Asbestosis is a fibrosing lung disease caused by exposure

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1 Asestos Fier Content of Lungs With Diffuse Interstitil Firosis An Anlyticl Scnning Electron Microscopic Anlysis of 249 Cses Frnk Schneider, MD; Thoms A. Sporn, MD; Victor L. Roggli, MD Context. Asestosis is one of mny forms of diffuse interstitil pulmonry firosis. Its histologic dignosis rests on the pttern of firosis nd the presence of sestos odies y light microscopy in lung iopsies. Ojective. To determine the sestos fier urden in ptients with diffuse pulmonry firosis (DPF) who hd history of sestos exposure, ut whose iopsies did not meet estlished criteri for sestosis, nd compre it with the fier urden in confirmed sestosis cses. Design. Fier urden nlysis ws performed using scnning electron microscopy nd energy-dispersive x-ry nlysis of lung prenchym from 86 ptients with DPF nd 163 ptients with sestosis. The correltion of the numer of sestos fiers found for quntittive degree of firosis ws nlyzed. Results. The firosis scores of the sestosis cses correlted est with the numer of uncoted commercil mphiole fiers. Seven DPF cses fell within the 95% intervl of sestos ody count y light microscopy nd 3 cses within tht of the totl commercil mphiole fier count. Conclusions. Strict histologic criteri re useful for positive identifiction of sestosis mong cses of dvnced pulmonry firosis. Few DPF ptients with history of sestos exposure whose iopsies did not meet the criteri for sestosis my hve sestos fier counts in the rnge seen in sestosis, nd fier type identifiction y scnning electron microscopy with energy-dispersive x-ry nlysis should e considered in these rre instnces to void flse-positive nd flse-negtive dignoses of sestosis. (Arch Pthol L Med. 2010;134: ) Asestosis is firosing lung disese cused y exposure to sestos. The degree of pulmonry firosis is relted to the fier urden in the lung nd the type nd durtion of the exposure. The significnce of individul host fctors remins uncertin. Criteri for the histologic dignosis of sestosis hve een proposed y the Pneumoconiosis Committee of the College of Americn Pthologists (CAP) nd the Ntionl Institute for Occuptionl Sfety nd Helth (NIOSH). 1 The CAP criteri require discrete foci of firosis in the wlls of respirtory ronchioles ssocited with ccumultions of sestos odies in histologicl sections. The former criterion my e difficult to ssess in cses with diffuse firosis nd could overlp with other diseses showing similr chnges, for exmple, respirtory ronchiolitis-ssocited interstitil lung disese or exposure to vrious dusts other thn sestos. The ltter criterion is vgue y not stting miniml numer of sestos odies required. The light microscopic count of sestos odies Accepted for puliction My 22, From the Deprtment of Pthology, Duke University Medicl Center, Durhm, North Crolin. The uthors hve no relevnt finncil interest in the products or compnies descried in this rticle. Presented in prt t the Congress of the Interntionl Acdemy of Pthology, Athens, Greece, Octoer 16, Reprints: Victor L. Roggli, MD, Deprtment of Pthology, Duke University Medicl Center, DUMC 3712, Durhm, NC (e-mil: roggl002@mc.duke.edu). my e surrogte mrker for n individul s exposure nd hs cused some degree of disgreement mong experts. 2,3 Severl studies hve ttempted to distinguish ptients with ckground exposure from those whose exposure ws t or ove the threshold cumultive dose. They found tht 2 sestos odies per squre centimeter correlted with fier urden 40 times tht found in reference popultion nd tht more thn 95% of sestosis cses hd more thn 2 sestos odies per squre centimeter. 3,4 The 1997 Helsinki criteri incorported these findings into more evidence-sed criteri for the dignosis of sestosis, requiring (1) diffuse interstitil firosis nd (2) 2 or more sestos odies within section re of 1 cm 2 or count of uncoted sestos fiers tht flls into the rnge recorded y the sme lortory for sestosis. 