by magnifica cause the particles are coarse and unrespirable. tion of a microscopic grid. Readings of this in Where powerful desert winds whip up sand strument were high because fiagiiientation ot storms, clinical silicosis does not occur; definite particles by impingement exaggerated the rela hyaline nodules have not been demonstrated in tive dust hazard. A related instrument, the im- the lungs of inhabitants of the desert. pinger, was originally described in 1932 (41): The silica content of natural substances can more recently, it has been modified by Green- be studied in several wavs. The traditional meth burg and Smith to produce a practical field in od in petrology is to use the polarizing micro strument known as the midget impinger, in SILICOSIS 647 wim h panicles were "ntrapped bv high velocity impiiigemen and collected in water and alco hol In the nortable midget impinger. panicles tnipnge ai .. velocity of 7b per sec. and the air flow for sampling is 1.1 at ft per min The in strument can be opei ated b\ hand or bs electric pump, with the panicles being collected in a liquid solume of 10 ml The midge: impinger reduced the risls of scattering large panicles or the loss of (.articles alter impingement, but ag gregated panicles th.u broke up on contact with the fluid wntun the collection chamber increased the dust count. 1 tie instrument that is in general use m field opeuitioits rodas is the personal gravimetric dust sampler, f fit sample, is composed oi a cvtiorie assemble and filter holder containing a preweigheci tniliipore fiber that is attached to a bat ten powered puntp. in the Mine Safety Appli ance sample' the pump draws air through the assemble at a flow rate of J.7 iiter per min. Noilrespirable particles : 10 Mm are discarded and the smaller particles adhere io the filter (42). Tht total weight of dust on the filter is estab lished and tiie weigh of the sample is obtained hv subtraction. Tht dust is analvzed be one n( t lie met hods previously described Pathogenesis Events in the pathogenesis o! silicosis include ;y i inhalation ol silica particles, then penetra tion t,;> tht lung periohere. and their retention; (21 ingestion ol the particles by macrophages; (T death of 'he macrophages: (4) release of the contents of tlie killed cells, including silica par ticles. ( v mgestton of silica by other macro phages and iheir deadis; (6> gradual accumula tion of other cells; : ~) production of collagen; (St hvalmization; and (9) (possibly;, compli cation. Particles deposited in alveoli are readily in gested b\ mac rophagrs, the process resulting in treason ol a phagosome from tnvaginated cell membranes Silica particles at first lie within the phagosomes, which receive enzvmes from the lvsosomes. VViiitin hours, however, the phagosome ruptures anti silica particles can be demonstrat ed iving fre- in the cytoplasm (43). The ivsosomai en/vnn s. discharged into the cvioplasm in actuated iorms. are probably responsible for the rapid death >f the macrophage and extracellu lar loss ol its content' including the particulate silica (44; More macrophages accumulate in the area, ingest the silica, arte; are killed. This cytotoxic effect of silua is a necessary step in the production of silicotic fibrosis. For a variety of mineral dusts, good correlation between ma crophage toxic it v and fibrogenicitv has been demonstrated (45. 461. The relative east and speed with which one mas expose macrophages to dust and detect phago-omal rupture and cell death have led to a number of studies of the relative cytotoxicity of sat ions dusts. This assay system circumvents problems of particle penetration and reten tion in studies of relative pathogenicity and al lows studies relating particle size and composi tion to actual cell toxicity (47). A number of substances are ingested by macrophages and lie undigested in phagosomes but fail to alter per meability of tftt phagosomal membrane. Macrophages may become "choked" with such dusts and vet retain mobility as well as structural integrity. Carborundum and diamond dust fail to show macrophage toxicitv, although they are angular and sharp (48). These experiments, in fact, demonstrate on a cellular level the basis of earlier animal studies that disposed of the "angu larity theory" of siltcogenesis. Stishovite, a rare form of crystalline free silica, also accumulates harmlessly in macrophages and fails to produce fibrosis (49). This material is octahedral; only the tetrahedral forms of silicon dioxide possess evtotoxic and fibrogenic properties. Coesite is another high temperature, high pressure form of silica Quartz is more soluble than coesite, but the 2 minerals possess equal fibrogenic activity (50). In other experiments, differing quartz spe cimens with similar particle sizes and solubili ties have shown significant differences in fibro genicitv (51). The foregoing have led to the rejection of the solubility theory of silicogenesis and to increased interest in stereochemical hy potheses. The importance of silanol groups on the surfaces of silica particles has recently been emphasized (51). The formation of hydrogenbonded complexes between silica particles and active groups of the phagosomal membranes (such as quaternary and phosphate ester groups of phospholipids) may be the mechanism pro ducing rupture of the phagosome (52). The hy drogen donor hypothesis has another attractive feature, namely, that most of the compounds that protect against experimental silicosis be have as hvdrogen acceptors (53, 54). Experi ments relating the particle size of colloidal silica to its activity in rupturing erythrocyte mem branes lend support to a stereochemical rather than a simple "energy-transfer" explanation for membrane toxicity. The larger particle sizes of 8 ZISKIND, JONES, AND WEILL colloidal silica are more hemolytic; 3 pm par ticles lack hemolvtic effect and, in fact, protect against the effects of subsequent exposure to the larger particle sizes even after repeated wash ing of the treated ervthrocvtes. The implication is that the smaller particles can become firmly attached to the cell membrane but