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Spencer's Pathology of the Lung Fifth Edition EDITOR P. S. Haslefon, M.D. Consultant Histapathologist Wythenshawe Hospital Honorary Reader In Histopathoiogy University ofManchester Manchester. United kingdom }* McGraw-Hill Health Professions Division l ( New York St Louis San Francisco Auckland Bogota Caracas Lisbon' London Madrid Mexico City Milan Montreal New Delhi San Juan Singapore Sydney Tokyo Toronto Eastern Virginia Medical School Moorman Memorial Library P. O. Box 1930 Norfolk, VA. 23501! / HWBUI0009208 McGraw-Hill A Division ofTheMcGrow-Hitt Campania Spencer's Pathology of the Lung, Fifth Edition Copyright 1996,1985,1977,1968.1962 by The McGraw-Hill Companies, Inc. All rights reserved. Printed in the United States of America. Except as permitted under the United States Copyright Act of-1976, no part of this publication may be reproduced or distributed in any form or by any means, or stored in a data base or retrieval system, without the prior written permission ofthe publisher. , 1234567890 KGP KGP 9876 ISBN Q-Q7-10S44fl-0 This book was set in MeUor by Better Graphics, Inc. - The editors were Martin J. Wonsiewicz and Steven Melvin; the production supervisor was Clare Stanley. Quebecor Printing/Kingsport was printer and binder. : This book is printed on acid-free paper. c- Library of Congress Cataloging-in-Publication Data Spencer's pathology of thMung.--5th ed. / editor, P.S. Hasleton. p. cm. Rev. ed. of: Pathology of the lung / H. Spencer. 4th ed. 1985. Includes bibliographical references and index. ISBN 0-07-105448-0 (alk. paper) 1. Lungs--Diseases. I. Spencer. Herbert. Pathology of the lung. n. Hasleton, P. S. [DNLM: 1. Lung Diseases. WF 600 S746 1996) RC756.S65 1996 : S1S.2'407--dc20 DNLM/DL.C for Library of Congress 95-19711 HWBUI0009209 15Chapter OccupationalLung Disease A. R?mbbs- " Zeokerfirstcoined.the termpnsumoconiosisforlung DEPOSITION AND CLEARANCE OF,PARTICLES disease caused by inhalation of dust Today many " different forms' of.pneumoc'onioses axe known,'each - Airborne particles .possess a range of shapes .and may caused by different dusts, fiimes, smokes, vapors, on. . exist individually or as aggregates and. this will affect gases. The definition ofpneumoconiosis varies; some their deposition' in the human respiratory, tract, .. authors restricting it to the nonneoplasfic reaction of: Particles that are near to a sphere are designated com- . the lungs, to inhaled minerals or organic dusts .ex- . pact and those ffiat-have-a length-to-breadth ratio of . :' eluding asthma, bronchitis, add' -emphysema,1 3:1;or greater'as fibers.-Some authorities require a where'as.othfers,.including myself, use the terni'mdre minimum length of Snin to designate a. particle ' widely to encompass any .pulmonary reaction to fibrous.'Particles arer deposited in. the respiratory inhaled-particles, from an industriai source. The tract according to their stze, density, shape and aero- exposure,may not necessarily be by direct exposure dynamic properties and by the volume of each inspi- to a particular mineral within ah Industry but can be ration.3"3 Those in the size -range of .1 to Spun . from neighborhood or dorn^stic. (paradccupatio&al) -r aerodynamic equivalent diameter fAED) are the most exposures,.-. , _ ; ": likely to deposit in the lung parenchyma. Particles of The damage, caused by inhalation' of different extreme shape.stichaS'fibers andplates.andpartid.es types of mineral particles varies according to1 the of very low density show a- greater tendency , to cumulative exposure, size, shape, surface properties, dpposit m the airway waUsVThe.. likelihood of fiber and durability of the particles. It should be realizeddeposition within the lung depends mainly on the .. that minerals given the same name but originating diameter because'those'with'diameters below 3p.in . froth different locatiods.and.processes may vary in align axially witHm'tHe afr stream. The majority of .1 physido'qh'emical'properties, .and thus'biologic activ- fibers .that deposit In the King have diameters less, * ity. This :is" particularly, important wth. regard to than ;3pm but may.exceed 200/um m lengtli. Short... asbestos-and talc.-, t .i hi; .. ' ' ,' fibers (<Sf/ita iii length) reachthe lung parenchyma Immudologid processes axe also involved fo;a more readily than long fibers (>Spm in length)... , variable extent intha response ofthe lungs to mineral because the latter exhibit greater aerodynamic drag, expbsiirei! They: are.;;important. for example, in which increases impaction and sedimentation in the <ronic herylliosis.. add .extrinsic allergic''alveolitis; larger airways.Aggregation of particles effectively .. Also 'individual! variability, exists in deposition arid increases their AED, which will reduce deposition retention of partieles-.and the.presence bf other dis- within.the respiratory, tract Particle size also inflq- eases (e.g;, rheumatoid ;disease). can modify' the ences the toxicity of a miiierai. response1 to'the'deposited particles. J ' The pattern andrate of breathing also influence Clearance mechanisms are important. It has been particle deposition. Because the internal volume of estimated that a nonsmoking. city dweller inhales the airways increases with successive generations, about l'g of particulate matter each year, about half of the net effect of normal breathing at the level of the which isdeposited in .the respiratory tract. Without respiratory bronchioles is that the(forward air flow- efficient clearance mechanisms die lungs of an iridi- virtually cepses. However, with- heavy exertion -the vidual would "silt up" at a young age. Smokers flow velocity increases add this increases the deposi- inhale even greater quantities of particulate mater- tion of.particlesr--in the upper airways by impaction ial--about 150 g/y from 20 cigarettes per day.* and within the smaller airways by sedimentation and . 461 HWBUI0009210 462 SPENCER'S PATHOLOGY OF THE LUNG diffusion.7 The nose is more efficient than the mouth cause pulmonary changes. Also the experiments at removing particles from the air. Ail particles often utilize relatively short high exposures that do greater than Sfim in diameter are removed from the not reflect the lower long-term exposures that occur air by impaction in the nose. Mouth breathing in in human beings. creases the number of particles that can reach the Intratracheal exposures result in a very uneven lower respiratory tract. deposition of mineral particles quite unlike that Clearance of particles from the lung depends on occurring in the normal state. Intrapleural and a number of factors including the anatomic site of intraperitoneal procedures bypass the normal deposition, particle solubility, particle size and defense mechanisms and deliver considerably higher shape, the efficiency of the phagocytic system, the doses of a mineral to the mesothelium than Would presence of fibrosis, and cigarette smoking. Soluble occur in life. Mesotheliomas might occur in serosal particles dissolve in the lung secretions, but insolu membranes when a fibrous particle is directly ble particles within the acinus either lie free or implanted, but this is irrelevant if the particle cannot within macrophages and may then move to the cili normally penetrate the. membrane. ated epithelium whereby they.can be .cleared by the Inhalation studies are the most appropriate, but mucociliary apparatus. Some, particles within the great care has-to.be taken in conducting 'these; the acinus, however; may. .penetrate epithelial mem mineral used should be well characterized and sized, branes and' enter ihe interstitum,8"10 which is more dosage should be appropriate and s&fidateTong-term likely to lead'to fibrosis; This is particularly, fljcely to human exposures, and appropriate Controls should: -. happen when the'macrophage system becomes over be used.- Unfortunately^ wefl-conciucted' inhalation loaded by .heavy? dustfrurdeps. The particlesibteated! studies . are extremely" expensive arid technically within the ihterSfiUummayrgain access'tome vascu-' demanding.-; : : ; lar and lymphatic-systems and may then be carried to Interpretation.ofin yifrb and`ih vivo data*on-the other organs; the visceral-plgura, or regional lymph " pathogenicity, qf a specific mineral should be done in nodes.11 This is reflectedJn the black, outlining of ' conjunction with, the i|uman epidemiologic.-patho- subple'ural'- lymphatic- pathways observed . in the logic.i and pulmonary mineral burd'eh-efidence. It is . lungs of urban dwellers and coal,workers. There is a imp'ottant that unjiisfified conclusions.should not be greater retention ;oflarge compared tosniall compact: made about human consequences' of- exposure to a . and fibrous particles within the lungs.. Also the pres mineral only from in vitro and in vivo studies; They ence of fibrosis within aTung interferes with compact. should be regarded as'screeaing procedures. - - and fibrous -particle clearance. Tobacco' smoking impedes particle :;clearan,ce by interfering with the mucociliary-'actipri sndipossibly.macrdpiiage. func-\ PATTERNS OF DiSEASE : " don:12,19 -Substantial gyidence .indicates^ that for--;many lung diseases.caused by mineral particle expo-" Mineral exposures dan produce - almost the whole sureyit"is the'retained mineral particle bidden' that is gamut of. pulmonary pathology,'; Table--.15-1,-gives important in pathogenesis.. ,''' v',r'" examples;18 A pathologist conftbnted by almost any formpf pulmonary disease should consider mineral, exposures in the list of etiologies. Of course, some IN VITRO AND iN;V|v6 sTl|piES : types of pulmonary patholbgy are more closely asso ciated with.mineral exposures than others. When a . Experimental studies .provide usefiil information subject develops a pulmonaiy-'disease a good-and; concerning the -effects of mineral 'exposures ;dn- the - complete occupational history from commencement . lung 'and pleura..*'1 However, when considering the-- of,w,ork is .essential because the pathologic sequelae value of in vitro and in .vivo experiments with min may not develop until several decades after exposure . eral particles in rejafion to the likelihood of develop-, (latency). The occupational histories, ofrelatives may ing human disease, certain limitations and criticisms also need to be ascertained because some diseases should be kept in mind.1? Experimental procedures (e.g., berylliosis and mesothelioma) may result from use artificial "pure'j.and heavy exposures to a partic-. indirect paraoccupational exposures. Also it may be uiar mineral, often, causing'overload of the raacro- necessary to ask about hobbies and pastimes because phage'system in animals, It should be realized that in: these cani result sometimes in exposure to.hazardous such heavy doses even relatively inert dusts cam, minerals. '. ' .. j- HWBUI000921 Chapter IS / Occupational Lang Disease 463 TABLE 15-1 Types of Pathologic Reaction That May Occur with Various Minerals Compartment Type ofReaction Examples Airways ` - Airways--parenchyma Asthma Bronchiolitis Centrilobular dust accumulations Isocyanates, metals nitrogen dioxide Parenchyma.. * v *.. Diffuse--random ! ` Pleura Slight fibrosis Moderate stellate : fibrosis . Marked circumscribed ! fibrosis Diffuse interstitial fibrosis Extrinsic allergic alveolitis Sarcoid-like ; Diffuse alveolar damage' DIP. ' .gip' . Pulmonary alveolar , proteinosis Emphysema ,.PMF. .Carcinoma , Infection.. Benign effusion Plaques 'Diffuse fibrosis Mesothelioma Coal, kaolin, talc, mica Silica plus silicates or.. ' iron Silica . Asbestos, kaolin, talc. Fanner's lung Beryllium Toxic fumes Asbestos, silica, silicates Hard metal Silica . Coal, cadmium Goal, kaolin, talc " Asbestos, nickel, arsenic Tubercle in silicosis-. Asbestos Asbestos; talc, ' ' ' woliastoriite : Asbestos .: . . Asbestos adve interstitial pheumodia; GIF 'giant call interstitial pneumonia; PMF = ;tve massive fibrosis ' ,, ' ;;ia: '. GENERAL APPROACH TO INTERPRETATION bF -PATHOLOGiO SPECIMENS.:- .. V.' / Pneumoconioses have . important connotations medicolegally and-a careful, macroscopic examina tion and recording- of lesions frqm specimens of lung and 'plfeyia is essentialrtif the;:.pathologist wishes to_avoid cohsiderablev.dif&culdes;. and. potential 'embaiassme'hts later oh: Oftencorrelations between path'ology arid radiology and lung.function tests will oe necessary to correctly diagnose and attribute dis ability or death to a mineral exposure. It" Is wise to retain lung tissue from such cases for a considerable .period of time, if possible, becausa.sometimes issues are raised that were not initially considered. Adequate sampling for histologic,examination should be performed. Itis important to take samples from m$jiy areas of the liing and to include, badc; ground, limg as well as! tiimor 'when- considering..an , occupationai caiise'for minors.' It is necess'ajqr to. sam ple frpra freas' away from frie tumor and preferably from the other liihg to evaluate`fibrosis, when tumor is present. At least one block should be taJs.en. from each lobe to include the most abnormal, normal, and intermediate areas and-at least one block from the major airways, pleura, and lymph nodes. Table is-2 is a suggested schema for evaiuatmg,and-.recording macroscopic findings of the iungs..and-pleura.*7:- . The microscopic assessment-follows the usual procedure for any pulmonarydisease, namely, first of all a IdvfrpoWer examination-to. decide which anatomic Compartment, the disease is in followed by higher-power examination to characterize the nature ofthe cellular and any particulate component. HWBUI0009212 rl ' 3 464 SPENCER'S PATHOLOGY OF THE LUNG TABLE 15-2 ..... industrial processes. Historical evidence, of Macroscopic Recording, ofLung Diseases pneumoconiosis; including silicosis, has been Associated with Occupational Exposures described in Egyptian mumxnies.-- Bohemian miners Primacy dustfoci / ...... Average size (grade 0-3) 1 = 1-3 mm; 2 = 4-5 mm; 3 = > 5 mm Profusion (grade CP3) v Proportion of lobules involved: : . in the sixteenth century,20 and stone cutters in the eighteenth century.21 With ' the coming of the Industrial Revolution many new trades developed in the United Kingdom; the danger of occupational dust inhalation was not appreciated and the-incidence of silicosis rose. It was during this period that occupa 1 = <33%; 2 = 33-66%; 3 = >66% tional diseases first began to be studied seriously In Secondary dustfoci - 1831, Thackrah began a study of longevity of British Number ofstellate foci according to size workmen in. dusty trades and found that sandstone Number ofround foci according to size . workers, died on average before the age of 40 years.22 Size of PMF tesion(s) ' Emphysema ' Type ... Centriacinar, panacinar, irregular Severity (grade 0-3) 1 = 1--3 mm; 2 - 4-5 mm; 3 = >5 mm Profusion (grade 0-3 ..... Proportion of lobules-involved (similar to dust foci) The first use of the term silicosis has been credited to . Visconti in 1870.23 The South African authorities . and investigators provided several important reports oh the prevalence of disease in gold miners and inau gurated compensation schemes and improved venti lation systems at the mines in the first 20 years of the twentieth: century.21* Just after the commencement of the'twentieth century sandblasting with silica was introduced, which resulted La many, cases of a partic Interstitialfibrosis. ularly fulminating form of silicosis,23 fn the United Severity (grade 0-4)--microscopic States at Gauley Bridge, in the early 1930s, silicosis ' Extent (grade 0-3) affected a large number of tunnelers.26'These cases (< 1 =** up to 10% of the lung involved , led to die establishment of occupational dust stan 2 = involvement of 10-25 % dards. Regulations have become increasingly tighter, 3 => involvement of >25% in developed countries over the past 50 years. Cases of silicosis are still observed although they are PMF *> progressive massive fibrosis . uncommon. In underdeveloped countries the disease' Souses: Modified from Gibbs and Seai,lr courtesy of the editor of - is still a significant-problem. Journal ofClinical Pathology. The effect of. silica inhalation on the lung In some cases the pathologic examination will -''hot provide the complete, answer, to diagnosis and -^attribution. an.d .:mixteralpgic. examination of lung tis sue will-be .advantageous.