5 Histologic grding of sestosis cn e performed ccording to NIOSH scheme tht includes scores for oth severity nd extent of disese. 1 An expert pnel convened y the CAP is currently in the process of updting the sestosis clssifiction scheme nd dignostic criteri, with results expected to e pulished in Occsionlly, one encounters diffuse pulmonry firosis (DPF) in ptients with history of sestos exposure, in whom dignosis of sestosis cnnot e mde due to lck of the chrcteristic firosis pttern or, more commonly, due to the lck of sestos odies in histologic sections. Here we report the results of sestos fier nlysis on 86 such cses. We determined the rnge of sestos fier concentrtions seen in histologiclly confirmed s- Arch Pthol L Med Vol 134, Mrch 2010 Asestos Fier Content Schneider et l 457

2 Tle 1. Grde 0 Grde 1 Grde 2 Grde 3 Grde 4 Grding of Severity of Firosis for Asestosis Cses No pprecile perironchiolr firosis, or less thn hlf of ronchioles involved Firosis confined to the wlls of respirtory ronchioles nd the first djcent tier of djcent lveoli, with involvement of more thn hlf of ll ronchioles on slide Extension of firosis to involve lveolr ducts nd/ or 2 or more tiers of lveoli djcent to the respirtory ronchiole, with spring of t lest some lveoli etween djcent ronchioles Firotic thickening of the wlls of ll lveoli etween t lest 2 djcent respirtory ronchioles Honeycom chnges estosis cses compred with tht in DPF cses for which histologic dignosis of sestosis could not e mde. We ssessed whether the fier concentrtion correltes with the severity of firosis in sestosis, nd whether cses of DPF exist whose fier concentrtions overlp with those seen in sestosis. MATERIALS AND METHODS Cse Selection The study group consisted of 163 cses of sestosis nd 86 DPF cses encountered etween 1982 nd Fier urden nlyses using scnning electron microscopy (SEM) with energydispersive x-ry nlysis hd een performed for ll cses. The dignosis of sestosis ws sed on the criteri previously cited. 1,5 All ptients reported history of sestos exposure, lthough the durtion nd specific source could not e scertined in some. In one cse of sestosis showing n sestos ody count elow the fifth percentile for sestosis cses, fier counts y electron microscopy were not performed. This cse ws excluded from the nlysis. The dignoses for the DPF cses were sed on commonly ccepted criteri such s gross nd microscopic distriution of firosis, presence of firolstic foci, inflmmtion, honeycom chnge, or lveolr filling. 6 Iron stins were performed on some cses of sestosis nd ll cses of DPF to enhnce the detection of sestos odies. No sestos odies were detected y light microscopy in the histologic slides of most DPF cses. Five cses showed rre equivocl frgments of sestos odies, nd 3 dditionl cses showed rre sestos odies fter extensive serch. The ltter 3 cses could rguly meet the criteri for dignosis of sestosis. Approvl from the institutionl review ord ws otined for this study. Grding of Firosis The severity of firosis in the sestosis cses ws grded ccording to simplified version of the CAP-NIOSH grding scheme (Tle 1). 7 If more thn one slide ws exmined, n verge score ws otined for n individul cse y dding the scores for ech slide nd then dividing y the numer of slides exmined. Diffuse pulmonry firosis cses were ssigned firosis score of 3 in the presence of DPF nd firosis score of 4 if honeycom chnges were present. All DPF cses showed firosis t lest s severe s grde 3 sestosis cse. All grding ws performed on thorcoscopiclly otined or lrger tissue smples (loectomy, pneumonectomy, or utopsy). Fier Anlysis Fier nlysis ws performed on lung tissue smples otined either t the time of surgery (wedge iopsy, loectomy, or pneumonectomy) or t utopsy. Most lung smples were formlin fixed, nd few were prffin emedded. For the ltter cses correction fctor (0.7) ws pplied to the finl clcultion so tht the results were comprle to the formlin-fixed tissue results. 