lack sufficient surface area to effect membrane rupture (54). Further support for a stereochemical hypothesis ..omes from the fact that stishnvire, lacking cy iotoxic or fibrogenic properties, does possess sur face silanol groups (511. Apparently, the octa hedral configuration of stishovite prevents the orientation of silanol groups that produces mem brane disruption. The proposed membrane tox icity of particulate silica is thus more geometric than energetic; however this does not require that the silica be in crystalline form (55, 56). Other recent work has examined the induc tion of fibrosis by products of dusted macroph ages. In these experiments, macrophages are har vested from dusted animals or are exposed to particulate silica in vitro. The cells mav then be Ksed bv ultrasound and separated into fractions rhat are subsequently injected subcutaneously into animals of the same species to assav for fibrogenicitv. Control experiments have shown that residues from lysed nondusted macrophages pro duce little if any fibrosis. To exclude a direct effect of silica the mineral was added to the resi due of lysed hut undusted macrophages, and this mixture also produced little fibrosis. Using these methods, Heppleston and Styles (45) found a fibrinogenic factor in the supernate of a centri fuged suspension Of dusted lysed macrophages. 1 hev considered this factor soluble. Kilroe-Smith and associates (57) used similar experimental methods but much higher speeds of centrifuga tion. They found the fibrinogenic activity in the residue, not the supernate This fibrogenic fac tor was not a lipid, because it was not extracted bv methanol-chloroform, the factor was also re sistant to treatment with acetic trichloracetic acid. Further work on macrophages in vitro has demonstrated a toxic basis for the impaired re sistance of silicotic patients to certain infections. Msi obuctenum tuberculosis grows more rapidly in macrophages that are fed sublethal doses of quartz particles, and the bacilli are released more rapidlv into the surrounding medium (58). At this point, it is useful to consider some differences between these experimental models and human silicosis. The models require high silica doses, administered for relatively brief ex posure times, to produce rapid biologic respons es. These are exactly opposite to the usual con ditions leading to human silicosis. Differences in individual exposures, in anatomic and physi ologic factors governing particle retention, in exposures to other noxious agents, and in host responses to retained silica must separately and together be important determinants of which ex posed persons will actually develop disease. Ex perimental models may therefore exclude some mechanisms that ultimately prove to be of con siderable importance in human silicosis. Although these models have provided useful da ta on limited aspects of silicosis and have indi cated promising areas for new research efforts, they have yet to provide an inclusive theory of silicogenesis. Recent work has challenged the ap parent simplicity of explaining fibrogenesis bv a factor released from dusted cells (59). Autoimmunity may be important in several phases of development of silicosis. Interest in immunologic mechanisms is based on several ob servations: (1) silicotics show increased preva lence of autoantibodies (60-63); (2) silicotic lesions contain plasma cells and immune globu lins (64-66); (3) gamma globulins are in creased in the plasma of silicotics (64); (4) there is an increased prevalence of autoim mune diseases in silicosis (67-69); (.5) the pres ence of a collagen disease mav influence the course of the pneumoconiosis (70). Immune mechanisms probably do not participate in the killing of macrophages by silica, or in the induc tion of fibrosis by the residues of the dusted ma crophages. Immune reactions may, however, be responsible for providing a large and continu ing supply of macrophages to the area and may thus occupy a central role in the pathogenesis. Established silicotic nodules (in rats) may be come more active in the presence of remote tuberculous foci (71), and Caplan's observations (70) suggest a similar effect of immune globu lins in man. Another area of possible importance is the role of lipids in silicosis. The initial attack of silica on the phagosomal membrane may in volve hydrogen bonding to lipids. The finding that lipid residues of dusted macrophages lack fibrogenicity does not vitiate the importance of lipids in the intact animal. Lipids may have an arfivp part in macrophage accumulation and may also have passive effects in rendering silica particles less wettable (72). In any case, striking alterations in lipid content (and metabolism) characterize silicotic tissues (73). Pathology 4 hree types of tissue reaction have been distin SILICOSIS 649 guished 74, chroni. in which moderate ex posure exieiuU for a period of 20 to 40 years; accelerated, "ith incieased particle dose for a period of 5 i" 15 vears: and diffuse, in which there is a heavy alveolar deposition of particles for a period o' less thai 5 vears. Chronic reactions are encountered in indus tries m whit I' the proportion of quartz in re spirable dust is less than 30 per cent In such cases the nodules art seen aft< r approximately 20 years of exposure, i hese are usually rounded bui may take oval oi slightly iobufated forms The distribution is uneven, wit ft lesions usually more prominent within the upper lobes, prob ably relating to better clearance of dust from the lung bases Studies of ttostrrioriem material haveshown tfiat pi actually alJ of ihe silica particles visualized wit fun the iungs art 1 to 2 wm in di ameter Careful studies of human and experi mental material have demonstrated that the par ticles can reaefi the supporting tissue of the finer air spaces either through macrophages or less commonly as a result of the movements of the iungs The panicles pass toward the hilar lymph node-, where free silica is concentrated. The death- of macrophages usually leads to the for mation of nodule- corlaming free silica in the fixed interstitial tissue -tear the