* This Has''been used most v-extensively ;in%.asbestos-related diseases but if can also provide-useful information.in assessing silicate arid metalrinduced diseases.,' depends on the dose and duratibn.of exposure, the size of the particles, the mineral form (polymorph), the pr.esmme 0f associated minerals, individual vari ability, "and':presence of mycobacterial/.infection. Relatively high exposures to} finely..partic4l.a(e^ilica dust, such as has occurred in sandblasters ahd'.silica flour vlorkers. can-lead to the-acute form of silico.sis . (silicoproteihosis), whereas prolonged-exposure: .to lowfer fibses-can lead to the typical chronic fonr^of rmiCA'- : silicosis/Sihca exists naturally, in .crystalline :,ah.d amorphous' forms. Amorphous, forms include opal The word silica is derived fronuthe Larin noun silex, and flint, the farmer hydrated form being, found in . a flint,-a stofte' that .contains silica (silicon dioxide). diatoiruaceous earth (kieseiguhr). These are relatively .' Pneumoeohiosisj caused by the inhalation of dusts norifibrogenic unless heated to,high temperatures containing a large proportion ofsilica is called silico when the crystalline forms, cristobalite and tridy- sis and it is a disease as old as the history of man him rnite, are produced. There are several natural crys self.. fjfntil the discovery of the-tubercle bacillus by talline- forms, which include a quartz, the most Koch in 1882,'silicosis was confused with tuberculo common form arid which is usually meant by the sis, a disease to which it predisposes and with which terms silica and quartz. The others are tridymite, it is often associated. Because silica and silicates are cristobalite, stishovite, and.coesite. The latter two , the most common constituents of the earth's crust, forms are very rare. Tridymite and cristobalite are dusts containing them constitute an important oc formed when quartz is subjected to high tempera cupational hazard in mining and innumerable tures. for example, in refractories; experimentally it HWBUI0009213 Chapter tS / OccupationalLungDisease 465 ' appeared be more fibrogenic than quartz. Virtually all iLiim^.e^qSureSrito-iiiica 'lire associated with varying aihounts qf' qthet>:ttiinaials, paitioiiarly 'datasKtod^jLhbsermE-^b'd^^ffie/respqase to silica dqpendihg.ou theft toncentStibn and their own min- g|Jc%ib|p>p&^^fc'.'^ii^:|jb^ Effects of.slftci'and othernimterajs aiS'iednsidlesed to;lje roughly;in `b^l- ar^.;^lefppni^,|^Bi^re45o as.irfixedidtlstfibrd- . p^optfnanjt,'^fre rift5ponse,is Is.alsp.izfdd* ^^|lvanaddn:in;r^'pbns`e^o^^e.e3qpqsxires,;ihQst n0.dce&jd'iin'&'QWiVq& .^'e xHeihnatoid diadiesis (^|iilan's:;.q]nid|i>^);ia^tb.rm. of.silicosis preciis- -die risk '4s tp'sjliqa butyfith- qd^ra^d^pfic fltt vi&q and injyiyb studies r/HivepisfidSw^i'tiiat. ^Ife^^ieaaSlc?.-M, silica '9U^^vfhe-'m^^'ian^\vhciPeiice''bf-n^rcbl)acte* with cumulative exposure to .respirable silica.29-30 Lesions may progress .after cessation of.exposure and the subject may present'clinically several years after exposure has ceasedi^cufe iiWCpSisvlsilicp lipopro- teinosis) develops withni' 3. years\of heavy' exposure, is usually rapidly'fatal, and showsra different pathol ogy to the other forms. ' * ". ; ../sAf?! " ' ; . .v,^ >1;.; .'*.'* Chronic lNpdu(qr^.^i^eiK|9^^^S -1?' ' Macroscqplcffl^%elungs'incBhomc;sdx|psfi,^yeal firm, gra^fs^t'a^' cumsatibed,'whQrlednO'dhliaftthaiard;j|i6s!fepmyaIen.t. in the Up^'^njsl^^yy^^a[^i^rpi^|i^fii'ters in diameter to-large 'rdfssivV i^fp^^s^^lSl|sive fibrosis (PMFJJde'sibns^that can oo^|q^^^s-of the lung"and .can extend acrpss.`fi^^^ mtq*pfe:k'(ijacent lobe `(Fig. lS*i The P^EF'i'esiidns :rih-_mpSt' See- "r i. r ,. . fev- ; .; i4 ,.-.. . V:- yi ,> . . ii-gi.-&; Sources' o'f Exposure y.,f\ '; *.A.V .;S- T|fere;;d^;:.m;hn^,p6lBntial occupational sources pf e^qs&edddusj^opntainiEgaliigh.propb'rtiobof.sp;icS ^d,pi9se:.tt^t.^ie^y'^nQ::iftble .15-3 are by'.iip f- ':''.. \'.t : ;{' - '... ...'-'V-;--' ' .-. . Clfrild'diTecrtUi'es ' -'- -*;>&&..-\,,\\.. Generally chronic; (classical or. nodular) silicosis develops after more than 20 years of exposure; uncommonly cases develop within 5 to 10 years of expostpewhen thetenn accelerated silicosis is used. The phmology ftp&qiiar inbqth forinsllSjhnptoms or sigas-:are. nb.tfusu^yiprqsent in..tbesimple. form but #hrch pib|^se^j(idffi>^.^eatfEih'r^b?og^'opadties. Radidgrapbdc and functional- abhoniielities correlate present tfenfers^t: the smaller nddul'e^^d'die'isassiygi-l^siqiisit^ qayiitate and may-sbntam^ifa^sh^ht^-flM^^d^i;payttatipn has . usudll^ife^Sied' Sd^|-ie^imb.:-'tfe^tisis. But sdmetimes.it kksfeepxibsiused by.iii^epba^efiisifec- . tion. In the la^erf&sS, the .cavities dften.''cdfitaSii:^ay '. ftiable . indiwdualfhmd^p.dides^p-ball^'cSi^lq^sritipn. This co'ntrristsi^vd^'%q.;mb^iyeJjesipiis^f^n'm:|he . majority of -casSS fof'coal1worker'^ ^j^e^oi^S^Siosis and silicatoses*..yrhidli -are diffuse' and sbft;'in contrasV.td coal; wbrker% pheUmocoiubsis,:fpcdl:empliy* semais not'd feature of silicosis. The;plfeujrhl surfaces frequently show firm, fibrous idhetibas'to the chest wall and there may be areas of pleufil tiiickening. In. the,earliest stages of the disease the nodules will.be observedM. .the subpleural tissues'mb-as:.tbp'di^eaSe progresses they will be .-seen.iii the remainder^f the TABLE I%3 ' >. Industries, with:PQ$sibIe Silica Exposure v- . Mining andniilling.of;nearly.all iiietals and nonmetals . (partying, of gramte^fedstone, and.slate Gr^te'^d stone.industiies, ;. -.- IrSn and Steel foundries1 |o=: .. '. Manufacture of gldis, pottery, andceramics MahUfocturp.ofrefifactories': . Manufacture of abnisive powders Enameling --..; . . ~ Boiler.scaling . Steel manufacture Rubber industry- Processing of diatomacecms earth______' parenchyma. The hilar lymph nodes typically jte enlarged and contain whorled, hard, often calcified nodules (Fig. 15-2) which is responsible,for the "egg shell" calcification. often present in chbst 'radio graphs. The. changes in the lymph nodes develbp before those in. the .Ijmg and if nodules are ' absent from the lung-the diagnosis of silicosis should not be ' made. , - - ... ...*. 7-. Microscopically, the well-developed silicotic nodule, which.is the hallmark of exposure- to dusts with a high percentage, of silica, consists of concen tric layers ofhyaline fibrous tissue at its center with a peripheral zone of dust-laden macrophages, fibro blasts, and chronic inflammatory ceils of yanable width, which extends out irregularly into the adja cent interstitial tissues31 (Figs. i5-3 and 1S-4). The center of the nodule can exhibit necrosis and calcifi- HWBUI0009214 J Gough-Weatworth whole lung section from a North Wales slate .. worHsrshows numerous silicotic nodules with ah area'of pro-:^- gressiye massive fibrosis formed by conglomeration of nodules .in the upper lohe. . cation. The necrosis is usually a consequence - of . ischemia from the formation of nodules obliterating pulmonary arterioles and perivascular lymphatics. Even so, whenever jconsplcuous necrosis is. seen, even in the absence|_of granulomas, direct staining and culture for acid-fast bacilli should be performed to exclude mycobacterial infection. The evolution of these silicotic nodules has been traced in animals and man. The earliest lesion con sists of collections of free dust particles and dustcontaining macrophages situated in the alveoli and interstitial tissues around the respiratory bronchi oles; alveolar ducts, septa, and beneath the pleura. This is followed by the development of retieulin and collagen fibers, at first irregularly, and then at the FIGURE 15-3 . Numerous rounded, well-demarcated nodules in the lung of n Norfh Wales slate worker. (Low power.) 466 i HWBUI0009215 fChapter IS Occupational Lung Disease 467 FIGURE 15-4 .A silicotic nodule shows centra! necrosis with calcification-, an intenediate.zaae ' of circumferentially arranged collagen, and a peripheral-zoos ofdust-laden', . macrophages intermingled WitK'iiillaih- matory cells. (Low power.) ' c. center of tite lesions (Fig. 15-5). With progression the cehtel-zone .takes jOn a cqnceatric laminar arrange ment and the dust-containing, macrophagei' orient perihfa.erally. TMs leads; to obliteration of the bron- `cfaidlar and vascular architecture. Often nodules at different stages.can be vis^uaffzed in tHe'same limg. Under polarized light the. .mineral particles at the centers of the nodules exhibit dull birefringence (quartz)-, whereas those in the peripheral zone'exhibit strong.'birefrmgence (silicates' and quartz). From the abdW'deseriptiahdt will be appreciated that silicotic lesions MeMuch more, fibrous than those seen in coal wdrK&'s-pneumoconiosis. " . ' *! INURSTmAlflSROSIS' ... V'~ . .""-j .On microscopic examination of-lungs of.-subjects exposed.to silica .and silicates it is not uncommon to find foci of interstitial, fibrosis in:dddition.tosth.e.typical silicotic' nodules.' Occasionally the interstitial fibrosis is sufficiehtiy:severe to'be associated,with honeycombing. The precise contributions ..of silica and silicates to'these lesions have not been clarified. Rheumatoid Pneumocqnibste In subjects with the rheumatoid diathesis the nod ules may deveISp more quickly and become laigejnd !. FIGURE 15-5 An "early" silicotic nodule in a North Wales slate worker shows a large collec tion of dust-laden macrophages and inflammatory, cells with fibrosis at the center. (Low power.) '. HWBUI0009216 468 SPENCER'S PATHOLOGY OF THE LUNG set within a background of relatively sparse small nodules, as they do in the Caplan form .of coal, worker's pneumoconiosis.32 This has been described ' in association with silica exposures oh rare occa sions. Interestingly, it has been claimed that there is an increased incidence and prevalence .of rheumatoid arthritis, systemic lupus erythematosus, and'-scleroderma among workers exposed to silica,'.but not nec essarily in the presence of silicosis, possibly due to the immunologic abnormalities set off by the expo-" sure.' 3`3-34 Others have not found this to be ^s.of . ica.4 ;4! Experimental studies have, shown carcino genicity in the rat but hotthe hamstecor mouse42 and this has been linked to fibrogeriesis. Human studies have provided conflicting-results and have been dif ficult to interpret becafoseof confounding factors -such as tobacco.usage, radon exposure, and other industrial carGihdgenS'pigt have, not been adequately considered. A recent fe.vlew of the subject concluded that lung cahcec*shd}il4;4'qt' hh elassified;:as an occu pational diseasfoliifofodt&Ai|ica^^ V. Acufe Silicosis CSi|icpjiroleiriipsis> Pathogenesis . /-. . -"`-This pattern a-fyactton;occuis.ih ass.ociation. with In vitro and in vivo studies have shown that the tox . - .high-dose expd'sufe's.tq'feely-.p^cnilate .aystalline icity ofsilica-an,d its polymorphs depends on particle size'and surfeceproperties.3 As the particle size dis-. . ers;'ani silica floih' w'drkers.^ln.confest toiheptlier'. tribution diminishes .the cytotoxicity increases. The crystallinity of the particle's surface'reflects the silanol and ionized silanol groups; the former deter mine mineral-cell attachment and the latter, deter mines the interaction. The. presence of trace metals, such as iron, and aluminium,' witinii'the silica parti cle can modify the surface interaction by bioeking-the ionized silanok.groups,, which results in a lower fibrotic response,.A key e.vent is thefoptake and inter action between the silica particles'and macrophages, which causes'damage to lysosomal membranes. This causes release of chemical attractants. which in crease macrophage production and release. Death of some of the macrophages causes release of the sil;. ica particles^ that-are then: rephagocytosed by more * forms' of ?^eiop- relatively trapidly- over a few-years. Clinically, there -is breatth- lessriess and the chest mdlpgraph fsS#inbles that of edema. ., , It is characterized by filling of the alveolar - , spaces . with granular, eosihophifie:. material that stains.positively with the peridSic acid-rSoh|ff:lPAS) reaction, and is also-rich ih'lipi'd fFig. 1S-&}..There, is hyperplasia and metlapiasiaof tibifofype. Hpneumo- -cytes and an excess of these cells hasfo.feea found oh ' bronchoalv'eolax' lavage?4 It is sisnilarpto idiopathic . Lipoproteinosis'fiut 'tends to' show more.; interstitial , inflammation'ford fibrosisi which is-.sfotito be.a.pse- ful differential diagnostic -feature. 'VVe'll-deyel.aped ; silicotic noddles are usua&ly absent; although there -may be, focal collections'of'dtistdadenjrnacxophages macrophages; Some of: the macrophages, however, will survive and carry the particles to other parts of . the lung.. There is evidence that polymorph neu trophils are also involved in the inflammatory, with slight acrotints of central, rfibrosis present. Polarization often, but not always.shows large num bers of birefringent particles. Mineral analysis of the process and that there is direct damage'in"type^i;;; pneumocytes in the centrilobular'Iocation in the..;- A simfl^'^eriditipn-iiTitoi- early found ph.ase.38 Macrophages containing quartz, are : in the bronchoalveolar lavage fluidf -of sill-" ' ' '"Inals' by. inhfoatioh ofylafge-i^gio.uiits .of. quaftz, . tridymifei*. and. mstqbfoife,pa^.<4es;-.pver short'.peri cotics and the percentage increases with deration of. ; ods .-of tinie,4t?7:fyihi&h"; 'damagei^fodT-acti^vatesV. the exposure.37 Macrophages and neutrophils'damaged type.II pneumocytes causmgahfoxcfsAtelease pflfon- by silica can release oxidants, which can result in \inated bodies containing p^'^^d.'widgli.'ab^u- degradation of connective tissue components-ofThe mulates in the alVeblar.'Spdc'eA-^T'fe^is followed -by ~ lung and epithelial damage.38 The macrophages^an type II pneumbeyte Jhyperplasia aiid fiirtherirelaase release factors, such as interleukin-1,'. wHiclfostiifiu- "* of pho'sphoiipid..There is^alsojayidehce pf ;ifopafoed lates helper thymus-derived lymphocytes and' fibro ...phagocytosis and clearance-pf. the. lipid,matorifo':;and blast growth factors, which may lead totfiorosis.3? The specific roles of these various factors and how , ;. particulate matter.48 : "A:-... they interact are still being elucidated. Mixed -Oust Fibrosis . v" SIUCOSIS AMD LUNG CANCER .P . There has been considerable debate for severafyears about the carcinogenic potential of crystalline sil- This term was coined to imply concomitant exposur j tolsilica, -in.combihationi'-with less,'fobrogexiic- dtrits - such as .iron .oxides,' carbon, kaolin, aiid--iriica.-- ; HWBUI0009217 * . ?* '. , FIGURE15-6 . ,, ' " Acute siUcoprotsinosis shows a granular - aesUuiar in.aaalveolarexudale.(Low power.] :: . - v-"-' - r; clmicopathoiogic features of these pneumoconioses ''"msausa|&ad"-- ^showmany s^laride;;., >~corfg^aSf^^l?paV^^trk^0^pbsv,6itijieally Kaolin -Pneumoconiosis _ . 