8 Lung tissue ws digested using sodium hypochlorite nd the residue collected on filters. 9 Filters were mounted on glss slide (1 3 filters per cse) nd sestos odies counted y light microscopy t 200 mgnifiction. Another filter ws mounted on cron disk with colloidl grphite nd sputter coted with gold or pltinum for exmintion y SEM. Scnning electron microscopy ws performed with JEOL JSM 840 ( ) nd JSM 6400 ( ) scnning electron microscopes (JOEL, Peody, Msschusetts) operted t n ccelerting voltge of 20 kv, screen mgnifiction of 1000, nd scn rte of 10 seconds per frme. Ech field ws scnned t lest twice to serch for fiers. Both coted (sestos ody) nd uncoted fiers 5 m or more in length were counted, with fier defined s minerl prticle with n spect (length to width) rtio of t lest 3:1 nd roughly prllel sides. Only fiers 5 m or longer were counted. A totl of 100 fields (filter re of 2.37 mm 2 ) or 200 fiers, whichever occurred first, were counted for ech smple. Blnk filters were lso exmined nd ll regents were prefiltered to void contmintion with fiers. 9 Sttisticl Anlysis Simple regression nlysis ws performed to correlte the grde of firosis of the sestosis cses with the sestos fier or ody count. Ninety-five percent prediction intervls were constructed for these liner models. Asestos fier concentrtions of DPF cses were sid to fll into the rnge of sestosis cses if they fell into the 95% prediction intervl t their respective firosis score. Anlyses were performed using SttGrphics Centurion XV sttisticl softwre (Sttisticl Grphics Corp, Herndon, Virgini). Sttisticl significnce ws considered for P.05. RESULTS This study expnds the findings in 36 cses of sestosis nd 24 cses of idiopthic pulmonry firosis reported previously. 10 The sestosis group included 3 femle nd 160 mle sujects, rnging in ge from 44 to 91 yers (medin, 66 yers). The durtion of sestos exposure ws ville in 110 cses nd rnged from 4 to 49 yers (medin, 30 yers). For 5 dditionl ptients the durtion of exposure provided ws yers. Of the 163 ptients with sestosis, 74 lso hd mlignnt neoplsm of the lung, 40 hd mlignnt pleurl mesothelioms, 6 hd mlignnt peritonel mesothelioms, nd 4 hd mlignnt tumors of other thn pulmonry or pleurl origin. The DPF group included 6 femle nd 80 mle sujects, rnging in ge from 20 to 91 yers (medin, 63 yers). The durtion of sestos exposure ws ville in 31 cses nd rnged from 2 to 39 yers (medin, 22 yers). For 3 dditionl ptients the durtion of exposure provided ws yers. Twenty-three sujects were smokers, 8 were nonsmokers, nd for 55 no smoking history ws documented. The DPF cses fell into the following dignostic ctegories: usul interstitil pneumoni (77%), nonspecific interstitil pneumoni (6%), desqumtive interstitil pneumoni (4%), polymyositis-ssocited interstitil firosis (1%), nd not further clssified or unclssified firosis (12%). Of the 86 ptients with DPF, 13 lso hd mlignnt neoplsm of the lung, nd 1 hd metsttic disese to the lung from primry tumor elsewhere. The rnges of concentrtion of commercil nd noncommercil mphiole fiers, chrysotile, nonsestos minerl fiers, nd sestos odies detected y light microscopy for the sestosis nd DPF cses re shown in Tle 2. The predominnt fier types found in sestosis were commercil mphioles (mosite nd crocidolite). In 5 sestosis cses the noncommercil mphiole fier urden ws found to e mrkedly higher thn the commercil 458 Arch Pthol L Med Vol 134, Mrch 2010 Asestos Fier Content Schneider et l