respiratory bron chiole Here ihe nodules lie in relation to bronchioles and small arteries They are also found near the lymphatics of the small veins. In chronic disease the nodules surround a cen tral hvaline zone that contains a variable amount of dust. This is in turn surrounded by a concen tric zone of cellular connective tissue that con tains no panicles; it is surrounded by a halo of dust containing crystalline silica in a zone of ir regularly dispersed connective tissue, which also contains crystalline silica. It is from the periph eral zone that silica is carried to enlarge the nodules and set up new silicotic nodules. A typi cal hyaline nodule is shown in figure 1. Variations in the lormation of the nodules have been noted. Alveolar wall involvement can lead to denudation of the overlying layer and the formation of a lumpy cellular lesion protuding into the alveoli (figure 2) that resembles bron chiolitis fibrosa obliterans (75). In the simple stage of silicosis, with few nodules larger than 5 mm, the surrounding air spaces are usually not violated. The hyaline material shows some re semblance to amyloid (74). Serum globulins within the hvaline material have been demon strated bv Y'igliani and Pernis (64). Silicosis is often complicated by the formation of massive fibrotic lesions that usually develop within the upper lobes. They are composed of nodules matted together by fibrosis and contain obliterated blood vessels and bronchi. Ischemic slit-like cavities mat be demonstrated, but in the past the most important type of cavitation reported was produced by associated tuberculo sis. In coal miners with rheumatoid arthritis, Caplan (70) noted an increased prevalence of mas sive fibrosis. The larger masses were associated Fig 1 Classical silicotic hvaline nodules associated with adjoining parenchyma] scarring and limited Ivmphoid exudate (Original magnification X 40) 650 Z1SKIND, JONES. AND WEILL Fig 2 Diffuse alveolar wall thickening bv histiocytes with air space encroachment (Original magni fication: x 140). with a crop of round, rapidly developing opaci ties larger than simple silicotic nodules. Cavita tion and calcification in the larger nodules has been described. Pathologic examination has demonstrated that Caplan's nodules contain ne crotic materials surrounded by palisading con nective tissue cells as seen in rheumatoid sub cutaneous nodules. Complicated silicosis is char acterized by distortion of the structure of the lungs with contraction of upper lobes and the development of emphysematous changes in the lower lobes, often with large bullae. Pleural ad herence is common in this form of the disease. The enlarged lymph nodes often contain periph eral layers of calcium producing the fairly char acteristic eggshell appearance. The masses can occupy one-third or more of the upper lobes. The disease has been noted :o cross the interlobar fissure. The amount of dust within the masses is variable. In tuberculosis, occasional caseating granulomas mav be found, but the histologic reactions may be nonspecific. There are numer ous complications of silicosis. Cor pulmonale has been frequently mentioned but is not often con firmed on pathologic examination. Calcified Ivmph nodes, often the result of previous tuber culous infection, have produced the following changes in neighboring structures: the superior vena cava syndrome, esophageal compression, perforation of the bronchial tree with infection and hemorrhage, and paralysis of the phrenic nerve and, less often, the recurrent larvngeal nerve (76). Data concerning the residual ash from silicotic lungs have been published (37, 77). The upper limit of normal content of free silica in human lungs is 0.2 g, whereas in disease, the quantitv of free silica may rise to 15 to 20 g. .YfcCrae showed that in the normal person the average percentage of silica in ash was 14.7 per cent. This rose to the range of 29.4 to 48 per cent in patients with silicosis. The silicon percentage of dry matter was 4.7 in the most severe cases (78). Patients with silicosis usually had at least twice as much free silica in their lungs, in percentages of drv matter, than did normal persons. Others have shown that the lungs of normal persons contain less than 0.12 per cent silica but thar the fibro sis in silicotuberculous patients is excessive for the amount of silica in their lungs (79). The importance of the silica content in relation to fibrosis has been shown bv Rossiter: The amount of visible reaction on the chest roentgenograms was related to the total amount of coal dust, ex cept in those instances in which the percentage of free silica w'as increased (80). The changes that have been described in chronic silicosis are also seen in accelerated sili cosis, but the rate of progression is more rapid and the lesions usually become visible on chest roentgenograms after 4 to 8 years of exposure. Much of the information on this group has been ob'ained from stucbes of sandblasters. In these m< n wc 11 forme d nodules de veloped, but there vta. a tendtntv for nodules to form tit relation to 'he walls of the atveolar spate, instead of near the respirators bronchiole a: the orifice of the acinus fSl The disease leads more frequently to massive fibrosis, and the large opacities are seen more oiten in ;ile middlt and basal portions oi 'he lung' than in chronic dlicosis. Cav itation is as frequtnth the result of atvptcal mycobac terial infection as of human tuberculosis 182). 