10 <p&jSseilt^:i^{sgmeit is ^^ardgcxal mstmction because these lesions are frequently'found^alongside =; .(iical1 silicotic, nodules and virtually all exposures lb silica are associated with exposures tp other min erals. Typical'bfrcdpatioris where these iesions have been described include hematite workers^ foundry workers, arc welders, china stone workers, and a : small proportion of coal workers. .. . .y%W<3ipHeV^t '/"./v" ; --. Kablin or chmaclay-waSi &scavered.in.a hill of ex truded gfamteih-CbraW&ih' Great Britamia i;750 by William Cuckworthy. It has been use.dm.the United Ktogdoin arid abroad or2tbe:'mamJa.ctuie,,of porce lain,. as a fillet'and tahtihgyfonpaper,.and in; th.e, rub- bet;' pfastxps'f Md-ftjli2m:;:mdusixi8S.:Jt'has ilso been e^ipit'eifi'pm deposits.m Devon and from sediinentary'deposits m-^abrgia.'and South.Gatoiina . ih-;hemad'teim|hers;-grayish s.wotkets.^ahihjItayiSh black in T-i^^^^|^.'|^eU.ericis^^ni9St;^B^aIen|u3: the . . *ust ; y^Stht^ficnSfiuJe contains acent^hyaiihized collagen. y;/-^4^l.';M^^-;-P^4phepalr ;zp.ne: bpinposed. of radi- .. 0 ^il|y#S^-^mSexly amiigect - ddllbge'hsahd reticulin ': .^iithts5ihtefmihgled with "dust'iadeEC 'ma.crdphages .. .. -;'i -;c ^ip.feATES,. ; ; ... /. The nonfibrqUs silicates are a large grdup.of minerals that .are-widespread and have ah extensive range of industrial-uses.:Pulmonary disease has.been associ ated with exposure to these minerals in a number of different industries.30 They are less Ebrogenic than silica and asbestos, and pulmonary disease has been observed only after heavy prolonged exposures. The FI&ure 15-7 , -. .... Mixed dust Sbcotic aoduies.with stellate margins and central col- iagetuzation superimposed-oa simpla macular lesidas ofcoal .^vorker's pcaurnocorijosis associated with emphysema. (Low power.)' ` .... .. - - 469 HWBUI0009218 in the United States. To a lesser extent.it has also been . produced in Australia, Brazil, France, Spain, and Germany. . During the commercial preparation and purifica-- tion of china clay the granite, mica,..and quartz are allowed to sediment out, the lighter feadlin.particles v' being carried away in suspension. Npwadays, thekaolin is then allowed to settle and dry put using SI-,. ter presses and mechanized drying, plants.- Formerly- open kilns and the transfer of storage linhays, wagons, or bags vfeS;:accpn^lisHed; -: ' by hand. After drying,.,the process, jnyasf-dusty' but'.:; . ...'/since 1970 the dust levels have, been dfimadcSly;V ; ifedtifced.51 After refining, the.maia Gbnstlttten.tj(3fthV material is kaolinite and tore may he/'itp;to iO per cent mica but quartz is less than 1 percent. Several radiologic surveys of workers from this ' industry' in 'Cornwall32''5' and- ;Geofgias.*,S8 have shown a pneumoconiosis generally characterized by small rounded opacities but occasionally EMF! Pneumoconiosis is generally seen ifi thS inillers; bag- ;. * >' ;gers,r and:lbaders;/where .the dust,is-dry. Exposures'. after 1974'are not.'consideredjikeiy-to le.ad to pneu- moconidsis;-. .. .. ' ' In some ofrthe;previously. reportecl,rrases of kaolin pneumoconio.sis- it-, has -been^suggestpd that quartz Was responsible. In the past some..of tEe. china. 'clary workers had also worked .with china stone and FIGURE 15-8 , V Theiung ofa Coraiih'chinkcliy Workat^hows a havitajtedgny- i's"*h white pto^^v9'ta^ye'fibsc'is.^ML-.Mi.tt upper;parf of the lower in these subjects pathologic examination of.the lungs revealed silicotic and mixed dust fibrotic nodules. _ -`Howeyer, -there.rare-cases .of pneumpconipsis that ,> j Zr_ii^i -ii_ rritirtv^^h-the .'^^iG^n^a.clayiwdrkdfs^exposiire--and.in.these V4../v -gross ekpmination the luhgs show'rifayi;spft:stel-;. hldte lesibrisVbetsveena.and 7 mm id diameter. Rarely *' -3 ^pfssive.- lesions ,may;'be-.seep'.aad.thds.e ^e: ..diffuse " ; masses' of.'dust-lddeh particles. .-axey first "Pbserved .'.'^{kadl|he;^Spira,tbhy.bronchioles but with increasf.;iBg/si'zn^eyjexterid along theSyeplar'fiucts.and the v.iriterstitiuxn of tEeadjacent^yeflU (Figs;4S-9 mid 15>-/19):'^Lesions from ad.jacehf;lpbUifS;'may lml|4tip to ifiyeidiffu.se interstitial collections and"frie ftvtosis. The particles are strongly bkefrmgent''on polariza tion. Ferruginous bodies, formed on the platy parti cles,may be present but usually are not conspicuous. The massive lesions Consist of masses of dustdaden particles mixed with randomly arranged 'collagen, fibers. Mineral analysis of the lung tissue from sub- 470 FIGURE.JS-9 ...... Extensive interstitial collections of dust-laden macrophages in the lung of a Cornish chinaclay worker. (Low power.) ; HWBUI0009219 D-'t FIGUREJ5-J0. ; .-.IntersUUidcqUecttaMof&iist-tadeh . Enacrqphagss associated with slight Sbrqr Sis urdie lung of a Cornish china clay. . wOrkeii'CLow power.).. . |ecb exposed to'china'day. shdw a .similar" composi-- monary disease*, to talc exposure, in workersJem- - . liofi' tp; tEtf origimal dust38r. >90. percent kaolinite, ployed in secondary industries "because the nupqrak. ;< i'^fdentiquartz;'.< i percent feldspat, 1 toTO per- to; wbitdvfhp.y ivyere e^osed'xnay not hevtaic.-^-far .; -'cent'lmcai-1;5' ... example,; ip thejtire.|ii^fe'Jifiica';'and.i feqlin:.w;efej " 'ffi;sdimriary, it is possible to develop a pneumo often.ysed instead"oftaldfor various applications.;,,. coniosis' from exposure to kaolin in.the absence of - Talc has hfeh.'iised'in many 'industries. (Table, r qup^jwheaexpSsittes afe heavy. However, with the 15r4h PpImgnapy'.fibrCi'sIS has been associated-.with,. unprovement in the hygpene. conditions of me'indus- try;imce'the early 1970s-this problem, is likely to`dis-- appeiS" *" been described, yvitb "fertiary exposure.:to vdf^smgtic, talc.- Ifre question nrisbs as to-' Whether tfa^jiuxtg, Talc Pneumoconiosis .v changes.jyere caused by the tald or nontal'c-.cpmpp-. nentsqr whethfi. the'.e^bsure" was to a diffe^entffiip---. Talc or hydrated magnesium silicate erpli completely the only way.io&settlg: this. (MgjSi4Ol0(OH]z) is formed during the breakdown question in an ih&viduM'Case ,is. by-ihineral toriysis, . an(d weathering of serpentine, tremoLite, anthophyl- of the lung-tissues,-which is difficult and requires a , lite, anti rocks of similar nature. It is found in.and has range ofsophisticated techniques. A recent study of a! . been, exploited from, the United States,- Canada,;; . France,, Norway, India, Australia, ItaiyJ5pain,;:.ahci Austria. Commercial talcs can contain a4 number.'h?" impurities that will depend on thegeolpgic.sbiJice of the material. In some products the percentageiofrion- talc mineral will be greater than lhat.,pf'di|''talc:;,:for example, the "talc" from New York State :cphf?uh5 : approximately 3.0 to SS percent hemoiite an^i2- tq;50 percent-talc. Approximately 50 percentpf the world's . , other minerals 8<Mf3 Death? shortly after extremely tonnage of talc contains predominantly Mc;.(9Sper-:: cent or more); in the other SO percent talc is. associ- ated with variable percentages (10 to 50 percent) of TABLE, if*!'.-; 'f carbonates or chlorites.39 A further cbmplicatibh is . Indus&ieS:With 'P.ostsibla Talc Exposure that some, products sold as "talcs" may not e^en con ..^Ceramics tain the mineral tdlc. Therefore, one shpuldibe cau-. Paper. ". -4- . Tires J. ", ' Rubber . V- yir' tious m-interpretihg Studies of pulmonary disease in one cohort of talc workers 'and'exhapojatiiigTheihto' "Plastics' Cosmetics and pharmaceuticals other cohorts exposed to'different varieties., of talcs.: . /Building materials. , Animal feeds Particular care has to be taken in attributing' pul ' Paints pj ' Fertilizers _ __ 471 HWBUI0009220 % 472 SPENCER'S PATHOLOGY OF THE LUNG high exposures to talc have been reported rarely, but ' lady an^ged :cqliagen.:;0ther..featiifes'iiiclude fer-... these have been due to suffocation rather than the' ruginous.bodies formed.on ta3c;^Lftes, which candsevu, toxic effects on the lung. A range of radiographic, '...mistaken for asbestos:bodies, 'forei^.ibpdy-,^aiuji6Vi' ' lesions has been reported in association with talc, ... mas containing uncontaminated by amphiboles. including fine retie-: .. (Fig. ;i5-i4), and j ular infiltrates, honeycombing, PMF, and pleural', ; ris -uncertain, at tii^ pjr^'eat - tiudbte;-w^guL^r. . thickening. - ' -;;are'a genuine feature . finding in a Jew PATHOLOGY ... 'Strongly, bhefrihgfent 'platy itfhd' i On gross examination of the cut surfaces of the. lungs /{Figi 15-15). there are stellate.gray macules, which in severe cases,. . .. ," link'up and are.-associated with honeycombing (Fig. 15-11). Less'; edmmonly. present 'are palpable: gray : ;7<^ciNpi^ '.-`W* ^ ,./ ' ' nodules. PMF lesions ^characterized by a diffuse ' '".-Some, reports.,have., daimed.;,^ _? soft gray appearance, which may occupy most of ' ';.itdigdahey'^EW'^posub'o^^^.M^^h|raSl-i-.r... an upper lobe, sometimes cavitated, have been mated by amphibole minerals. Thislias iha^ly'eenf-'.: described occasionaUy.-f0f*,S4 tvficroscopicaUy, the teed around the New York State talc yvorkers who . most'cormflbndesions .are stellate interstitial collec were.exposad to a high proportion of amphibole min tions ' of-: dust-ladea^piacrophages associated with erals in addition/ to taler Severalrmvestigatprs. have mild fibrosis situated around^e.respiratory bronchi-: argued-that the.'amphibole' cdmponentiiS'.tihti^'hesti-.,',-i . oles (Figs. i5nl2i.90i.;i5-^3jl/i,i^esSioii of'these form and therefore' not hazardous.^f^f lEa^y^cQ^oxt' .'' lesions resultsm linking up of adjacentlesions that it-. studies,of. this group found an excess mortali^'^m ! widespread >wiU lead.to. greater fibrosis and honey lung.cancer, but'thiS was in short^term-workep ydui':' combing. Severe .'pathologic -.conges are usually less than a year's work; there was no.-rejatioa ta.dura-, associated with ,ve^~ high, mineral burdens. Less tion.of.exposure and the effect-ofismpking^w^.ispt . t composed of dust-laden macrophages with a greater amount of collagen. Mixed dust ,fibrotic nodules may be present'-when there, is ^.ociated quartz exposure.. Ph^ Iesi'o'ns.are characterized by.largb collections of dust and. dust-laden macrophages bdixed'with irregu- talc workers'and'cbmpOTsons iyith- the-Vej^ .oni workers, who were exposed to talc free of abjji boles, indicated that there was no causal cahnecfibn- between lung cancer and amphiboles in the New Yprk State workers.Til'7t "' c-l-. -t;' .. .-,5 .. h-rf v v :' =v :..V :r<i ' -'/uv; FIGURE IS-? J - Lung from 3' worker in the rubber industry showing interstitial fibrosis-with Sq htm- eycambiog. Analysis ot tije luSg tissue.. shows significant quantities oftalc. .-... kaolin, arid mica; (Courtesy ofthe:editocof HumatiPathologyTM} . ' HWBUI0009221 ChapterlS 1 Occupational Lung Disease 473 ^URi`15^ata"le w ork"e.' r sho. w' s int'er>stitial eoite'ctfdfu; ofdust-iaden c ell-sassociated with.# mild degree.,of. fib.r.osis. [Eow. power.} :>;3sr': s J V.. V -r--. Liang feifrajralc worker shows'accumu- Jafiddpf&tf.pkticuIstejniaiBriaJ^d inflarnjMtoryceUi'and atetruginoiis ^.dyarrowj.-.pyleciium power.] . HWBUI0009222 Occasional'.- cases of pneumoconiosis and pleural ." thickening have been described in association with 'prolonged exposures/2773 ' v PATHOLOGY.. . ' '' y. Ort gross 'examination thejung shows gray, sofi stel:" lateTfesiohs :thatmeaSuffe a. few miiiiifte'ters ipMiame. terkRarelytmassive'-'Iesiohs haveheeh-teporfed^Fig. ^5^16). The';Sii^.i^oitu'^ay;'^nk$jp to. give, a fine ' -.mtersfitiS'pattern, Microscopic ^Kammatipri shows ";-i3HtialIy:,.dustrla,den f the walls, ofj^.9dj^ceht<al^|ij^^d'falyebla|^|icts. .>* ^ M M A M frX* ^ *ll m J : CC,* M M ' A1 1 loqr ' of.-.dust-i; fibrosisiT . .. ...................... .................... . F!GSmeiS-l4 '..y;/ ` " Particulate material composed pred&ruosua.Ely of talc presets! in macrophages and foreign ofHuman Petholagy?i)/\ /*. ' uhdefr.pplarized:ii^t.t-;.Ferrugindi^f\i3g^.p^if^|ie& on "the yello^sllhratojti'mica plates aruTfareiga body y .giant ceils ma^be observed^^^-fFig/lS-l?}. ' --V/ /v:';-v/ '-j -''-Ft4lleffsr^c^Fh'.(|i)f|MiTiooonio^te' - Mica Pneumoconiosis;. -<; k ; . .. Thire^s some Cdnfiisio'h as to what is understood by tb termbfayierls earth.because it does nat-meamthe The term mica, for practical purposes, encompasses..: iam.e miner^(s):lS-.-eve^^ooipib^/-&7^^-.Uldted the minerals miisdoyite, phlogopitS; aad verimailite..' .'-ljes it incibdes-.an .attapM^feMplciuniV^angs of Micas are produced in India, Brazil. Madagascar, the- . ;prodacts/iyhereasdti:th8-UmfedjK!ingdpto.ik'rbfers to United States, France, Spain, Finland, and China. calcium montmorillo'mte dhly/it'&ai^tidng abspcp- These minerals have beeti used in-paints, plastics, . tive properties and is used in animal feeds, pet litter, fire protection boards, pigments, oilwell drilling pharmaceuticals,' herbicides,1 -and 'the=..prQces.sipg of muds, the electrical industry, and textured coatings; woolen garments. Some fuller's earihs contain signif Exposures to relatively pure micas have occurred icant quantities of quartz, but there have been rare mainly in the grinding and packing of the minerals. cases of pneumoconiosis described in association HWBUI0009223 . with, heavy-' prolonjg^d;.''exp9^^^:(:6 fidjer's earth uncontamuiatedby (juE^^'fof'feSiiupiey iff workers at the Redhill; and ^United Kingdom:"-*!disability and the'radip'lpgic'cbangesdi.ave'usually taken several: decades to develop. PATHOLOGY .. In those exposed.to Ml^ ea^ viithoufcq;ftart? the . macroscopic changes have consisted of gray-black stellate nodular lesions' measuring a few millimeters on diameter. Mkdoscopii:. examination shows .peri- 'shronchiolar and'intfKtiti^'^lB^|^w|M^liden miacrdphaiges asspda'ted'^i% aiMi^if-degme; df,fibro sis |Fig. xS-18). TheJparticlesi, die. itton^iyf_.fixefrin' "gent`under ')'T- Mica grinder--numeqjsis.steJUaee gray lesions. FIGURE IS-17 Mica bagger. The lung shows finely particulate gray-brown mate rial in macrophages and foreign body giant cells in association with ferruginous bodies. COAL - Goal has been minedyfor over a thousand years in Great Britain, '-being fix?t mqntibne'd in' the'Sajcoia. GhrOriicle ofPe'terbor.ou^ih.B.5.2/L'ae:nhgcdescribed coal worker's, pneumoconiosis..in. lBi9?r wOk .the coming of the Industrial. Revolution in the first half of the nineeeenQi .centthy .the.;C^al. ruining industry :the 'many occupational hazards' ' of cbal- mining became recognized in:'ScqdahdV78-Ih 1838, .a -foung Scots doctor (Stratton) coined'the term ahthracosis to describe the black discolored lungs of Fifesfiire miners.79 - -.......J --ivi Inl938,aMe.<h.caI.Res8.arch'Councii;{lldEG)'isur- vey was set up, ofnoal nnhef's-jpneiMdtioniosis- in South Wales because the incidehcq'Was In^er ih this than in any other fjrLtish.coal fiel^i This'survey; con tributed1 to much ofj^.q: knowt^%e ;df''^s:Tprin:6f pneumoconiosis with regard;"^q^'d^^fu^cili-knciio^' logic-, histopathologic,, and e^pemh'shtal' -a^ects. The--survey also.included aa'^^nVe gdologib and petrologic study;of. thq-miixqs. 'and^d^nSScitidn :of the different aspects p|ni4e du's.t'Th'e header seeking detaffed irffonnadoa on .tinssubfeet .is referred to.the Medical Research Spedai'Reports Of lt42, i943,'aad The term coal worker's pnetmtocoUiosis (CWP) is now used to cover a variety of pulmonary radiologic and pathologic change.^, resulting from the inhalation' of coal dust and its impurities. In addition, to causing pneumoeoniotic changes in various cate gories of underground workers. Godgh80 showed that coal trimmers employed In loading Coil into ships' holds might also develop similar pneumoeoniotic lesions. This and the previous MRC studies settled 475 HWBUI0009224 the dispute as Ip whether GWp'Was caused by coaler TABLE 15-5 . silica exposure, shd^iifg that it.cdufd occur without Determining Factors in Coiil Worker's sigmficantsliica exfipstire.-In GreatSnfain. G^VP-bas Pneumoconiosis been recognized as d disease" separate -from-silicosis for the purposes of Industrial benefits since 1.943. ,-Further studies b^thfe MRC in South Wales and the National Coal Board longitudinal study of30,00.0 miners from 25;..British tfoiiieries. has .taken die research further and: allowed realistic , standards pf .respirable dust'exppsqie to be formulated.81-2; ,The reduction in' dust levels'in the mines, decline in Cumulative exposure--dose and duration Particle size distribution Coal rank Concentration, and nature ofsilica . Associate minerals--muscovite, illite-; and kaolin Individual responses Infection-;-- -. numbers of the workforce, early retirement, and the . gradualclpsure of uneconomic' mines, hassled to .a deqline in incidence ofCWP id 'Great.Britain,;urope,. and the United Statas^CWP rarely.develops indoal volatile matter, whereas the, younger, lowfr ranked workers, before the hjge of50 years. ` ..., , . ; coals matter. . The prevalence arid types of pathologic; lesions Inorganic the most observed in CWP depend on several factors: (Table part cliye^^^p.rajetj|s|l,itp'^ari!i |||8^f-which 1.5-5},. which m'aypXpfairi the-varying incidence.in constitutes^^ghir-propri^^t^plltew^thl^ higher differentcoai'.fieids' ind evdh between mingg-.in the - ranked ppaJs:::Gpa|^a^-;^||^nfa^'ari^ber of trace same coal fields.-Fqr'Pxaihple, in'Great Britain it has elemen^;:-.|riGlri^Lfi^amem^lfepdjyna^ariase, tita _. occurred most frequently among miners in the South nium, .pr,esppghi certain Wales, coal field arid especially in- the miners .em low percent). ployed in the deep anthracite mines in, Irtfest on the Glamorgan. lt is also more common among miners type ofv^j:;t(qji^r^^^rta!ifi4v.i|^^a^bck strata. working in pits'/with small, deeply situated coal TherefqrP/^e,jphri.f d|e;.uri|lg^ri^iml worker plays a seams}. very important part and Coals are rich in carbon arid are complex miner- composition: ofShe ^resplrkple.-fiustirtbj^liich the alogically,.. the composition varying from mine to worker is - exposad ;an(l ;.cd^e'q^entlyi.tSe-'fype and mine. Coals are ranked according to calorific value severity;-j&f niay into low, medium, arid high. The higher ranked coals develop.jMuiers^eriiprqyh'd-S's'iiafd^ie'adm'Sj.and rock are the oldest and contain the least amounts, of workers in the corisfruttiomof'cdmmarii'critiiig shafts ) 476 HWBU10009225 Chapter 15 / Occupational Lung Disease 477 between adjacent seams or bridging geologic faults '. Pathology*3 9* work almost entirely in bard siliceous rocks and are exposed to high silica concentrations, "which may The pathology .of CWP is most, appropriately consid- reSult in silicosis rather'.than CWP.' Other groups'of deal workers exposed to high concentrations of silica . ered under five..subdivisiohs: (X) simple CWP, (2) complicated CWP, (3) Caplan lesions, (4) einphy- include firemen and screen workers.. . sema, mid (5) interstitial fibrosis. The'-incidence and progression of CWP,.as one would expect, is. related to cumulative exposure to SIMPLE,CWP . jspirable' dust,1- but this is-not thp whole. story. Macroscopiealiy, this is. characterized by multiple There is also a relationship to coal rank. Several stud bilateral, soft-, stellate,, impalpable, .black, (macidar) ies have shown'' that for equivalent exposures the lesions scattered through the lungs hut wMch.'.are incidence and severity of CWP increases as the rank most'pfevalerit in the.upper-'rivo-thirds (Fig. 15-19). increases.--""-For unknown reasons minem.of.lugh At the earliest stage the lesions, are only slightly ranked coals`show significantly more retention , of . larger than'the soft dust foci associated with urban dust inthe' lujtgs than.those exposed to low.rank ' living. The-lesions vary: from about 1 mm to-fe.V;era1 . coals'; The histologic appeamacesml tbe pueUimoco- millimeters in size but by definition do not exceed. 10 .itodc lesionS also varies;with coal rank.??;8?. Another variable factor is quartz content, which affects, the ofquartz ori-tiie lung and this has als.o,b,een.demon- ' MSCfeAXrM'JS- * , m Sari f> ^'J"'XT11kh. Tis;inMbitya?,*U*** ;amm Aa<IPy(MhAo4*t bfe'pdrihiffe ahd-aiay. vary, with geologic source.90 There is Evidence that cytotoxicity of coalmine dusts inbrbkses as:particle size decreases-whicfr-in^turnjcor- -=--' -- ------------- `91.Some miners- expbsed-tb. dust within high quartz content haije ^Jubited ifiiuSually rapid radiologic changes, of pneuiiiocofiidsis:*? V In.life the diagnosis arid-assessment ofseverity of CWP depends dri th% prevalence aadriize;ofopacifies o%eryed;6ii chest radiographs. It is'.customarily divided intb'two -forms-^simple.and complicated. The criterion for. separation is size of the dust foci .In the ;Iri|^mafipnal.-.imbor;Orgariizafibii-system of jradio- gfdjhic assessnierit 'df pneumdcpnietic iesioim, if an op.a'city.is-pres`entwhich isgr'eater than. ldirlh fiiam;eter then -the. condition is regarded as.iotoplicated CW:or-PMp;-..^rierily,. simple CWP .ismqt assba- ated^^th. s^ptbms.:-or;uclinic^.;signSi7SignifiGant reduction :iri lUrig;:;ftmctioQ. .or reductioii.'.m iongev- ity,8 Complicated...CWE. particularly',when1 lesions .ar^.^p^/IUp^^sfasspcfatj^jwitti.'pri^ti^ve cqugh, breathlessness, ^n.dVsignificant iinpafrmqnt ofdung function-arid it can result'iii;prematufe death,.. Coin- plicated CWP:,is more likely- td develop qri^a-.back- :gr5und of higher grades of simple CWP<* K.-can devblpp several"years, alter leaving the mdri||?y'and . iniriy, experience of South;Wafes coal jnrriers.q.yef,the last decade it'bias .affected elderly, retired miridra .who had sustained exposures several decades ago.' FIGURE 1S-19 . J- Gough-Wentworth wholo lung section fromyfcoai worker of many years shows autneradSblack macules effecting most of the lung lobules, a small number of larger=3tjillata black lesions, and centrilobular emphysema affecting about two-thirds of the lung lobules. - HWBUI0009226 478 SPENCER'S PATHOLOGY OF THE LUNG 'J mm. With, progression they may come to occupy the usually they are superimposed on a. background of 7 majority of the jung lobules. This pathologic picture macules. Other features include dust impregnation of can be seen without there necessarily being any ra- interlobular septa and thripleura; the latter is usually diologically detectable pneumoconiosis. The num focal but occasionally may be diffuse. The peri ber of lesions seen radiologically always appears to bronchial, hilar; arid mediastinal lymph.nodes are be less than is actually demonstrated pathologi often enlarged, densely black and may be soft or firm. cally.95 Associated with these macular lesions are , Sometimes they contain whorled silicotic-like nod- frequently variable degrees of emphysema situated at 7 ules, usually (a the absence of similar lesions in the the centers of the acini (focal .emphysema). There- lung. They are caused by the preferential clearance of . .fore, the black, lesions appear.to be highlighted by silica from theliing to the lymph nodes.97 ' the surrounding: pale emphysematous areas. The Microscoprcaiiy the earliest change consists of radiologic changes of simple GWP are due to the dust the accumulation of dust-laden macrophages around and the small amount of collagen present and do riot the respiratory-bronchioles and;^adjacent alveoli, . reflVct the emphysema.*98 In addition-to.these. inipal- blood vessels, septa, and . beneath the pleura.. Free pafrle'inacular lesions there may be firm,-palpable, dust particles may also be: seen. The macules consist :. black lesions that may be stellate or rounded in shape of uniformly distributed dust particles free or within (fibretic nodules). These nodules are usually much macrophages intermingled with reficulin and small less in number and often larger than the macules (Fig. amounts of collagen,-which contrasts with the con 15-20). Uncommonly they occur on their own but siderable formation of collagen in silicotic nodules (Figs, 15-2l;-to-:15'23j; The.-.dust .packLng of these . lesions ihcrelses-swith. decreasing;.ash content arid iricfeasirigbdai'ranlc^'ThtfriQ.dTilesshow.muchxnore collagen than'the `macules1 ancbiti? arranged, in bun dles that radiate in all directions. Nodules .are associ- ated ;with'the minirig of lower ranked' coals and ; \ " mcreasirig rish-content . Nodule?; may show cayita- .. - don; cilciffcationi and.iGholes;terpl|piefts...If the coil " worker hasTjeeri'expdsed'to' a.rhigh.siiicI concentra- - 4 ' tion, mixed- dust fibredc or silicotic-type. nodui.es. > miy be bbserved/ur.which.case. the collagen fibers ' will either be;arranged in a linear or circumferential '^pattern;-Examination-of. rnactiles. or nodules under 1 " polarized" light may.-reveal .small doubly reftacfile ; ,:i-Z C-'i ; . - _.. .. 77 ..... . .I FIGURE 15-20 Gough-Wentwocth whole lung section from a coal worker shows several stellate black lesions, which were palpable, and centrilob ular emphysema. Simple coal worker's pneumoconiosis shows numerous stellate macular lesions associated with emphysema. (Low power.) HWBUI0009227 w'jTt**"**. ". **.?it- '-/ lap .' - `-A-f>r|/Kr-.:;v>:' r1 } :??< ' ::H|.G08E TS-22 ' ' ?' " - Simple lesioa m.acoal worter.sHowini '*!!?;;>-. ` dust.padurig and relatively indd fibrosis. -r.'XLqwpqwsr.) .o-.'jfV;- : 'partides, which are the sificat& pi^iiiL^thin the cqaldust. .^v'' COMHUCATED CWP OR RMF The. PMF lesions,- ;which by.: defiaitiori; are .`.greater :iion-.l. cm in diameter;' nearl^Siways, occur on-.the background of seve'fif simple-pheuihocpiiiosis. The PMF lesions, most commonly occur in one,or both upper lobes but: can; occur in any lobe: They may reach several centimeters in size and can destroy the whale of a'Tobe; orVsoinetimes several lobes.' The ' lesion is typieaUysoft, jeVbIac,.hbmogeneous, aid well delineate'd;had maji:''S'how;vai0ng degrees of cavitation, (Fig,-15-2$). :;The " cavities - may '.-contain fluid resembling India ink. The affected lpbesmay be adherent to the chest wall.; Microscopically, the lesions are composed of dust particles, both free and within macrophages mixed witffrandomly arranged collagen andr'eticulin fibers (Fig. 15-25). The centers of the; lesions may evince necrosis and cholesterol cleter. There-^':fre4uentiy ghostputlmps'of vess'eis and airways within ithe centers and at the periphery small vessels cuffed by lymphocytes and plasma, cells. Necrosis within PMF lesions is usually a.result of ischemia "rather than infection. Often severe .etaphy^ema.siJ^un(^j?MF lesions.^', __ L ,ib.ecdn.d:'^pe; of PJ^.lesic(n''h^h^^-^fia is MiiiesmidgiS^&s of lung.. MMl^-;3cpnteri.tv^ve'"indicab.di^iidi^^^bt type of PM^-.is'i:s'ociated with exposifre, tb nipS^nk '' cjtflis'md':^.'rs|'pdin,ti type itg;iawet;i^^^d-.;|&ai|i.8'1 .Obviously -these;-Pl^EF,le5i0ils reptllent^^.p^--of a spectrum :'and'ibhe.-'.bften'.en6'oiiritjBR.:,S6me;^.tiL;'in-, terme&at'hfeaftires -thatrara' diffichit'id ciass^.(Fig. ri;5-27j. FIGURE 15-23 Coal worker. In addition to stellate macular lesions, some nod ules show central ceUagenization. (Low power.) ." CAPIAN'S SYNOROlyiS (RHEUMATOID PNEUMpiC<5N(<3SlS) ;.v -In 195,3, Caplail% described ..uripsii^ radiologic changes in Coal miners suffering rfrom rheumatoid ' arthritis,.and stib&gueicttly. radiologists in- G^fpiany. France, Belgium, atfd Holland reported sitnilar find- ingsi The chest radiographs showed large, rounded, and well-defined shadows mainly in the peripheral 379 HWBUI0009228 FIGURE 15*24 '' " .- .Gough-Wentworth whole lung section from a coal worker shows diffusely black progressive massive fibrosis maujly in the upper lobe.-' - " ` ' " FIGURE15-24; .. ; . // Coal'worker. An. area of progressive iriissive fibfissis shows con* glomeradonof nodules and aharea of cavitation; ' partethe-Tung' fields, but unlike .. .the shadows cat&b^^'PJE^.j^y^(e-ii6t Tfstricted ih the upper IpbesV.aSd- tended to ;eaJ^u^^mpt?'ra^id^'.:<ljh6 _ appearance ;of the pplmdnaxy lesIqhssQmetimes pjre- . 'ce^e_d'.the.OEset'o'far&itiC;;lesidiis;'as-.:Ssto'.q'tdmary' pu^on^rheuniatp0hpdSes;%^962;:iCapiahhiid ' cov^brfers?9 'fouhd':;iliatcif5..;perc.ent oftsuch pafidhts showed positive serbiogiehtests for rheumatoid dis- .easei'.^.>.:Ti-... '..' V." \ "" - ..Jn`.l9S5t.Goug^'pid .colleagues100 described the -pathpfogic appear&,c&S:'hf these:.iesionsvThey'?are - "fo'tmtfed or ovafe w$1l*<iemacated.'|ini nbdules^that . may: hV . discrete ;ur.tpo^ueQt .Wig/IS'^Bj.-'rJhey . . ekhib.it'a lammated:appearance with light.aM:`dark layers.rThey-vary from-a:few.niillinxeters to.seyeral \ centimeters in size arid "often, are supdrimpose'd on a background of relatively slight pneumoconiosis: The nodules may show areas of liquefaction, cavitation, and calcification;., i ;rs:- ' . .- Microscopically the central zone of the nodule consists of necrotic collagen, coal dust, and debris. . Dust often lies:in rings'. At the edge of the necrotic 480 HWBUI0009229 nuclear debris {Figs. 15-29. and-15-30).- Outsida^&,' ' fibrapiasdc Eone-thsre is circumferentially arranged ? collagen :and "fiiidieraus lymphocytes:>andpliismh : cells;5-wJblcU sometimes,.Form germinai.'CeAiers; Tbe": ifre-" H?p:;i M ^.Tbs myor.differeritial, diagnosis Includes tuber- -.At/iMa'i'>' akM aIi'iA -pVlAll m1 - and'palljiaded.. fibroBlaste: fD'mdct ;stainijig-;fipr ,iad- * ^& tLn> ----st ?? <h. ?r. _*_ ^>3 s. )CwB *. - --* -- -- ^ ^^^ iesidds.'td^dnie instances^tipwevef,the.; external * -XcapstdSe may - :be '.entirely - . Pnfca^sulated 'ifalferCalous^' HGilRSJS-2^.. .... Progressive njaistVa fibrosislesion 'from a coal .worker shows an.. gl.omSrata form ofcthe.conditiQa. (Low power-) In subjects with rheumatoid artBritisv Ciapian-.; -.= like lesions also have been associated with exposure to other.dusts including silica10*1 and asbestos.102,103 In'fibse^ssociated-with asbestosis concegtric dUst; nngs are seen. EMPHYSEMA AND CV/P zone a cleft-separates it from, the ^adjacent layer.-bfi. sp^4^ft|^Pw%^^blts;'SirhclL-'Sftow variable;;degrees of pallfsadmg.."fjetweeh1, the cellulax;ian'd. necrotic .zones is a' naifoW Belt; of^Heuttophils'.-andf- The,.issiieof cprf.dustexposure and the development'' ofpny>jiy^n5a hy>$encontroyersiaU^if3s tant, because'the .degree of 'fiihbSonailrdisabili,tyctof CWPoonrelhies-betterwith the^^degree of emphysema Kifr' 5TJT J;' .)' MISUSE ! 5-23-; ..... .; ' ' ' c-- Captan's syttdrome-.'.Well-de'roarcated whoried nodules supejirn-' posed on a background of very slight poetiraocbniosis. FIGURE ISt29; ; ... , ' Rounded. weil-demarcatarfconfluent nodules in a coal worker , with rheunliiediid arthritis-^Gaplans syndrome. (Low power.) , \-48l HWBUI0009230 . .BGU?fis-30 . ' -yti -'He;*' ! . ^Gapiaa lesion shows ceritrSl'nBcxgsis'anS . j -iapBri^heid^oaahfMamn3?^^^^: ,,\ \' with palUSadinif (Low pbw&l-.'.^s'-. ,'X>, foci!105,106 the Maior-confounding-fector is-,cigare,t.te.. smoking. A.considerable body of evidence indicates' that chronic bronchitis and emphysema in coal. workers is directly related to tobacco, usage . . .and cumulative.-, exposure. to.. respirable, dust during life.*07-108 Postmortem-studies have also shown that there - is' a significant excess"of emphysema in; coal ' workers with pneumoconiosis whencompared'to-a--nonmining control population.148-1,0 Thxs is specific to centriacinar emphysema and unrelated to panacinar -emphysema.. Its ^occurrence is associated with mcheasing ambunts"ol:ddst'retained in the lungs. an.d tionof tfa'0- dust focus. -This is.where.the phangei-bf centriacihaf emphysema are- also -located-vit. shotuti be noted that similar lesions' may beobsfeJvecl around the carbonaceous dust foci of town dwellers. Centriacinar emphysema, in contrast to focal emphysema, was considered to be accompanied by architectural.destruction.of the acinus from its earli- chi'oles.l*3 .Apart; from die.