1st'hemic ca' itarion mas also occur Acute' silicosis t- a rare condition related to exposure n hears ., oncentrations of respirable tree siltta si enclosed spaces with minimal pro tection The disease develops rapidls anti clini cal features appear after an exposure of approx imately ! to 3 seat On autopsy, there is con solidation with maintained lung volume The lungs have a gravi'h white airless appearance with thickening related to diffuse interstitial fi brosis. The nodulation and massive changes of the more chronic foims of silicosis are not grossly demonstrable. Because of termiral pulmonary edema or ex udation. flmd Hows from tht cut surfaces. The disease is usually complicated by mycobacterial or other infections hat produce thickened and adherent pleura. A striking microscopic change is rtie prest nee of acidophilic fluid, containing firit granules and many macrophages, within the alveola! spates figure 3| There is also cu- boidal transformation of the alveolar cells. In terstitial fibrosis is prominent, but silicotic nod tiles are poorly demarcated and small (6). The Hind within these spaces contains lipids and pro teins and gives a strongly positive reaction to periodic Schiff reagent (7). Quartz crystals are present within the lungs and the hilar lymph nodes The cells seen within the alveolar spaces are macrophages, but it is possihle that in the course of the disease tvpe 2 pneumocytes are desquamated into the alveolar spaces as well. The reaction of silica has been elucidated by experimental exposure of laboratory animals. Silica has been introduced into the respiratory tract bv dusting or by direct intratracheal injec tion Subcutaneous, intravenous, and intraperiicmeal routes of administration have been used. Silica has even been placed in the anterior cham ber of the eve. Important studies have been carried out on macrophages exposed to free sili ca in tissue culture media. Lesions produced in animals have been studied for silica content bv the sensitive spectrophotometric colorimetric method in which silicomolvbdate is formed. A number of animal models have been used for these studies Examinations at various inter vals have denionsiraicii the course of silicotic le sions. Typical compact nodules have been pro duced in rats after exposure in dust chambers for periods as long as one year (83). Collagenous nodules have also been produced in chronically dusted monkevs (84) In the hamster, nodulation Fig S .Silico-proteinosis The alveolus is filled with macrophages associated with pigment granules and proteinaceous material The alveolar margins are demarcated bv congested capillaries. m 2ISRIND, JONES. AND WEILL occurs early, is widespread, and is associated with diffuse pulmonarv fibrosis. This is probably related to numerous loci in lvmphoid tissue scat tered throughout the lungs (85V Intratracheal injection of a massive dose of free silica usually produces acute cellular reaction, which fills the dr -.paces and only later leads to the formation of nodules and fibrosis. This reaction is well illus trated in the guinea pig (8fi). The sequence of focal collection of dust cells followed hv the con cemration of fibroblasts leading to definite col lagen nodules has been demonstrated in mon- kevs chronically exposed to small particles of quart/. 3 or less. Under similar conditions, amorphous fused silica dust produced only lim ited fibrosis. The resistance to mvcobacteria of dusted ani mals, often guinea pigs and rats, has been stud ied bv experimental methods. The native resis tance of both species was altered by silica. The disease was produced more readily by virulent organisms and by attenuated strains that ordi narily would not produce infection. Mycobac terium marmum produced progressive disease in guinea pigs after their exposure to silica by both intratracheal injection and dusting tech niques. Clinical Features Silicosis is usually a chronic disease, and the principal symptoms develop late; it is rare for the chest film to become positive before 20 years of exposure. In the past, the average duration of life after first exposure has been approximately 40 years for those whose exposure to free silica was moderate, as in foundrymen. quarrymen, miners, and potters (87). An earlier, more rapid onset of the disease would be an indication of heavier exposure due to unusual circumstances of employment (lack of protection and work in enclosed spaces), or an infectious or immunolog ic complication. The earliest symptoms in chronic cases are cough and expectoration, which can usually be explained by a history of cigarette smoking ex tending back to early youth. The principal symp tom of established silicosis is shortness of breath on effort. This is usually associated with roent genograms showing complicated, rather than simple pneumoconiosis. Significant dyspnea on effort is almost invariably related to massive changes within the lungs, contraction of lobes, or cavitation of infectious or ischemic origin. Distortion of the bronchial tree under these cir cumstances leads to increased cough and expec toration, but these symptoms will be more sc if cavities are present. Hemoptvsis and ci pain due to infection are nor uncomm. Weight loss is a characteristic finding in sii: tuberculosis and other types of infective pm moconioses. Myrnric infections, including ; cardiosis, cryptococcosis, and sporotrichosis, ha complicated this pneumoconiosis. Infections i particularly common when silicosis is accelerate or acute. Respiratory failure is the most important to; sequence of complicated silicosis. Ventilatoi failure may be aggravated by the developmet of pneumothorax, which resists successful trea ment because of the difficulty in obtaining rt expansion of the shrunken, fibrotic lung and it sealing the leak in the poorly retractile tissue. There have been a number of reports dealing with the increased prevalence of scleroderma in pneumoconiosis and silica exposure In our ex perience, autoimmune disease has often been associated with the accelerated type of silicosis seen in sandblasters: About 10 per cent devel oped connective tissue disorders, including scle roderma, rheumatoid arthritis, and systemic lu pus erythematosus. The role of the complicat ing disease is uncertain but is usually associated with more rapid progression of roentgenographic and functional abnormalities. It is in these cases that some response to adrenal corti costeroids may be noted. The evolution of silico sis associated with auto-immune disease can be very rapid, producing marked structural and functional changes within the course of 1 or 2 ycuis. In accelerated silicosis, the major features of the disease are identical to the chronic disease, but the chest roentgenogram usuallv becomes positive within 4 to 8 years of first dust exposure. The over all course of deterioration is rapid and the average exposure to free silica is approxi mately 10 years in fatal cases of sandblasters' silicosis. Mycobacteriosis affects 25 per cent of the workers; half of these infections are due to atypical organisms. In Wisconsin, the common atypical mycobacterium complicating silicosis is Af. mtracellulare (Battev bacillus) (88). This is the organism usually associated with rural res idence In the coastal /cutes, and near the larger cities of the southwest, AT kansasii has been the atypical mycobacterium usually associated with silicosis. Most of the disease described above has been related to high doses of free crystalline silica. Smaller doses of quartz produce a rather mild SILICOSIS 653 disease of long duranon. Thi- raai occur in palitnt' cxpi'M d li minor amounts of quart/ con taminating othe r minerals. s die opt ot- ino'is i- the name applied to a sariant :>( rapid s dcscloning silicosis in which there arc har.K it istic histologic changes, li is the re sult of tieas' exposure to respirable silica dust. Ds'imea on "(foil m s develop svithm 6 months of tost expiourt 1 here is associated weakness and ss-etglit a>ss and in more severe cases, cya nosis and diffuse rai 's. Complication by myco bacterial irilection i- the rule but in one case treated with steroids there was terminal nocardio'is Progressive de'erioration mas be tempor al ih and pa-nails suppressed bv corticosteroids IDeath is due o irurai able hvpoxemia. The pies alenic o nitrobacteria! infections mas be declining for Itromc silicosis but remains high lor the accelerated and acute forms. The roetiigenogiatihu appearance varies from char acteristic ctu uars infiltrates to massive disease, with or without cavitation in which tuberculous elements rnas be difficult to distinguish. In those svici positive spuiurr culcures the rale of spu tum .onsersion is high; but the massive disease and conglomerate lesions will often pi ogress de spite appropriate cheinotherapv (891, A number of investigators indicate that tuber culosis tend- to complicate silicotic disease of long standing and th i it tends to be more severe in the more tapidlv progressive tvpes of the dis ease Can prior silica exposure, insufficient to produce nodulation on the chest roentgenogram, predispose a person to tuberculosis? In persons who have had years of silica exposure and nega tive roentgenograms active tuberculosis may suddenlv appear In some instances, the disease may continue to progress and produce massive lesions without visible associated nodular foci Macrophages are of undoubted importance in immunity to mycobacaerial infections; it is preclselv these c'Tls that demonstrate exquisite sus ceptibility to he toxic effect of particulate silica. Watkins-Pitchford (90) found an association be tween work as a gold miner for 8 to 5 vears and the -tubsequeut development of tuberculosis, even though silicosis was not demonstrated on the c iiest roentgenograms. Thn- potentially imporiam observation nas not been confirmed The progressive and massive manges produced bv irvcobanenal infection in silicosis have not been described tor nivcotic `superiniection A studs of the relation of silicosn and silica expo sure io histoplasmosis would b< of theoretic and practical interest. 1 here is no indication that silicosis is asso ciated with increased risk for the development of cancer of the respirators or other systems. When there is combined exposure to silica and other substances such as arsenic, nickel, or chro mate. the increased susceptibility to cancer ap pears to be related to the other material. There is no indication of a svnergistic increase of susceptibilitv to cancer after exposure to such other dust- and silica Diagnosis The diagnosis of silicosis usually depends on his torical and roentgenographic evidence. A his tory of significant exposure to free silica is re quired, This is usuallv obv ious, but occasionally the source ol silica mav not be apparent, partic ular! v in mixed exposure. In the case of brick yard workers, the exposure to silica brick that lines the kilns mav be overlooked; the clay bricks contain little or no iree silica. In another in stance, an apparently safe amorphous silica (e g., diatomaceous earth) may be rendered toxic by heating to near or above the temperature of crystallization (55). Roentgenographic changes provide the evi dence that exposure has in fact produced lung disease. The individual elements that combine to form the pathology of silicosis are seen on chest roentgenograms as characteristic shadows. The roentgenographic features of silicosis have been known for more than 50 years (18, 19, 91). In the simple forms of the disease, rounded nod ules are the basic elements (figure 4). In the complicated forms, massive densities predomi nate (figure 5) Because of the diagnostic and epidemiologic value of distinguishing these changes, there has been a continuous effort to standardize descriptions of the abnormal shad ows. Originally, the descriptions were based on panerns composed of small rounded opacities, as seen typically in silicosis and coal worker's pneumoconiosis. It was later recognized that mixed disease was common and that a more use ful classification should also include the small irregular opacities produced by asbestos and oth er noxious inhalants (92). The current Union International Contra Cancre-International La bour Organization classification provides for identification and grading of both rounded and irregular opacities. Four grades of profusion (0-1-2-3) are used. After assigning a grade, the reviewer has an opportunity to reconsider his or her original choice and to designate a second grade of greater, equal, or lesser magnitude, as 654 ZISAIND, JONES, AND WIJHJL Fig. 4. Simple nodular silicosis. appropriate. In this manner, 12 possible sub categories of profusion can be selected, produc ing a 12-pomt scale that results in greater preci sion and sensitivity when a panel of readers is used (93). The resulting data can then be com pared with