^cesel^ie'^f^^uSi fd'cis therpafchologicjappearm.cas.aie identical to those;-' seen in noncoal workers wth'Cehtriacihair.emphy-' sema ieeTig^t^M^iS^iy^^e^^-l^Iy an obsteuctivie'itj^ie.'It bai-ax^frotogjass^^rt^^ath . lcumu|auy.ejh'spirabie_c^:Mirtt|^h^Sff;^lS|;|' .' In;'j^&United kd^dg'my.^?^ssg^l^f^%vhs nasnqyuegHavneanuiunasj.a/g!!? $winmu tuai <juet,cr; - accepja^^fe'; report. is nd?shai^/|joun''dary-wherelonehe^el-'ahd'tlte.5 ther Advisbryi-:'Courtcii'^'re c begins. __ ^J :^6cak :empHw8ma'rviras.}'t^B term cdmed . by riisb&u'' -f U- workers soohld be.;addeei to .the presehtprescnbed diseases for Industrial 'InjuryrDisabi^menfyhshsfit- The conditions for compensation j foci'j destruction. _ exceedi^.ZTm^m'd-iameter^&dhptassoCiated^di. aa^~fugc6di^^ra6iad^ii^`."i^g- ~Kgs:-^-S>>^land lS-23): Duguid and Lainbeft"?iffeught that.it.yyas a' form ofcdmpensat'qxy,t;eiriphysema daused-rby mcreasihg. fibrosis, amdhghfimchdh^0fA?'-.dus.t;fqcus over many yeas::41^^Uhp^ii|S;tha^-|thK^^h^ctea' dust focus becomes relatively less and the emphyfee^ matous part more , conspicuous oyer time. The emphysematous changes are locatedht die center, of - the acinus and secondary lobule because of the loca- 1. Underground coal mining for a minimum laggre- gate'o'fZOtyeazs ` v> * 2. A ^eduction of lung capacity at least! liter below expfcfealeyel-:'' 3. A .radiologic pneumocpmbsis category of 1/1 or greater?'" "' h???..* On occasion at autopsy a pathologist vnll 'be- faced with the problem of determining in a coal miner, who has died from "obstructive airways disease'arid.'who 482 %" "5 ' ?E ' m f . i. { m HWBUI0009231 Chapter IS / Occupational Lung.Disease 483 l ; 'ti - has centriacinar. emphysema, whether coal dust ground remains to be determined. The disease exposure was contributory/If the subject has not had appears to run a slower course than cryptogenic^ lung'function tests and a chest radiograph in the last fibrosing alveolitis.114 few years, this might be'difficult. In this situation the pathologist will need.to make a judgment of the likely appearances of the chest x-ray based on the GRAPHITE appearance):of .-.the. dust, foci and emphysema at iiitopsy..Ip. practice for category 1/1 thfere would be This is a natural or synthetic crystalline, form ef.car-. v.-xiahsive simple-coal dust lesions presents ' - bon. Many commercial -forms of natural graphite11- INTERSTITIAL FIBROSIS AND CWP ` ' (plumbago) contain otherminerals such as silica and - -,- . various clays. It is-used in, refractory. ceramiCS.^aiici;' Th|re appearslo be an increasedjreyalence ofiritefstftjal iShipsi's-'ih the dungs :of coal workers, This'hlis b!|h^'6herved;.m bOth- Sodth Wales, and"ET-ft coal' - .... miners ' `and'.:- is;>-:apjpfojdmately. -1.-6. percent114;*15;. Somdtiihes &is eafa-heobseryed-macroscopicallyhut4 Irfinany casbsit is only;seen by.microscopy (Fig-/ 15-31). A radioldgic'-pathologic study of :ireegular crucibles, foundry facings, steel md'frpn.'maflKifec^.; ture, pencils, lubricants, and brake linings.-.SynmeKc graphite is used1 in graphite electrodes,. atoimc'reacT. tors, and lubricants^ .^number- of cases'of grapMtte;;. pneumoconiosis have been descxibli'd.-but-m:'diaSy;) exposure to silica or silicates may have played S'part. in their causation;117 ": opacities in'GWP'hks-indicated thatrdiey represent'a cqmbjhl!ion;dI-iap'hysema and interatttial.fibrosis;, th'e/ihterstadaFfibfdsishan showVarious dpgrees.roT METALS..-; ., ...- ...... '.-LW i V... dustdep'QsiScm.*Ehe precise comaecfionbeLtweeh' the Mtershdkl`fibrosis mx'd coal,dust or worlc under// Pulmonary responses to metals have been..inade quately studied because they tend to occur in small j-j. industries with poorly characterized exposures. . There have been several epidemiologic studies of ' various industries hpt,there have been few ^steni-' - adc pathology sta^qs-Most bf'iEepathblqgietmfop-r madon comes from isolateicbse repbifei wiffi poorly, characterized exposures,'no mineMd^c-analysis-of;, thedun^tissues, and iio ^proper contrcils-for comp.aij . son. This, account is/.highly selective and'-cUscussies;; only )thqse '.metads//with'.fairly' HveUtdocymented;. . effects oh the lung. "Agents thaT-willrnbt-bs cdnsidhi ered are those that predominantly cause responses in organs, outside the respiratory system even though they are inhaled. . ... y .. . h 'I* tre -for human exposures .to occur to the - -- puie metaiiic ferms-but it is; usually, to the oxides or .. ..o.ther:compounds. Not "alVcpatpamds of a toxic bv-metalx?renecessSily''harmful to the lung. A-wide V FIGURE 15-31 Gough-Weacworth whoT8'iuhg"Sectiaa isram a coal worker shows dust-impragnated honeycombing in the posterior and inferior zones. -sure- to metals, which can be in the form of fumes or dusts. .These responses can be acute, chronic, or neo- plastic. The acute response may not develop, imme diately after exposure but may be delayed for some hpurs. Death or complete recovery may follow the, acute response and rarely chronic sequelae such as fibrosis.. Table 15-6 gives a broad classification of the / pathologic reactions' associated with exposures to metals together with examples: As with exposure to other minerals, the responses.will vary with dose, -physicochemical forms, associated minerals, and host factors..11^11! ' HWBUI0009232 484 SPENCEB`s"PATkotSGY OF THE LUNG TABLE-15-6. .. ' Pulmonary Reactions Associated with Reaction Examples Diffuse alveolar damage Beryllium, cadmium, cobalt,-. or acute bro.nchitis manganese, mercury, nickel Industrial asthma 5 ............... : . ^ ' " Chromium; cobalt, nickel. ^" 'platinum--. - - - Emphysema " ''-GadMium - . :- Centrilobujardust...........' acoiniulation with Barium; iron.-tin . . -7 :r,,, . .. . . iimiiaiai'fibrq'sis ' % .V . -' - . Interstitial fib&StS' . Aluminum, cobalt .r -.......... , Dssquam&ve rnEer*, *' aftduifiiabin'- h -. . pnaVi` - * *: // -r Giant cell interstitial' '' - Cobalt (hard metaij - pneumooia 't Alveolar proteinosis Aluminum Granulomatous disease Aluminum, beryllium, titanium Carcinoma of lung Arsenic, chromium, nickel;".', uraniuin Aiurfiinum.; " r-"-..o ,U There;are.nu^prpusrujies^pr'Muiaiiiiiiii meta^ and Its compounds, ^d:^a...cpn|{derabl^'jdumbef r6f workers-- have :been,.;expp^ed,. torffierni ^Sources tif ;ekposure include, baukite ore; smelting of.bhvxi^,(p6pbt?dh Wotkdrsjfthe inhnufac- bird of-abcasives qr e^lqsiyjqS Cdntamirig;aldimnum,-: aaS&'tbe ^fin<^ngv,pqiisbi4^ 'add-Weldijig'- of alu- - ........-.,1 'J-.'.-yyy a.-;. minum. -Various forms of lung disease, the earliest being fibrosis, have been Ifriked to- exposure.to-aluminum in manufacturing'bf processing' factories but they have been rare considering the Ihigedtimbersqf , workers potentially at risk. Some reports have been, difficult to assess, because of concomitant exposures ., to -other minerals. For exampte,;alrimihum:pQtrodrn . workers are exposed to carboii''mbnojdde;rcoal tar. pitch volatiles, .fluorides,. Sdlfor dioxide, 'and :,alumina.120 Bauxite lung (also 'kho^ W-Swyer*s---<j^.. ease, corundum smelter's lung) was first recognized during World War II among a smaii grpuiftif Workers, Riddell.1*2 Reports'from Germany1 dpiihg,^isaMe'. period :descnbed severe' luiig damage pecujpMg'iii ; associationswith"aluMaum- metal --powder; ifc. 1.959,. Mitchell123, 'arid-McCl'adghlin anct cdwprkers *f4 'In.;. .1962 .described -further cases in Britfin. - ' ' " - b'eenissociated-tvith.;exposure. to^ad^mjn.um: an'(i,'its, compdtiiids,1M'?i:i3vTbese are iis.ted'iog^ffier.yvi^i'tiib ass&'iafod:;e^dsures in .'&ble.-'l;5iy..\gqnq'^^ese reactions 'are s'pecific.-to alummum>;ajnd -the;assbciation cannot be made on the bistopathdldgic appearances. alone (Fig. 15-32). However,: the aluminum-associated diffitse interstitial fibrosis pattem.js:msttallyjtttore severe in the upper zones of the t,-;y^W'.,,sYtitW. lOftes v ; TA8U T5*7t- /..f- 'V ' . :Mumhiimi^Asso(:iated 'irionpryReddHopnnss' i- - '-' ' Readtioh--.1 = Exposure.* ,.;.5Diffuse.intersfltial'Bbros'is '' BBaauxite' smelting References. ' ;:X6tixD5otr ..." m ; - .' ; '* Fireworks and explosives ... .. . "....... ' Abrasives1' ,y; - ShayefW1; Rjddtfe -;. DIP :;.v;v; ... GIF Alveolar proteinosis Granulomatous disease -Welding'; ' Polishing , / Welding ' Grinding ; . Grinding /Welding' /.Chemist . " %% VaHytji&h ?VaLm \ 1 ; ^DgiVVqBi et al3it . Herbert et ah110', - ; .V/'-.i1.\;-eicrjmajzel al133 - ' ;.:ri'"Mrfe'-erM^2.v' Chen et .-''-r.'-v.\' , . , . . DeVuyst et al.ua DIP = desquamative interstitial,pneumonia; GIP = giant cell interstitial pneumonia . . . L- HWBUI0009233 FIGURE 15^32 * ' '* SDiffijsBUitefstitial.fibsosisrlpceifaction characterized by intraalveolar cbUec-: ' Asthma-like. symptoms have" been reported id quently enters the body- tkrqugh'the respiratory tract. several groups of workers 'exposed - to'^aluminum and mosheoinspfcupusly affec^ the Icings; However;, compounds,120,134 but it is not certain whether the it-'is #: -multisystem. changes njiy exposure initiates' as'thmamr exacerbates .symptoms occur in the skin,' liver,. Kdney 'spibfen, dnddymp'H'' in subjects with subcliriioal asthma;.': . nodes.3.40 Dermatitis .or chronic sfcm niters-? may An excess of lung cancer has Jbeen described in occur as a local disease or in conjunctibri with sys aluminum production workers: but it is probably linked to-coal tar pitch volatiles.133 temic disease.-; a:- *' 'Acute> bj?jSyiliqsis. follows relatively high expo sures to dusts,; fumes, or mists, whereas the chronic. Barium ' ' ' . > ':". form- may ifollQw Limited or .prolonged' ejqiosure.to . Barium lung (baritosis) can follow the mhalatipn.of dust particles from inspired air or by aspiration of barium suspensions during radiographic procedures. low-doses. Individual, hypersensitivity appear?-tb be involved,, which is. mediated by a specific 'delayedtype hypersensitivity reaction to b^yUiuraK'm^idch. there is proliferation and accumulation .of CD4+ , In the former circumstance, suchas in barytes miners and grinders, the particles will tend to be uniformly and bilaterally distributed, whereas inthe latter; dif- (helper/inducer) T cells in the lungs.141 The disease ; .. is uncommon even though the use of beryllium jri ;~lnd'ub'try has inqreased oyer the last few, decades. cumstfece the particles will accumul|te.m idcafi2e, .those engager!in! - areas. The radiologic changes are dense Butthere is ' fibd'of the/qiptadfrom its.oies, mostcommo^her^l,; usually little functional disability because .mdre-is little associated fibrosis. Microscopically;;theJnngs show alveolar collections of particle-laden.. mac fed in those :whdhaii.d|e'berylliumcoinp'difrtdf.T-h . latter ajb'uSgd.in refractory ceramics, the;,4lectfpmcs .^dus^,^paGeimd.at'dmfc engineering,' |a^djSroHs. . rophages with few other inflammatory "cells.. Thfe ? "fed hf^iliinn metil fed alloy producti63;'Expp|urg particles are refractile and strongly.burefrihgent'"|Ji^i'' '.jp^y-also ocbur; during the feclamah.du dfiscj^gjmef- polarization. als;13.9 Themse; ofberylliiimijd^flourescendhs6^^s Beryllium - '.cedsed in thbldte ISdOs'mid.'eii'iy l95ds;.^4jiidjis- fey'wasthe cause of-ds percentlof die cfiiomdBbiyl- Berylliosis is a disease caused by exposure to :beryls;;I- lipsis cases'listed in.the; tf.S. Berylliosis Case Registry lium metal or its salts. The term waS;first.used,In up to .1966i142 C2as.es of: beiydiosis'hlaimed tmhaye 1935 by Fabroni138 with reference td:^e;xp'erimen: been caused by paraoecupatiohdl and neighborhood tally produced acute form of berylliiim* poisoning,: & : ejpp.dsfife have tieen'fepdfted.-14-'?'45 "' ' - although-an acute disease following befyUiumte^o- . Some -^studiesKhave claimed that exposure to siure was describedin.Germany m.i933.332-.Hafdy beryllium compounds -causes ..an ..-intrSasdd' f and Tabershaw were the first to draW attention ton- :: luhg canter; however, thfe evidence for this is uncon chronic form of berylliosis.138 Beryllium most fre vincing. ' . -- ' 48S HWBUI0009234 486 SPENCER'S PATHOLOGY OF THE LUNG ACUTE BERYLUOSfS interstitium, septa'/ brohchovasciiiar bundles,, and This condition is rare nowadays with modemihdus- subpleural areas.- Occasionally there, is, necrosis triai conditions. Respiratory symptoms of breath within the centers of tbe"'granulioinas.;?,8''^.u5jou of lessness, cyanosis, productive cough, and nasal' ` granulomas may occur' to.glve rise/tofrqslules. that are, discharge manifest within 72 h following a severe 2 to 3 cm in-, diameter.-':-These may shoyv .'marked exposure, but if exposure is lower the onset may take .. - hyalinizariqii. Schaumapn Bodies are/'fr'eqhehtly several weeks. The majority resolve without long presfent/inthe chronic.Ebrotic stage the grandloinas term sequelae, but approximately one-sixth have pro may disappe|r:deavmg- ohIy;.Ehe Scfiaumann bodies gressed to chronic disease. Death has occurred in as their "cailihg card." IhadditaQtt to the grauauldmas about 10 percent of the cases reported.139. ; : . there is -usuadly; a-pfqnot^ced^sdiffusf't:jnterstidal The gross and microscopic appearances.-are chronic j-inflammatoqr- =umltrate,;t;-%hichf' is:..much'- those of diffuse alveolar damage (see Chap, ill,and greater- dian Jhat; usually pbservefl...m cases5iorsar- granulomas are absent. Diagnosis rests'on aMstoryyqf caidosiS'CRig.li'S-SSj.Thexejis-a'vaiiable de^ee\qfdif- exposure' and demonstration of beryllium withirithe . ftwe/Tntersrifial ";'fibrqslS--.:preseriti ,;vdiibH';.hgay: be lung'tissues.'..... _;V accompanied, by' btbnchiblectasls^ongrbbflibing) md brqn^olqalveql^epiA^M-'iEel^gla^iaV'i ' ) - CHRONIC BERYIUOS1S This is, an insidious, disease that can follow the last ' ' The1'fdlidwmg'OTt6ria'fqr.-.&a^qsisV^f;qlu'qhic.' berylliosis have been put forward.M,w .........' exposure tg'beryllium'.with h latent'period varying from l.montb to more tbim .40. years'.' It closely resem bles- ^sarcoidosisj^uwj, can;lead to death'.'from .pub monagtvfibrosis..." . :* =.v X* a} -4-,- Microscopically, the lungs appear contracted and have hosselateH pleural surfaces,, sometimes with thdckening.,,and adhesions. The icut.surface Jiistqty of betyllium exposure . - 2. Consistent clinicp/physiplQgicfpathologic fea- :-!tures--v .Vi!-... '{: /j'r'"-'.P;/-''" 1 3/Presence ofgranulomas.in Ms.$ue, .'.'"h "/ 4. Detection of beryllium .in. tissues. . . ., 1 5. Evidence of berylliumhypersensitivity . shows, variable, degree's'of hMeycdinbiBg,-. which 6. Exclusion of other grgjiulomatbus diseases tends tohe-mpre.conspicuous in the upper zones. h,, ifc:;- .. Micrqs.copiciilyi' the hahmark of the disease is Occupational histories are often - difficult to the/;prsenee,. .of "numerous: noncaseating compact assess because exposure frequently occurred seyeral. epithelioia.,sar'cqiddlkei:^granulomas located in- the years-previously, it is .often mixed, and other granu- 1; i- I1 HWBUI0009235 Chapter 15 l Occupational Lung Disease 487 fcv. .. r.`s-s.