exposure, clinical, functional, and pathologic data (94). In addition to this grading of simple opacities, the current scheme allows description of complicated disease on the basis of the size of opacities > I cm. The classification also provides for grading of pleural changes, a modification of special value in dealing with the effects of asbestos exposure. The lesions of silicosis are usually more prom inent within the upper lung fields. They may be difficult to distinguish in the early forms of the simple disease and at this stage may be more readily detected on 15 oblique projections (95). The same effect may be obtained on standard oblique views or on lateral views in which the fine lesions are superimposed. The nodules, which are rounded and fairly uniform in size in simple disease, may later show' coalescence as a result of infection or the beginning of massive fibrosis. As mentioned above, the development of massive change mav itself be an indication of SILICOSIS b55 combination by mv<-.>bacieriai infection In mi ner' with mi umatoii arthritis. massive changes are more prevalent and opacities of one to sev eral ceninneiers mav enlarge more rapidlv than expttied. A hird foim of rheumatoid pneumo coniosis is rapid eniargemeii' of disseminated smaii opac iri'-s (96). Roentgenographic progression of simple discase ui fiuni siiupir lu complicated disease, tan usually lie expe ted within 5 vears (26). Mas-es usually occur within the upper lobes and are ottei associated with contracnon of the lobe-., elevation of tht lung roots, and the devel opment ot emphvsematous changes at the bases. Although alcificanon of pulmonary nodules is rare, lvmpn nodes mav calcify, producing an eggshell' appearan-e. Enlargement of lvmph nodes is common anc mav occur before pulmo nary nodttlanon YVYhin the mediastinum en largement mav be fvreme. leading to compres sion of the superior ena cava and the esopha gus ~6j Massive disease with contraction of the upper lobes is frequently associated with thickening o' the pit ura. and with pleural ad hesions. Pneumothorax is not unusual in silicouiberculosis or massive fibrosis and is often a pre-terminal complication. I he so-called acute form of the disease is char acterized bv widespread involvement of both lungs The air spaces are filled; there are associat ed interstitial changes, with poorly defined nodulation demonstrable at the periphery. The lung volumes arc obviouslv small and the dia phragm is high Although infection is often pres ent. cavities can rarely be demonstrated, and the infectious exudates are concealed within the lar ger exudates produced by reaction to the dust. This applies to fungal as well as mycobacterial infections; nocaxdia can complicate silicoproteinosis at well as idiopathic pulmonary alveolar proteinosis. In mixed exposures to respirable silica and as bestos, patients may show roentgenographic changes associated with either or both tvpes of dust, it is not unusual to see both rounded and irregular opacities within the lung fields, as well as fibrous and calcified pleural plaques (Q7) Exposed workers without roentgenographic Fig 5 Complicated silicosis with conglomerate massive shadows. Z1SKIMD. JOKZ3. AND WEILL caJ findings and often shows roentgenographic improvement with corticosteroid treatment. .Massive opacities of silicosis have been mistaken for cancer and vice versa. It should be noted that clubbing of the digits is most unusual in silico sis. Diffuse carcinomatosis and simple silicosis mav hate similar roentgenographic appearances, but the patient suffering from carcinomatosis or dinarily shows severe clinical and lung function al abnormalities. Infectious granulomas mav provide problems of differential or simultaneous diagnosis. Large opacities in the upper zones that are clearly separated from the pleura (pro ducing the characteristic "angel's wings" appear SILICOSIS 657 arnt'i favo' a diagnosis of silicosis (figure 6',. WV.fi Mnnl.r denseies in irncobacirrial infec tion. glean ' eontai with the pleuraJ surface is expected. > emote pleural reactions favor a diag nosis of mvobactenal infection. The simultantcui- diagnosis ol silnosis and mvcobac teriosis can f>e extrcmi \ difficult. The silicotic nodules mav be caught ip in the tuberculous process, and iniphuemaiom basilar changes mav spread the remaining nodules, making them difficult to dete< In the presence of massive 'uberculous (b inges silicosis n tv be suspected onlv when tin re is w idespread uniform small nodulation. remote from lfie tuberculous foci. Other pneu moconioses mas mimic the roentgenographic ap pearanct o! silicosis In this connection it should be remembered th.c welders, for example, mav wotk neai sandblasters and develop silicosis ffigun 7). sidetosis or hoth. Ordmaniv, a lung biopsv is not required to establish the diagnosis ol silicosis; the combina tion of a bistort .1 significant silica exposure and a rliai acteristi roentgenogram will suffice Biopsv must sometimes be undertaken in ex posed persons because the roentgenographic ab normality is thought to be atypical. This has been the case in some patients who have diffuse alveolar filling or diffuse interstitial reactions as the result of heavy dust exposure (figure 8). Bi opsv mav be needed when there is complicating auto immune disease, or in other cases showing progressive and rapid deterioration (figures 9A, 9B) Biopsy may also be needed where there has been exposure to more than one type of dust, lender any of the above circumstances, histologic information mav be of crucial importance in legal proceedings. When lung biopsi is required, an open chest procedure is preferable. Needle biopsy is inadvisab'e because of coexisting emphysematous c flanges. Needle and transbronchoscopic biop sies do not yield sufficient tissue for the special studies that are often necessary. Conventional histologic examination is sufficient for diagno sis when it shows the cellular reaction and hya line nodules in differing stages of formation. ig 7 W ilder with complicated silicosis who was employed in sandblasting operations. SILICOSIS 659 Fig !