-i. lomatous diseases can occur in workers with claimed exposure to beryllium. The, detection of beryllium in liosis needs to be .distinguished include sarcoidosis,. the'granulomas is particularly valuable but unfortu chronic extrinsic allergic alveolitis, and ciyptogeilic nately, because of its low atomic weight, it is one of fibrosing alveolitis^ Table 15-8 gives helpful features ther more problematic minerals, to detect. The laser in differential diagnosis. : micfoprobe miass, spectonietry technique can be applied ;to conventional tissue sections and can' ! ftect elements in ;|qw concentrations^ A recent Cadmium.' ' .' .,;udy using the technique demonstrated berylliuinin Cadmium is_.,used in the manufacture . of alloys;/ the granulomas of all 33: cases of chronic beryllium nickel-cadmium batteries, arid in electroplating and-- dis6akWah'd in none of,30 cases of.sarcoidosis.*48 It plating of automobile parts and musical'mstiumente. shoul&fre noted that it demonstrated beryllium in the Additional sources of exposure include various dustT&ibhs of coal; workers. Its disadvantages' are welding processes and the smelting ofzinc; lead, and that tEe^echnique is ayadabie in few centers and it copper pros that contain cadiniiim: Cigarettes, may. provides qualitati.ve.andnot quantitative data. Other . contain^.appreciable 'qumtitiits-of cadtniiun';:.!^i.e-/ techniques for the Idetectipn of.beiylKuin'in: tissues forms pf-lxing (^seas'e.hafre been associated,with cad- . uive used electron .microscopy and' have included mium exposure; diffuse alveolar damage, (acute,cad- . ion miCroprobe mass, spectoraetry 'and, electron nuumpneumpnitisj, emphysema, and cancer.t.' ' energymass'spectometry.;>:i ^ .. . ' Inhalation. of .largd'hmbuiits -of cadinium.fume-; Iffias been-postulat.e.d that chronic betylliosis is (usually.the .oxide) 'cani;ause "di&isS''-ahr^jlaa:::d9ia^' caused. by imnitmopathologic mechanispis because age, sometimes' Wstopahoiogic.feai^'eVare similar'ttfiKfiuse-Inlyeq-!;. presence of manifestations of delayed (type 4] hyper iar . damage caused by other agents.. ^Diagnosis. sensitivity.' The latter can be useful in diagnosis. depends on thevMstory of exposure and mineral qe^IIium patdh'festing-o,n. the;s.|in of.subjects with analysis of theiung-tissues. ~ - '.. suspected berylliosis has h^en,di?continned because The ly^.-.b.etweeir chronic cadmium exposure of its unreliability and possible exacerbation of the and;the dqvpiqpftfeniVbf'''centriibbuiar' emphysema disease. However, in vitro transformation tests to was first-notedih the 1950s, but the results of subse beryllium on peripheral blood and bronchoalveolar quent.Spidemiqldgic -surveys have been .ephtroyer^ lavage;-lymph,ocytes_has;beeii positive in nearly all sial., Tbisds because.the'majonty did not cbas.idb? subjects wtbchromqeryifrds^ tesfed.i49r*** It can various.,.c.Qiifditndyig'. factors particularly .cigarette, .alsd-be used for screening of workers but there is still smoking. Howeyer,.a- recent well-condudt'ed study of debate 'as to whether a .pqgijiVe'heiyllium lympho-- a xs.hort.'pf .workers from a copper-cadmiumI'allpy .yte'testin pm:asymptomhtic,workerregresehts latent fectogr . reported! decremehts of luxig fruffetibn- and diseases' : - radiologiG .changes consisfe'at with -emphysema;.!^ <i j '.'Z/A ?y' 'TABLE 15-8.-.:,... . Comparisonof ChrbzucBerylliosis (CS}with ;Sxitc6idosis.(SAM)cCi^pjuc Extrinsic Mlergic^ [ MveoMs fEAA] ', and. Cryptogenic Fibrosing . "'I'/Uv&oiiiis-fCFA) ... ' ' '.Feature, .'' r' CB SAR EAA CFA Exposure to beryllium . Yes No No No Kveins test. Serum precipitins - . Nag Neg Pos Neg Neg' Neg Pos : Neg Predominant distribution Upper Upp^r Upper Lower ; of fibrosis - . .. ' Compact granulomas .. ++ t. + + ' . 0 Interstitial inflammation ;.++ -J- ++ Hilar lyinphadenopathy, . Rare +.+ . 0 0 Note; *. mild/moderate: ++, prominent. HWBUI0009236 488 SPENCER'S PATHOLOGY OF THE LUNG Furthermore, the decrements of lung function of.tungsten carbide,139"161 The finished product con increased with cumulative exposure to cadmium. tains .between 5 and 25 percent of cobait, which is . Inhalation of cadmium chloride by rats has led to thought to be the. agent responsible for the disease. . emphysema.154 : ,? Machine tools requiring vety hard. textured Several epidemiologic studies of cadmium' metal are made by blending tungsten and carbon and exposed workers have reported increased numbers of heating them to form tungsten carbide. Cobalt and..- lung cancers. However, recent information has cast other metals, such as tit'ahiixiii, tantalum, chromium, doubt on its role in causing lung cancer because two major confqunders---smoking and arsenic' 'expo-, surerrrwere. not.controlled for.119 molybdenum, vanadium, hidbium, and nickel, are thenpadded, according to the desired properties, and then sintered info the harcTmetal. ! ; Chromium, . '' ' ' .c ; Exposure to hard mefdl hasheeh associated with ;. diffuse interstitial fibrosis',"'deSqumnative interstitial . Alloys and compounds of chromium' Have been in : pneumonia (DIPJ,;glaiit cell- mtef$tifial-pneumonia. commercial..use foroyer a,century,. Chromium is .a (GIFfSj.hypfrsehsitiyifir pneufiiomtis,.and industrial. cies. There-.are. divalent (e g,, chroxnous chloride (Fig: i5;34). GrGy, bivalent (e.g-i.-dwomighhioride CrCl3), and- cells , may be. found in the bronchoalveolar lavage hexdvaleat compounds. (eTg./'pbtassium chromate , K2CcQ<i) compounds. Experimental andhumanstudw ies `indicate -that ,;the .hexavalent compounds are. pathogenic, -particularly, the relatively insoluble:forms such as calcium, lead, strontium, and zinc, chromates, but also soluble forms. ' "Occupational -exposure to 'dbromium-: cdfflpounds, can .occur ;in a,number ofsituations (Table 15-9)-and can cause perforation of the tiashl septum and an-increased risk of nasal and'luhg;cancer5?? fluid.183 When ah'interstitial disorder is caused by hard metal exposure, analysis Ofthe lung tissues consistentijCj reveals tungsten hut not i.always cobalt, bg^ay^o.f its kolubtiity/Experimenthhstudies have. . indicated thaTcbphlt is respofisibleifor the interstitial diseases, A similar disease has been reported |n dia mond polishers`exposed to cobalt, but not to hard metaj,185 In (tiard :metal;asthma evidence indicates that sensitivity, to BothTcribait and- nickel may be involved.184 These'have; been observed in chromium plating, chidmats production, and chromate' pigment pro Iron . duction- and-flhe risk increases with 'duration and Exposure to < se'verity.of.e^ppsure.!*6"138 The occurrence-of nasal, of.irpn oxide causes little damage' to the limg because perforation-in a cohort qf workers does not -htiOessar?; the.'particle? .jure .weakly fibrogerrici The chest radio ily indicate, that they.have been exposed fo'hrpes and: . graphs may. shosV opacities, but there is usually little amounts of-chromium compounds capable .'of .pto- ' functional impairment! In cases whore exposure has during lung cancers. been heavy and deposits of iron particles marked, the Cobalt--Hard Metal Lung will appear reddish brown or brick red on gross examination (Fig. 13-35). Ferruginous bodies con- Hard metal (timgsten carbide) is a synthetic tungsten .. taining black cores are frequently present, which alloy used in machine tools. Pneumoconiosis has should not be mistaken for asbestos bodies, been associated with the manufacture-, and grinding htficrosebpically, there - will be collections of dark ;n brown; ' dust-Saide.n-: maqrqphages with relatively slight fibrosis; (sidirosis),>jhis may occur in silver TABLE 15-9 , Exposures to Chromium Compounds polishers, ocher workere; anti arc welders. The latter .' may experience exposure" to a variety of other min. . .eral particles and may show a variety of pathologies Production of chromates and pigments (vide infra). Chromium plating .. In some' situations exposure to significant Production, welding, cutting, and grinding of chromium amounts of silica also will occur,108 for example, in alloys hematite miners, foundry workers, and boiler scalers. Leather tanning The lung- will reflect the effects of both silica and Spray painting `iron--so-called, siiicosiderosis. Simple and compli- Steel smelting and welding . ' hated pneumoconiosis can develop in these workers. i; HWBUI0009237 which will be sixoilar to silicosis, or mixed dust fibrosisdependingvoQ-liie amount dfsilicajiresent-67 A high prevalence pf,lun'cincir'has-been reported in the hematite miners fro# Cumberland, which is probably due to high levels of radon in the .vines. Welding is the process of joining two materials by fusion or coalescence under.conditions- of.pres? sure-.and.ternperature. Thirdare xnahy.differendt3tp.es of welding.processes and workers;wiil-be bjgjpsed to a-wide.yariety of airborne particulates dependingfon the.process and-other operations in the facility. Tfa,e welding fumes, will fee contributed'to by: {ljyapor- Izatioa-of the wire.rod.brmetaliic/allojriiigcoatmgs-; (2) decomposition and vaporization oftBMluxmate? rials; (3) spatter from the arc fegidniand-weld-pool . and fumes therefrom; and (4)^vi.pbrization-;hf;,the r' -molten..weld metri.r*f. Welding fumes dan comprise metal oxides such as" iron, titanium,,; chromituri, nickel, manganese, copper, zinc, and aluminum, organic materials, and crystalline materials such as r. - ' silica' and silicates... Welders -can be exposed to asbestos. The lung's reaction to welding wUi^here- fore depend on the gomporitipn of &e'fum&s1aiid:.the cumulative pxposui'e. Weiders^liings typiciS^ show. large, collections of dark brown .spherical^-particles . .. (iron oxide} and ferruginous bodies but little fibrosis CFigs...l5?3.^and%5-37).,Hdwever, a variety.of patho-. i - .V V- logictfesponk^^have been described-in the iuiigfs.of v;-.. on" the type of exposure arid it isir;: .sH0ul4.Be. realized,.that there is no such entity.as : .' . ^"7 Nickel '. .".-'v.;... SEL ". .Alloys and compounds of nickel Have been in com- , }.' overa-cejhfuiy. Exposure to metallic ` ''GURE1S-3S tic lung from a subject who had heed axposed to others for <nany years showing a diffuse reddish brown appearance and multiple stellate gray-brown lesions. (See also Color Plate 4.) : mdkel-compounds in the forms oPfuines and dusts ; can occur in nickel mining; refining, caldiniitg, smelting, and electrolysis and in the production of nickel alloys. It has been known for a long time, that a 489 HWBUI0009238 LungiJroni ta-aic.wslde? shows'coUec- . Uaas ofditjaden'inacKlphagas with lit. - tig fibtmis.,CtoW ppwet.) high incidence of nasal and lung cancer has been asrsociatedi.;with3exppsiires;to nickel during refining and these have.becoine prgscriBeddiseases"Workers involved;in nickel mimiig and smelting have not exhibited the same ievels .of iting and nasal -cancer risk as'those in repneries.Nd excess risk of-these can cersJiaS been found among men Working in nickel alloy^production.,. -However, isecause' the- majority Of epidemiologic 'studies have lacked-details- of amounts and typgs^ofnickbl compounds to which the workers have.be.en exposed, it is not known precisely -whiph-jaickel forms .are. carcinogenic.188 No particu lar histologic type:' is .specific to nickel exposure although squamous are the most frequent lung carci nomas. Acute .heavy .exposures to nickel-have, caused diffuse ..alveolar "damage: Exposure to nickel may cause .occupatiqpabasthnia. Tin A pneumoconiosis can result from the inhalation of tin dioxide (stannosis). This occurs principally among those who bag and sample the cassiterite or who smelt ah^;rf|h^#ie,pr^'|m.d metd. Tin dioxide ores (cassiterite) are mined in GomwSl, Great 490 HWBUI0009239 Chapter IS / Occupational Lang Disease 491 Britain, and Bolivia and those who mine the ore are tery in 2500 b.c. The Romans knew of its fire-resistant also exposed -to, substantial amounts of silica; properties. Asbestos has been, referred to. by. Marco Therefore, in tin miners the major problem is sili'co- Polo in the thirteenth century'and by Benjamin sts and silicotuberculosis although in Cornwall the Franklin in the early - eighteenth century.173 It has incidence has declined considerably since 1950.189 . been present ubiquitously in the environment for Stannosis, Which1 is caused, by exposure.,to. tin-, greater than 10,000. years since it has been demon- perse, is characterized; by striking radiologic qpaci-. stated in Antarctic ice samples.174 However, the *:->s because tinhasa 'high,atqjnic.ttumber. However, major industrial exploitation of asbestos began in the. subject is usually well and shows.little impair- 1870s when large deposits were found in Quebec ment1 in lung function.?r,,. ., ' .!*(chrysotile) followed by Russia (chrysotile) and Macroscopically, the -lungs contain numerous South Africa (crocidolite and amosite). The' pro'diic- gray-black raacides up to about Sjtnm in diameteh " tion and uses of asbestos, throughout the Wtirld Have Microscopically, the macules, are ei^aracterized increased from about SO tons year in 1877 to a peak Of: by numerous dustdaden:taacrap.ha'ges. asidciated;; nearly 8 million tons in the mid-1970s followed by a with littleifany fibrosis.17 PWEF does not occur.The reduction to about 4 million tons1 in the-1980s.tit, particles afe:str0ttgly birofringent The dust'content should be realized that everyone is exposed] to a lows ,i indUriduM luiigs,-can-reach 3 g .tin dioxide; background level of asbestos and themonnal lung Microprobe analysis ofthe ti.ssp.es will reveal the to. contains a low levelof asbestos fibers. . Air inreased -risk dfoltag cancer has Seen, Asbestos minerals comprise two separate niiner- reportedto' Cornish tin miners but this,was probably alogic groups: serpentine, the only member of which due to radonexposure.17t>.- - is chrysotile (white) asbestos, and the amphiboles, Tilaniurri which'comprise amosite, crocidolite, anjhophyllite, tremblite; and. aetmolite., The major .commiraal Titanium dioxide is a white powdermsed in the,-dye :;sdustry, .During the grinding-of fitanium dioxide, dust particles witMiT.'the range tk to T.0 fax are released and can bejuihale'd intoihedung. It is a very, inert,dust and m^niiifalsTtis sometimes used as a negative control for inhalation studies. lo and .asso ciates171 stndied 'thie lung'tissues-froth three factory workers employed In pirocelsing 'titanium ..dioxide pigments and found collections ofmacrophages con taining black pfoticles.These -wife situated around . i hu brohchovascuiar bundles and in subpleurai areas. The particles were birefringbnt when viewed with polarizetiligM There was tittle-fibrosis, . - , . A granulomatous pneumonitis has been described rarely in assbriation'with titanium.expo sure.172. " - '*_ forms have been chrysotile. (90. to 95 percent)'arid- crocidolite and amosite'(5 percent). ' " Individual ehrysotfie fibers, pxe.pliable end curly with -diameters-' averaging O',06. 'joLtn.. Arriphibple' fibers, on the other hand, are straight, rigid andfooie; brittle structures. The. .-finest .diameter airipMhble fibers ori: average are crocidolite followed amb^itefand the thickest.are tafoophyiiite,Tpesmpkte straws-' die greatest-variation being-.reiatiyely thfok'Iri s'birie locations-'(big,; California and Greenland).hnd'foin:ih'; ofoets (etg.. South Korea).17 The,physicd-loimi:of the-fibers are important in their relative patogenic-1 ity. The'difference, in. chemistries .between the .fibers1 allows them- to.be readily identified in'aixborfie'aifd tissue'samples by modern analytical transmission' electron. microscopy... Exposure to asbestos, can occur in a variety'of ASBESTOS V..- ways; broadly classified-: by Zielhiiis177 info'difebt, indirect (bystander), paxaoccupational fog., houses wives washing their husbands' contaminated:'work Asbestos minerals axe agroup of naturally occurring clothes), neighborhood (living, in the vicinity of fibrous silicates that pbssaSs good thermal, acoustic, asbestos mines, dumps,or factories), and ambient(in arid electrical insulating properties; they have flexi buildings where there are asbestos-contaihihg mate bility and high tensile strength and axe stable in alka: rials). Table. 15-ilO gives a list of sources of exposure. line and acid environments. Their use has been The level and size distribution of airborne fibers widespread and they have been incorporated into at these industrial sites will vary according to the several thousand diffefent.iproducts,- .-including tex- ' amount of asbestos used, the manipulation processes '.iies, insulation products; cement, reinforced, plas (e.g.,: sawing;- grinding, milling), and fiber type arid tics, friction materials, filters;-floor tiles, and paints. this will determine the. risk of disease, it is generally In fact, their use goes back several thousand years. accepted that exposure to amphiboles is far more They were used in the manufacture of Finnish pot- dangerous than chrysotile. This is because there is a HWBUI0009240 - m -tum 492 SPENCER'S PATHOLOGY OF THE LUNG TABLE I 10 Exposures to Asbestos Materials worth making one very important point--exposures necessary to produce the pleural complications are Mining and milling of asbestos Insulation work , Production of cement and cement products Friction products far less than those required to produce asbestosis and lung cancer,,probably one to two order's of magnitude difference. ' :. . y. . - '. Shipbuilding . ... Asbestosis (Including. Airways Disease); Textiles ; filters' .. Electrical work ' ' ^> ' v. - ; . Asbestosis is defined'as diffuse * interstitial pul monary fibrpSi's causedfiy'asb.eStos 'exposure and the term should never be used for any pleural changes. Construction; work " -/ The first histologically confirmed case-was described Railway work ,- . Power;statioos . . ... -I:- . - &6n'ahds'teeiip.dustry, . . ' "" G^masfcproductipn ParaoccdpStionaidfamiiyJjexppsure' -Ur : *' Neighborhood exposure--rliying near asbestos factories 'orduinps--. ' in Great Britain. by Murrhy ini t907-b.ut it .was not until 1924 that Cooke proposed the term "asbestosis" and published a detailed-description of the disease. Following the report by MerewetJae'rand Price, in 193Qt8 asbestosis.was officially -reengnized, in. the ..United Kingdom and included within.the,provisions of ffie Workmen's Compensation-. Acts, and ..the Asbestos .Industry Regulations .were - formulated. , Over the decades theseibguiations have becqme pro gressively ` more stringent*.1' so;thatexposes . ' .: ffiffer.dnfial jate of clearance-from thedungs .between. to asbestos have decreased from', .-vvellin, .excess of dv^sptUetaad dfepttibqSes andlt appears that ibis the 100 f/mL before the 1930s to about 1 frmL in 1986.1" retained fiber burden Within the- lungs that is an The Merewether and Price study was of heavily . important determinant of ffiseasgi.Rapid.ciearance of exposed asbestos textile -workers whp showed a very ' cbty^ptile frorii'&rluHg has been shovmfrpthin ani- high-inoidencenflung fibrosis. Withsymptoms devei- v. ma^san'd'human bfeiiigs.17?7*?;Even with continuing opihg'as earlyas? years after sfajffingWqik'and death . high.;jexp.osufe.tp^i^ysbtile steady state is reached occurring- within:,-12..years. Miffi'- feHutlion .in air- ' aftqr ,ab.b.ut 3 :xni6'nmis anththe-'-ievel within tiie lung borne-' fiber levels, in.Jhe wor^lace.th'e disease has remains .'.consta^t^' whereas amphiboles-. are less- become less frequent, and dess severe'. . Asbestosis is rap^y.reijioybd ahtf tehd'to accumulate over-time if usually seen after prolonged substanfikldlrecfexpo there .is cpnUhi^g 'e^qs'ure and this increased level persists afier cbbsktibn. The half-life ofamphiboles. ini the humanJiMg 'is'nieasured in-decades. The .clears sure:ati.d the latency, from firrt.exposure to clinical pneumoconiosis usually exceeds ; 20'years/-Thd'' prevalence of asbestosis is .aksodiafeji^iwifiir^dgei.. ance.'fafeldf fibers is also irifi'uenced by .their- length: short ^bers are cleared efficiently whereas'JLqng fibers (> io ^mT are hot:'Therefore,' with -increasing, time cumulative exposure, fiber.fype, aridsindffitig.190^1-- Clinically asbestosis may be, associated':' with;dys-: pnea, nonproductive cough/ and`basal'braqkles 6n following cessation of exposure the relative propor auscultation. In; advanced 'dikea^jfedl'drSiibbftig; - tion of.long-fibers retained increases.183'14 .Animal cyanosis, and tachypnea may, be present. However, inhaiatian.sthdies.ysmg short-fiber.preparations of many patients are asymptomatic. ' asbestos and eriomfe produced little or no-gispase, Small irregular opacities are the radiologic hall whereas.long-fiber preparations produced fibrosis mark of asbestosis although they are not specific. In and tumors.183'189 Fiber clearance may also be inhlb- particular the milder grades can be caused by smok ited, by the-concomitant exposure to other dusts such ing per se.193194 Pathologic examination of the Kings' as quartz, Ind titahiiffii1^ andicigarette smoke.188 No iday reveal asbestosis.when it is radiqlogicaiiy unde studies of exposure to asbestos in human beings have tectable. Severe degrees of.asbestosis mqyTefuit, ip a, examined , the . possible-potentiating role of other honeycomb appearance although nowadays this, is dusts, in the disease-causing potential. uncommon. Pleural abnormalities such as plaque? or ...Exposure- to asbestos may cause lung fibrosis diffuse thickening may also be present. It has been (asbe.stqsisj, lung'Cancer, rounded atelectasis, pari claimed Chat computed tomography is more sensitive etal pleural' plaques', Miffuse p.leural fibrosis, benign and specific for the recognition-of asb.estos'ts.. ,(bht pleural effusion, and mesothelioma;. The pleural this has' hot been validated by histopathologic stud- lesions will be described in Chap. 34. However,, it is ies of large series of cases. . . . ..... ; 4 s Y. y HWBUI0009241 The alterations in lung function in asbestosis are those found in restrictive forms of lung disease--a reduced vital capacity and reduced diffusion capac ity for carbon dioxide. With progression the total lung capacity decreases.. i*v ikv IN. i c--l; ;. ? macroscopic hi-ti asbestosis is present there is frequently fibrotic iiuckening of the parietal and visceral pleura. In severe cases the lungs may be encased in a thick and often calcified covering of dense hyaline fibrous, tis sue. Parietal pleural plaques may be' present. However, there is no correlation-between the pres- ence.pe ektent of pleuralchange arid the presence or- extent of pafenciiyxhal ahiiorinadities. In severe eases . >fasbestosis, if there is little drno pleural thickening, pleural surfaces will appear bosselated. The lungs are reduced in si2e and show honeycomb changes, which are most marked in the lower and subpleuM/bases: ftrlesser..duress.of asbestosis the lungs may just feel indurated hor. normal, but on ' rnicroscapiciexamipations cpitsiderabie .fibrosis, will be observed;-Ah, the earliest stage, the fibrosis is observed as fine gray irregular streaks but with pro- . ivssipjq they become.thicker.and are. associated with fibrocystic spaces (Fig. 15-38);'Typically the changes;- . are greatest,in the lower zones b'UE occasionally this is reversed.' Because' `iriariy of "these- subjects smoke, emphysema, may also b'e'piteserit. -This disease -will;: counteract'the tendencyYOr shrinkage, of-'the, lungs and will be associated with an obstructive profile on lung function. It may. be extremely difficult to assess 'Sir; precise implications of asbestosis and emphy- FIGURE 15-38 ....... . Luagshows extensive honeycomb change with a peripheral car cinoma in the tipper part of the lower lobe. . . i.nia to impairment of lung function and clinical dis ability .and .will require extensive sampling of the lung for microscopic evaluation. septa. With.furtherprogression there is linkingup,ky MICROSCOPIC fibrosis of alveolar wails of adjacent reipiretpry broh?;' chioles* (Figs. 15-39 to 15-4.2}.- ObUteratibn'of ^Lvejpli; Careful sampling of the lungs is necessary to diag alveolar ducts, and.respkatp^--bf*paclubles;by ;fibrb.:i;XT' nose and assess the severity of asbestosis. If a tumor sis then, occurs, whidh leads to dilatation of.the.reeid-^y^j; present the assessment should be on tissue away _ .. ..uai_ structures-^--so-called honeycomb change;'The the tumor and preferably on the contralateral-* residual cystic spaces,, which may measure .up. to 1.5 side because tumors can result in local fibrosis. cih, may become dined on their- .Inteimal'surfaces Tissue samples should be taken from the apex of the by hyperplastic, cubbidal, or Columnar epithelium, upper lobe, apex of lower lobe, and basal segments sometimes containing -mucous cells. Squamous and major bronchus to include nodes.17 .but somb .metaplasia may also occur; Cytoplasmic eosinophilic authors have recommended as many as. 15 blocks hyaline bodies, similar to the Mallory's' hyaline from each lung in cases suspected of asbestos-related observed in liver cells, has-been observed in approx disease.198 The earliest changes are seen, in ;Snd imately 7 percent of cases of asbestosis.137 The fibro :round the respiratory bronchioles with-fibrosis, of sis is not uniformly distributed through the lung, the their walls. The next stage is extension proximally in the walls of the,terminal bronchibles and distally in most extensive changes being seen in the lower.lobes and subpleural area. However, with progression the , the walls of the alveolar ducts and adjacent alveolar microscopic changes will also be observed in' the-. 493 HWBUI0009242 K ' 'FiGURUlS-39 x y-...yr X i'Slight fibrosis afld;diist accumulation .., ..around a respiratory brancliwle^grade ''{LowjjoWer.j..... " t-' f ,..... $imple^^i^.i^^^^ciA^^lc^exanftilaatibn. - 'piralo^ljrsneltiolBsv^ Grade 3'' 'FibrosisYthat-links iipadjab'e'nK-Eesgiratorjii/- ; ' bronchioles -and*with little Jardiitectural i..-" -/ distortion"'''' 'i-'-i?-!W:- '* w*--*: ;^c-- '.^c-jatoaru .. .. bpaeyctebmg^.;';" ; f:. \, 494 o HGUREJS-40; ...... ,. ; Slight fibrosis around a respiratory brori- . cniole with extension into adjacent aiveo lar waiis'^igrade 2. (Low power.) HWBUI0009243 ;.:hgure is-ir... /Interstitial fibrosis linteiigaipi-adfaSen!! idpbules but vrith Utas $rm'?.eetiirai dis- J J tortton--^de3X{t^w^owac). *>. - : \ possess a clear fibrous core. They are coated with an They can be located within the alveolar spaces, or iron-protein.--mucopolysaccharide substance and interstitium and in cases of moderate to severe appear as golden brown, beaded, dumbbell or drum . asbestosis are usually easily found. When they .are stick structures {Figs. iS-43 to 15-43). They show- not easily found it is usual that the fibrosis has not positivity with Prussian blue stain because of the been caused by asbestos exposure; it is uncommon in iron presen$.\TMs/ca b.e used as a screening proce- my experience to demonstrate a very high asbestos, fiber lung burden by mineral analysis in such cases. . %y- /;' 3n:..PTinstances-^nly. a mindri^ of length. j5ffeatl^si-rriieS^.t^|9e ta|en & identifying5?, fib:eiii4c0me^fii{ed^fdm-fio'^ip;'il5^'8);pxLd them; it is the -&pfe:i^at:is mTgpiftmt and it is charac* terized a;fr^p^enii: fibMii|s^iB'eaxaiice. There are Ott^r'y taken 1 'k lit Ilf mir. ger :fteCk^r.rjB8?faye^.d to becompipior^ ea|'Uy:pbatdd:;'&aii:Mbrter thbmfer ones and ampfrir ; s- ' Ji-v -;i: < 1 s.T>'.'-".-. 3s~ Hfe.il-.-. ..-v i'>*v. .,`5'Vid . - ,Y- fiGURH 15-42.].'- '' Savare ints'rstidai fibrosis with architectural distortion--grade 4 lesion. (Low power.} 495 HWBUI0009244 FIGURE 15-^ Fit, is-43 showing numerous asbestos bodies. (Medium power.* Same case as in Fig- 4*36 HWBUI0009245 boles more, easily -than .chrysolite- Subjects With, a within the fibrous tissue2? aid pulmonary blue bod-'. highrfron oxide content in. their limgs, for example, welders, and.steel workers, tend to fojto femigmoUs Some authors. haye.-ag^e^;tiiat peribroncMoIar bodies more easily both oft asbestos'fibers and other fibrosis .'associated, ^jhte^heslps bodies |i.e;; '^ada 1 mineral particles.19 In these.subjects great care has asbestos) should not be called asbestosis but'-'teain^' to be taken in evaluating lung fibrosis in relation to era! dust mining disease."20? TMs is largely a nsitter Tuginous-body content because many of the.ferru of semantics. .However, it should .be 'realized' that ginous bodies will not be formed on. asbestos; One peribronchiolar;.fibrosis,' te In.' the 'iuiigsrd.f cite aisotese a.grading scheme for asbestos bodies.*03 rouUnely autopsied,subjeQte.m:`^d.ihno.igXp.9ffl2re'tb/ This shows ar;good correlation jvith asbestos fiber asbestos has oecimeti-,mdtiiinosj'j:ases'-is relafid' tci level determined microanalytictdly and extent of cigmette'tenokingi Secondly .a ^variety of other nifited fibrosis. Other features that may be seeh in cases of dusts including silidd, cpd'djastj-fioa.qxide^apd alii-' asbestosis are foreign body giant cells, often located minum oxide can be, assoqiatea With similar .changes;- around the asbestos bodies, osseous metaplasia Mineral analysis is required in this situation to assess : i the relationship: to asbestos. However, these .changes .i [y <011 th'eir;0wn=gce-jmdi}caly.to b]g.q{great. functionalsig" rufic^^aj^^^eyr^ruiiBlgly to be progressiW? urdetef&eJtehestos fibertoad within the luhgte gfat enough to fcapse such changes' > OlFreRENTiALDfAGNOS.'S The maa^ppih^fi^c^gs.cbpic.Changes^&K the lur^s'dife'i's.ifiul'j|r-'wb6m':.i3i|^a^i^|?ulm1^^ fibrqsirmd'a^ r.'tftdnerpus' a . v-asbestos- Ebfehloid;;Fieuihl .thi'ckemng and glaques .'sbr.ebnore/'common'infcasds of^H#si6iisS:&gwpii)'ep;. FIGURE tS-46 ' ... Electron microscopic appearance of naked amphiboie fibers ana asbestos bodies. exposure .than visibes'tbsis<;?Giases!iqf idibpaflaiQ 'pul- / mbnaryifihrosis .caii'occt&.ihb^bjects withasbestos exposure,**?? aid they may^StfS^W pleuraLcliati'ges ' but examination of the lung tissues.Willisyeal sc.fnt or;absent asbestos bodies. Minfitedbgic';teialyste'fif thdse cases is - useful in demonstrating a' relatively low fiber level. '' - 497 HWBUI0009246 498 SPENCER'S PATHOLOGY OF THE LUNG The diagnosis of asbestosis should not be made lungs whether determined by asbestos body content on small biopsies because they are frequently unrep ..-qrmineralogically.:: ' resentative. Also if a tumor-is present in the lung, fibrotic changes in the vicinity should not be byerm-.., Asbestos-Related Lung Cancer terpreted because tumors frequently result m fibrotic, ; : - Thelink between lung cancer and asbestos exposure changes per se. If one is dealing with a postmortem^ ' was first'estafilished by the systematic epidemiologic case the assessment of fibrosis is best performed, on: .studies.ofDqlI2f :and^res|owz09.published in 1955. tissue specimens obtained from the. riontumorpp;s . - In 1979, Hahnxion.d andcqlfeagues published a study lung- . ;. -. - Jf: V. examihing.the effects of smqlaBg and asbestos expo- Sarcoidosis, extrinsic allergic alveolitis, anffEis- x sure and .the;iis!k:of the!'idvelopinerU of lung can- tiocytosis X also have to be distiriguishei/from;.,, cerl2W They Mmd that lie effect of .smoking and asbestosis. They tend to show a greater :ppperzqu#i- ashestos exposure qn the risk oflungcancer was mul- distribution of fibrosis although there-ars;exceptions1-; yfiplic'ative. It should-be realized, however, that this to this. The demonstration of granulomas or foci qf xis|c; was applicable" to a heavily exposed group of histiocytosis-Xri-will exclude asbestosis.. If there, are' .insulation.'workers, nearly all of whom.had asbesto- any doubts mioeralogic analysis.will be fielpfite -' ...;.sis211 and should not be. applied to all other groups of Other mineral dusts including talc, mica, kaolin, " asbestos-exposed Workers: The -excess lung cancer and hard metals can result in interstitial fibrosis. risk was much less in other cohorts add varied with Lungfjbros.is induced by nopfibrous silicates is asso industrial process, being relatively high in textile ciated with extremelyheavy mineral burdens,2-3 and workers. anfi. very, low in friction products and there ..should be a good history of exposure and asb.estos cement mantifacturing?12' In somelgroups numerous easiiyiddn&edrjmiieiral partides, within the risk.was'betiyeeh'adchtiva &d ritiltiplicative^,3: . the Irmg.".h'iiaeral a^^^esm^lielpful-in-this.