< sandblast r with scleroderma exhibiting rapid progression of silicosis in less than one year. When rfit tissue t attern is not characteristic, examination unde; polarized light may demon, strate doubly refrai tile particles of silica. When iu'the: diaracieriz tion is required fine parti cles of quartz can '>e demonstrated in scanning electron microscope The presence of excess sili con ma\ in demonstrated bv x-rav energy spec trometry High si lie on-sulphur ratios determined b\ this method arc diagnostic for pneumocon iosis and ire strongly suggestive of silicosis. When tissues corn, in silicates rather than free silica, x-ra' energy spectrometry mav disclose the presence m unusual amounts of associated ele ments stu i, as calcium, magnesium, or iron (98). These elegant met t ods should be applied to all biopsv and autopsy specimens from dust-exposed pe-sotu that show obscure or arvpic a! changes or; rounne tissue < xaminanon. These methods will not only provide improved diagnosis in in dividual tases put "ill widen our awareness ol known hazards ant' disclose unsuspected sources ol 'lust exposure Lung Function it is difficult to propound genera) statements about lung function in silicosis. This is due to the wide \arietv of clinical and pathologic forms ol the disease. This variation is due partly to the exposure variables of intensity and dura tion and to the tvpe of silicious dust. Infections and immune reactions mav complicate the dis ease and affect lung function. The effects of age and tobacco are not easily assessed, because most silicotics are older men who have smoked for main veais. To add to the confusion, most of the cross sectional studies of lung function and silicosis have examined miners, quarrymen, or foundry workers Mixed dust exposures are the rule in those occupations, and free silica usually com prises less than half of the total and respirable tins- exposure Industrial bronchitis is common in such populations, and symptoms and func tional abnormalities mav correlate better with smoking than with dust exposure (99-101). Heaw exposures to relatively pure, respirable tree silica or; the other hand produce the less common accelerated or acute forms of silicosis i H7 Inw ins 7'ltese forms are rapidly progres sive. and lung function data differ from that 660 ZISKXND, JONES, AND WE ILL found in the more ordinary form of silicosis Animal studies are even more limited in applicability: Enormous doses of dust are generallv given in a short period, or in a single dose. The experimental pathology frequently differs greativ from numan tissue changes, thwarting trom riie oiuser ans irtrmpt to relate dircctlv the animals' functional hange to the human disease. The foregoing seem to express an "uncertaintv print iple" wherein the more confident one is that he is studying pure silicosis, the less confident he mav be in applying his results to Tie ordinary human disease. It is not surprising, then, to find apparent con tradictions in the literature of lung function. In vestigators have focused on the fibrotic or em physematous aspects of silicosis (106-111). Tung diffusing capacity in various studies has shown a rather wide range of correlations with other measures of functional impairment (112-- I!9). Static and dynamic compliance are often reduced in silicosis (120-121). T he difficulty of applying invasive tests (such as compliance and arterial gas studies) lo working populations has iciaidcd study of the early phases of develop ment of pneumoconioses. Arterial oxvgen ten sions mav be normal both it rest and during ex ercise (122) Measurement of resistance of the lower airwaves requires a plethvsmograph, sub stantial time, and good subject cooperation, so has not been widely applied to exposed popula tions. The procedure vields limited additional information when the forced expiratory spiro gram is abnormal. Pulmonary mixing is im paired in a large percentage of silicotics but is more sensitive to bronchitis (123). The-e varied functional abnormalities are eas ier to understand if the lung pathology is re viewed. Focal dust collections are often peri bronchiolar, in excellent location for producing a disturbance of ventilatory distribution, and, later, obstruction of the acinus. Focal fibrosis can obliterate peripheral airways. Overall, more gen eralized fiberosis tends to reduce lung size, where as obstruction of expiration leads to enlarge ment of lung volume. When conglomerate mass es form, they not only produce restriction per se as does any space-occupying lesion), but they commonly distort, compress, and even obliterate laiger airwavs. Vessels are similarly affected. 1 he discontinuous, asymmetric lung changes in sili cosis contrast with those in asbestosis and ex plain the wider range of functional abnormali ties in silicosis. Despite the complex pathophysiology, howev er, the following statements seem to have wide support. (I) In simple silicosis, clinical tests of ventilatory function are often normal (30, 100, 111, 120, 124). We found this to be true even for a group of sandblasters with heavy exposure o pure quartz: The relative vouth of that .group uueaii age, :i7 years) probably minimized die effect of smoking (105). (2) Series of sympto matic silicotics will include patients with restric tion. obsiruction, and mixed patterns of ventila tory impairment (105, 111, 122). (3) Compli cated cases show reduced diffusing capacities and exercise induced hypoxemia (125). (4) Lung compliance is usually reduced (120). (5) Ter minal cases have severe restrictive impairments, t6) Severe hypoxemia dominates the last phase of the disease. Selection of lung function tests has recently been reviewed (126, 127). Aside from simple spirometry, a test may have differing utility in clinical, survey, or disability evaluation testing. No functional measurement, or combination of measurements, is specific for silicosis. Serial test ing of silicotics is highly desirable because the course ol progression in the ordinary form of this disease has not received adequate study. Treatment Unfortunately, there is no specific treatment for silicosis and current