-skti* It..is- rare, m jabseiye ahmg'haiiceir m.-a'h'onsmbking atioDL.. ..... ' ' " " '2-' ` .1- .. Hammar has reported focal ossification in about onerthird qf, cdses of:grade 4-fsevere) asbestosis20; individuad..expqsed to'asbebfos;-y;:.:,V'''''?-; ?' vC The-risk of. lung cancer ^so varies ;with;^fiber type; consistendy Idwerrates occur & occupMonal. and has. MpUedJ that it is helpful1 in distinguishing cohprts e^p|ed to -chiysdtiie relative .to ...similar asbestosis from ihterstitial pulmonary fibrosis (Fig.. cohorts. .espied:' to^amphibolfes: '-For' example,,, the; 15-47). However, this featufeunay be'seen in intersti staqdmd mortality rate for':luhg:Cah'def:for.<fi^?otd^ - tial pulmonary fibrosis ind the inpsf reliable diag mining and. milling is 125'whefeas Tor amghibple' nostic indicatgr is a Hlgh'leVel ofiasb'estos within the mining and milling it is 264.2i3`;'' > i >'! ) HWBUI0009247 Chapter. 13 / Occupational Lung Disease 499 The latent period from the first exposure to TABLi-lSri 1 . asbestos arid the development of an asbestos-related Commonly Used Inorganic Nonasbestos lung cancer is usually in excess of 20 yearsand usu Mineral Fibers, . .. ally requires prolonged heavy direct exposure. Chiirg reviewed the literature pertaining to lung cancer type and .asbestos exposure and'found that ail the major histologic types occurred.**5 However, there are sev- rr|| limitations to this kind of-analysis, hr many .. there, has been no attempt to separate within Natural. Sepiolite Attapulgite/palygorskite Wollastonite Zeolite Synthetic Mullite Glass ' Wool Fiber '. ; tiie pphorts those tumors that are related to asbestos Continuous filairient exposure and those that are not. Similarly . little {yliaeral wools attempt was made to control for corifounders such as sex and year of diagnosis. A study by Johansson and associates,*16 which controlled for these., factors, found that there was an, association between adeno i- ............... .. ' ; Rock .. Slag. Ceramic ' carcinoma, of the lung arid a peripheral locaKiatipn !.*h asbestos exposufe-. flbwever,'the data are'still nut sufficient to use the histologic type ofcarciriorria In ahasbestos-exp.osed jyorkfr forascriptiotf oraot of dung caacer to asbestos, exposure. ' j y: - There is now reasonable Evidence, to rise the presence-.orabsence.ofjasbes'tbsis as" the'criterion for ascribing a-lung cancer .to asbestos (see' Fig.'l5-38). Epidemiologic . and histopathologic' studies have iisritcated- that lung cancer risk from asbestos expo.irons increased in those industries. where aibestosis occurs, hut not in those'.where'it does' not5'and thatrit Increases with ie.yerity of'Sibestom's:*17'*18 are needed, Environmental exposures tp hripnite fa fibrous-zeqlitej .have been associated with very high rates of mesotfaeMoma and lung cancer in..three yil- lriges -in Turkey.2?ilri-animal ihhh|afibn'studie'&riH-.. toaitrihair produced the highest rate. of meso|belioma from any known fiber. ' " , ' ' The synthetic group includes a variety of differ ent fibers arid. both, workers and-,the gerid^l public haVe been, exposedrio theim^udfite.ffib^'areffre^ l^eri'dy'fcuhd jxi 'the lungs ^f.n^q^alJEztdiy^iiels , Furthermore, the increase appears to develop when there is radiologic evidence of fibrosis,216 and 'this Corresponds to Mftopathqlogic grades, .of 2 or 3 or .greater. Animal studies.iavelshbwn'ri;strong link between the development.of lung fibrosis and tumor ^"illation..*29. ~ TV .. , . . " ' Noriasb.Qstos Fibers ' sil fiielsrmarS4sedriumb&s;aie found in th.e lungs''of' cbildfrad-pawer station, workfus but thgy ho riot appear to have any pathogenetiesignifiemhe. The other fibers are'rarely encountered on. min eral ^analysis:\6f human lungs. -This fis* probably... b'^^tKerjaaiorityere n<j| '.The majority of epidemiologic studies 6f gl&iss .yffibl _r6%^slagfyoolpaa4contiDi!i9Us.;^Um.ent^3fp)dnc`aSji - These 'include natural and ``synthetic .fibers. ..(Table 'WorherirhaW nohshown.ari increased nsjc'hf iulig-.. IS-IU), a proportion of which are respirable and cancbfwriieso'theiibma. A few studies.haveshoiyii' ; therefore potentially pathogenici ffiformation con an- excess of lung cancer in rockwqol ;arid slagW'bpl cerning their health affects is limited hut continued. production' wdrkersbut this has been in .the .workers vig'ilaHce'for possible health effects from exposure to in thhriaHy production phaseajqd.jhe.'siu^g|:`ha:s,e': fibers should be riiairitaiiiedbecause of the long riot been weli'cbafioHedvfor eqafounders puch.es . h.ut periods between first exposure..to. a fiber and smokfhg:ahd asbestgs, In- summary, the. excess'lung the development of pleural and pulmonary disease. cancer mortality found in some production worker's Their rise as asbestos substitutes, particularly the may not necessarily be caused by exposure to air synthetic fibers, has been increasing over recent borne manmade mineral fibers.224-225 years. ...... - There.is. spine concern about refractory.C.ererpic ' The natural group includes sepiolite, attapulgite fibers because'. these are , durable' in lung rtissues. (palygorskite), wollastonite, and. zeolite. The infor Animal inhalation.studies with these fibers1have pro mation on these .fibers is. very limited. Attapulgite duced lung . cancers and., mesotheliomas?229 They . posuxe has been linked to lung cancer221 and wol- have, been produced in limited quantities and only lastdnite, has been associated with pleural plaques represent approximately 1'to 2 percent of world pro and lung fibrosis.222 Further studies of these fibers duction. They have Keen used in paper, boards,:b.lan- HWBUI0009248 3 500 SPENCER'S PATHOLOGY OF THE LUNG kets, 'and heat-resistant linings of furnaces.'No mesotheliomas or lung cancers in humans have been linked to re fractoryceramjc fiber exposure so far,, - : ORGANIC DUST.DISEASE . `' ' `. . r: A simple classification of. organic dust diseases',is shown in Table 15-12. identified in thesubjects. The majority of low molec ular weight compounds. that cause occupational asthma, act through this pathway, for example. iso-cyanates, colophony, and, wood dusts. 2. Nonimmunologic-^rSn this type reexposurelo ' small amounts of the offending agent does hot cause the symptoms. Some may-be due to direct irritant or pharmacologic reactions. . :' OccupafiorialAsfbma ... "Occupational asthma is asthma which is due, in whole or part; to agents encountered at work."**7 Thepathologic changes fbf eadr type of occupa- aortal -asthma have not been well studied but- appear to be similar to-thase of nonoccupational asthma, .. .... ' Lmgely duetto better recognition,, but also due to an Rvssihosis : . ' . *Vu- increased number of chemicals in the workplace; the . :J .... prevalence of occupational asthma has increased. /Byssuxosi^, derived from the Greek work meaning over the last two decades. More than 200 chemical ' flax. is.the tenn appiied to respiratory disease caused agents hay.e.been'itnpiicatedin its causation. Soin.e..of -by the inhalation of cotton dust and now also caused the . most feqhent-are :iisocyanates, aidxy.drides, by.flax.and hemp,3 colophony, metalsVaiaijiial proteins;'wood dusts,..and For over a hundred years if had been recognized grain had flour du'stsV Occupational asthma is. jtiq.w -.tj[iat.spme. of the wgrkers'-ehgaged in the Lancashire the iHffst'^reVai'eiit 'bcCjipationEd-lung disease,;in vG.0tto)aftls;. -c^eyelqpea "a2chest 'disease similar to developed countries.228 ' ' - -- .> cteQnic.bmnclutisi.it'has' afso been reparted. among. .. . There is" a lag -period varying from months to . cotton mill operatives in North-said-South Carolina.- years after starting a job before sympfoms-.cosnmeric.e. . A similar;' iUness has been described-: among: flax ..MtiaOy, symptbiss'pcc'urat wpik&xiimprove jvhen .workers^p Northem Ireiand,23.q'ahd-hethp: workers in the's'ubjpct is away-fooni:-the--5korkpiace.:but; as,.t$e ;.My.ma.Jrtoce.2?*'In the cotton-industry-.it occurs conditionpro'^esse's thVsympfoms may become ftffr- particularly .among those eiriptlbyed; mblowragiand sisten't'and the typical work related pattern lost; .. . cardinglheraw cotton, formerly 'a very dusty process Agents can cause occupational asthma by sev and: the prevalence is increased in cigarette smok- eral mecKahusms.22-9- '- -b: ers.232 - -3,- -.-A ; . , Clinically. dih'condition presents as a.tightness i.Tniinuhoiogic--thzQUgh: an'.immunoglobulin (I^l-dependeht ih'ichaMsm where specific Ig^s..anfi.- , bodies'can'be idhhtiftdd'in thesubjeet. Positive skin tests id tfife antigen maybe present, although.tbese do not always cbin'cide with symptoms and may there fore be a marker of exposure rather than disease-This pfihe. chest, cough; and aithrhatic wheezing, which is most noticeable''when the'operative retums- to- work on Monday after being away from the mill for the weekend. It does not usually develop with less than,20 years of exposure. Roach'abd 'Schilling233 /dimded;jh'eseverityufbyssinqsfo-kifo4^.?llS^f.^- is usuahyinduceclby -high molecular weight compounfes&c&frpjdinil and plant proteins.... ...: ... Through rhdh-^IgBdependent, mechanisms- but probably'involving cell-mediated-immunity. Specific IgE antibodies to-offending , agents axe-not .usually - Grade 0 .- ,~:Symptomless.ph Mondays3 ^ "Grade 1/2/:.ccasipnal-chest tightness.:.oa 'the first - 'r` :'' -working, day; .of..the vveek or. mild symp- 3 -.';;toms-such as.finiationbf the respifijwry. ;: Ttraet;. . ... ' .f ~ TABLE 15-12 3- - Grade-1'' Chest tightness or breathlessness on the ' T--'.T.wErst day of theworMng.week'ohly . ' Classification of Organic Dust Diseases, ''' Gride 2 ' Chest tightness or.breathlessness, on the Allergic Occupational asthma Humidifier fever .- ... Byss'inosis . . _ Hypersensitivity'pneujmoaititis-;''"-- Erst and other days Grade 3.. Chest tightness' or breathlessness accom panied by permanent--respiratory , inca- . . ; gacity from reduced- ventilatory capacity 'Toxic ,- ... Acu|$ organic dust toxic syndrome (mycofoxicosisT .*"-/? Edwards and. cow,orkers23`* studied the lungs from 43 byssinotics and found that the proportions of HWBUI0009249 Chapter 15 ( Occupational Lung Disease 501 mucous gland, muscle, and cartilage were increased REFERENCES in the named bronchi. Emphysema does' not appear to be increased.233 So-ealied byssinosis bodies have been described blit "these are. probjbly. ferruginous l. Parkes WR: Occupational Lung Disorders. 3rd ed. Oxford. Butter.worthrHein.emann,. 1594. bodies formed on carbonaceous material and are.nei 2. Harley. RA Jr. Tobacco, in Daii DH. Hamraar. SP. (eds),. ther specific fdr norfound ih OTOiy ease ofbyssinosis. Pulmonary Pathology, id ed. New York. Springer-Verlag, It will be realized ;from this ,descfiption-that'the pathologic changesare nonspbeifiq aiid the diagriosis ' t.1994. pp 831-84$. ' 3.BrainJDr Valbetf ?Ai Deposition ofaerosol in the respiratory tract Am Rev ResptrDis 120:1325-1373.1979. . . .. :j!* has to be made on clinical grounds... 4.- Tiiubfell Vj.Depositton and retention of fibres in the human j^. Extrinsic Allergic Alveolitis (Hypersensitivity : r'V Pneumonitis) .. ': lung, finn 0&upHygiSM7-369iHm2. . 5. GarrityTR.GantardCSi YeatasQB: Areathemadcainspdelof particle retention iif-tbe airspaces of human lungs. Br.fbtd ,&fediOrlZl^tSO, 198X j ' ' .. .-;*v x - See Chap. 13/ .. 1'... ii' *.TimbraUV...ftopl'pyFQtyiiijpiir ffe 'Characteristics, ofrespirableasbestos fibres,Yn SJuipiro HP ad), Pneumpcpn/oses:' Humidifier Fever ' '. - - ; Subjects exposed to "conditioned'' air contaminated Proceedings ofthe Inteaiatiptial Conference, fahqnnesbmg. . tr5ndon,:<3xfgrd.Uhiy.eis_ity PrSsi, 1970, pp-:l2Grl2S, 7. Dennis WL; The effect oThreadudg rets on the deposition of particles tn;the human respiratory ^system; is Wtftoa WH by, micrqprgamisiiis" such as `bsEfeteria ani-fungi-can. (edj Bdrqlsd Particles JH. vbl. 11 Old Waking,-Unwin ki develop; a condition,called; humidifief-fever^characterized by mild malaise; ievdr,.swskis! cpu^hrbreath- Brothers,l9Zi..ppM~ib^: . . . l' Adutsog, lYR.^.Bowden; DH;' Effects of irradiation on macraphaycrpfpegse.aad'tr&spdrt of partides.acitpss the lesmhs#ran.d-;gerieralized aches/it usually develops alveolar epltheUuhu'r&'yf'iiffti/'iH6:40-i4S;.i982i:.;.;..; oa. the . first day of work afteir a weeiend',or..hp.iiday S. Lee JOB JLung response tq.particulafes with emphasis on.-asbestos \ but resolves spontaneously within a day or two even \ . though there.is^ continued exposure-The pathoiogy v'r andpa&dgenesisofthe co.ndifidQ.ere unknown. The clinical and'laboratory changes aresimilar td those of acute extrinsic allergic alveolitis except, radiblogic . and other-fibrous Sisisi Cni ffevToiaci3Mi:i3~3S, 1985. 10 Pinkerton IQS',. Pratt PC, BrodyAR,-CrapO.JD: Fiber localiza tion and its relatibihhipTo.iungrekctioa'mrats after chronic inhaiatiott:ofchrysofife aiblsMs. Ant/Pathol 117:484-498, 1984.'.;WcF- 11. VincentJib Jones A&Jofi&biiXM,-,MtMiUan C. Bolton RE, changeffiare absent and it does hot progressito.iuag fibrosis. . .... ''' ' Acufo'Organtc'ptisf Toxic Syndrome 7 Cdwie fftiAccumulatspa^bf iphaied raidaHd dust in the lung .. ' .and associatej lymph nqdfesifeplicadohs^^'for.expjosura and dcjM ' ia. jocqnpalittaal'msStSd. *Ann Occup Hyg 31;37S-393,1987. "-r-.-.v- ^ 12; Cohen D, Aral,SF. Brain JD; Smoking impairs long thrift dust <Mycotoxic:oslsiV., ;.';r';r ... This syhdrome'follows'exposufeto very higE'd.&vels - clearance ftom the lung; Science'204t^S14S17,1979,r? ...' 13, McFaddenD. ^rigitJl.i/Wi^s B/GKurgA; SmokingMlihid ' . asbestotijiiua<u. :^qi fit&tiespirDtf333:372t374Z -1.j986. of organic-dpst containing fungal spores and&yphae and it*is: thought,to acf throd^a toxic';rathet than.a hypersensitivity mechamsm!?38'i3!l' It' has been described in'form workerswho have unloade'd'storage sUpsV'cottqn'workers'("mill'fevery)> antli storage 14;-'Mossmaa.BT,$e$p%QtEjfectsof Mineral Dusts on Cells. Berlin, Springer Veriag. f989.;NATQ ASt Series H..Vol 30. IS.- -WagnerJC: Pyerytew df.pxperimeafaf pSsiimbcdnidsis, in CUT (ad); ftfodefs ofLungDiSedie/tiev* York. Marcel.Dekker, 1990, pp-753^7801' -5 10. Gibbs'Aft;, pathological reactions of the lung to ;dust. in elevator workers ("grain feVer-'J.'-Aftar exposure the subject'develops an acute influenza-like illness and craddes are frequently heard oh.ad'icultadb'&;Ehe'st radiographs show diffuse isflltrate^^Tife ."dSease is usually kelf-ihniting although it may persist ,fpf sev Morgan WKC^-SeaWh A Occupational Cung^ Disease. :3dWAPlriladelghia<WB:Sauis^e. 199S; pp.lri-rl??,* . 17. Gibbs ^,f3ea.i^tE:.Examittatlan oflung specimens./Cf/n Patfw/43;S8-72,`1990.' ` 5 r'1-'/- .18 Gibbs AR Pooley FD: Mineral analysis in :lung disorders. 'Thomx{taptetsl.:'7;i' ,L'' ' ' eral days. It shades mahy 'featrtres with acute, farmer's lung and'silo-filler's disease, which is.due to nitrogen dioxide toxicity. ' -.- Few cases have been studied pathologically. 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