therapy is directed entirely at complications. Anti-tuberculosis drugs are ef fective in sterilizing the sputum of infected pa tients, but massive changes have frequently pro gressed after institution of the appropriate drugs. Drug treatment should begin with suspicion of infection and should not await confirmation by cultures. A positive tuberculin test constitutes strong evidence of mycobacterial infection. The high proportion of atypical mycobacteria war rants the initial use of 3 anti-tuberculous drugs, including rifampin. The physician should not be anxious to discontinue treatment after 2 years, especially if there is cavitation or con tinued roentgenographic progression. The phy sician must also be alert to the possibility of other infections and vigorous in their treatment. When auto immune diseases complicate silicosis, corticosteroids should be tried. When obstruc tion forms part of the functional impairment, bronchodilators mav be used; a surprising per centage of obstructed patients will show signifi cant improvement. Pneumothorax is treated with chest tube drainage, but with poor results in the advanced case. Heart failure is treated in the ordinary way, but this may produce only movc-st relief of 'ironic ti\ prif a Digitalis .ho'dd be u -ed i:artrull\ u, avoid complicating rhvthm di-t urbance- Phlebotomy is rurelv requiud. 11r need fo supplemental oxygen is a prointncnt It attire o! the iatet stages of she dis ease Veil til.i son failure, unless precipitated be acute infection or sedation, is a terminal event A number ol compounds ,'iave received ex perimental s'ucK in rrevtimon or treatment of sificosis. Of best, oolwinv! jjvridine .\-oxide has shown itie greatest promise; a related drug is receiving < lim; al tr ai 129i Prevention Win re sihea exposui is moderate, as in mines, (jiiames. potteries. and foundries, workers mac bt jj"otteted <>\ impis c ing ven ilation and be the use ol wet technique,. In some cases, materials mac be substituted lor those containing free sil ica. In mam instance , however, such substitutes are not available or suitable 01 are adopted slowh because ol rheir ttr s. Respnators an required when the i oncentrati in of respirable fret silica exceeds the threshold limit came be more than 5 times. At such level dust masks can be useful if the work is carried out foi short periods of time When tic ivoik is piotongcd, suili icspna- tors produce too great a resistance to air flow and become intolerable. All masks used in work with free siliia must completely exclude the am bient unfiheied air, 1 tefects along the seams and evegiasses greatlv reduce the value of the masks. With verv high concentration- of tree silica, as produced be blasting with white sunti, workers require air supplied abrasive blasting hoods. These devices must be checked to be sure that the air flowing through the hoods is not contam inated bv dust or oil. hat the pressure is reduced sufficiently to prevent excessive noise within the hood and that the flow raie is still high enough to evr hide ,utrv ol ambient air Flow rates should be in the range of ,H to 6 cu ft per min. Work practices should prescribe the wearing of hoods during period- of blasting and for suffi cient time afterward.' to allow dispersal of the dangerous cloud ol suspended respirable silica. Associated workers should Unit often do not) wear appropriate protective equipment One can bt optimisttc about the eventual con trol ol silicosis despite nationa: statistics from industrial countries that show housands ol new cases as late as 1965 (27) Recent results from the l nited Kingdom and from certain industries in the United States indicate that tht disease can be controlled Wit! b> tei control of the environ ment and the observance ol modern standards for air quality, workers will be exposed to lower concentrations of free silica. This approach will eliminate most of the cases produced by the tra ditional sources of silicosis. For dangerous oper ations such as sandblasting, the only effective solution can bt the substitution of less noxious abrasive materials. New potential sources of ex posure will appear with additional uses for sili ca. The risk ol silicosis will always be present in mining; recent advances in mine safety should be universalis applied With continued progress in occupational health, it is our hope that silico sis will become a medical curiosity rather than an important cause ol disability and prema t lire death Arknmrtedgment The w riter- thank Dr Herbert Ichinose for supphing photomicrographs. References ]. Zaidi, S H : Experimental Pneumoconiosis, Johns Hopkins Press. Baltimore, 1969. 2 Hunter. D.t Tin Diseases of Occupations, Lit tle. Brown, and Companv, Boston, 1955. p. 841. .1. Silicosis and Asbestosis, A. J. Lanza, ed., Ox ford Iniversitv Press New York. 1988. p. 5. 4 Hoses A. I) , Trasko, V M., and Ashe. H. B.t Control ol Silicosis in Vermont Granite Indus try: Progress Report. Publication 557, L'. S. Department of Health, Education, and Welfare, W ashington, I). C... 1957. p. 10. 5. Middleton, E. L : The present position of sili cosis in industr. in Britain, Br Med J, 1929, 2, 485. 6. Gardner, L. L : Pathoiogv of the so-called "acute " silicosis, Am J Public Health, 1933, 23, 1240. 7 Bucchner, H A , and Ansari, A.: Acute silicoproteinosis, Dis Chest. 1969, 55, 174. 8 Mckerrow, C.: Silicosis and coalworkers' pneumoconiosis, in Clinical Aspects of Inhaled Panicles, D. C. 4. Muir, ed., E. A. Davis & Cu., Philadelphia. 1972, pp 156-172. 9 Cochrane, A L Epidemiology of coalworkers' pneumoconiosis, in Industrial Pulmonary Dis eases, E. J king and C M. Fletcher, ed., J and A Churchill. Ltd London, 1960, pp 221-231. 10 Gough. ]., and Heppleston A. G.: The pathol ogy of the pneumoconioses, in Industrial Pulmonars Disease F_ j. king and C. M. Fletcher, ed.. j and A C nurdiil! Ltd., London, 1960, pp. 23-36. 11 Hamilton, A., and Hardv, H. L.: Industrial Toxirologv ed 3 Publishing Sciences Group, Inc., Acton, Mass., pp 429-440 12 Theriault, G P,, Burgess, W A., DiBerardinis, 1. ).. and Peters. 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