3 Tle 2. Cses Asestos nd Nonsestos Fier Concentrtions Detected in Asestosis nd Diffuse Pulmonry Firosis Cses (Coted nd Uncoted) (Uncoted) Noncommercil Amphioles c Chrysotile NAMF Asestos Bodies (y Light Microscopy) d Asestosis (medin, ) (medin, ) (medin, 920) (medin, 910) (medin, 2500) (medin, ) Diffuse pulmonry firosis (medin, 330) (medin, 490) (medin, 490) (medin, 690) (medin, 4400) (medin, 16) Arevition: NAMF, nonsestos minerl fiers. Reported s sestos odies or uncoted fiers 5 m or greter in length per grm of wet lung tissue. mphioles include mosite nd crocidolite. c Noncommercil mphioles include tremolite, ctinolite, nd nthophyllite. d Asestos odies detected on the filter preprtion fter digestion of the lung smple. Tle 3. Cse No. Age, y/sex Fier Burden of the 5 Asestosis Ptients Whose Noncommercil Amphiole Fier Count Ws Higher Thn the Amphiole Fier Count Dignosis (in Addition to Asestosis) Asestos Exposure, Durtion Coted Amphioles Uncoted Amphioles Noncommercil Amphioles Chrysotile NAMF 1 74/M Unilterl diffuse pleurl Mnufctured sestos firosis lnkets nd gskets, 7 y 2 ND/M Necrotizing grnulomtous Lived in Turkey, ND inflmmtion 3 75/M Centriloulr emphysem Anthophyllite cement pipe plnt, 2 y; utomoile industry, 25 y 4 66/M Mlignnt pleurl mesotheliom Plsterer, dry wll, 11 y /M Lung denocrcinom Lived ner vermiculite processing plnt, 20 y Arevitions: NAMF, nonsestos minerl fiers; ND, not documented. Fiers 5 m or greter in length per grm of wet lung tissue. Previously pulished. 22 mphiole fier urden. These cses re summrized in Tle 3. Most DPF cses showed commercil sestos fier concentrtions elow the detection limit. More DPF cses thn sestosis cses were found to contin noncommercil mphiole fiers (tremolite, ctinolite, nd nthophyllite), lthough the sestosis cses tht hrored noncommercil mphioles did so in higher concentrtions. Chrysotile ws found in only 6 of the DPF nd 17 of the sestosis cses. The firosis scores of the sestosis cses correlted est with the numer of uncoted commercil mphioles (P.01) ut lso with the totl numer of commercil mphiole fiers (coted nd uncoted, P.02), with the numer of totl uncoted fiers (sestos nd nonsestos minerl fiers, P.03), nd with the numer of sestos odies found in digestion smples y light microscopy (P.03). No correltion ws found etween the firosis scores nd the concentrtion of coted commercil mphioles, noncommercil mphioles, chrysotile, or nonsestos minerl fiers. Bsed on their firosis score, 7 of 82 (9%) DPF cses fell within the 95% prediction intervl of sestosis sed on sestos ody counts y light microscopy (Figure 1). After excluding from nlysis the 5 sestosis cses contining predominntly noncommercil mphiole fiers (Tle 3), 3 of 86 (3%) DPF cses fell within the 95% prediction intervl of sestosis sed on the totl commercil mphiole fier count (Figure 2). In 42 of 86 DPF cses the commercil mphiole count ws elow the detection limit. These cses were included in Figure 2 t hlf the detection limit. Twenty-five of 83 (30%) DPF cses fell within the 95% prediction intervl of sestosis sed on the totl uncoted fier count (dt not shown). The chrcteristics of the 3 DPF ptients whose commercil mphiole count showed overlp with the 95% prediction intervl of sestosis re shown in Tle 4. COMMENT The current nlysis is follow-up of previous study y Roggli. 10 The former study included 36 ptients with sestosis nd 24 with DPF nd exmined the reltionship etween firosis nd uncoted fiers detected y SEM, totl fiers (coted nd uncoted) y SEM, nd sestos ody counts y light microscopy. In contrst, the current nlysis included 163 ptients with sestosis nd 86 with DPF nd exmined the reltionship etween firosis nd 8 different prmeters: totl (coted plus uncoted) commercil mphiole fiers, uncoted commercil mphiole fiers, coted commercil mphiole fiers, totl uncoted fiers, sestos odies (light microscopy), noncommercil mphiole fiers, chrysotile fiers, nd nonsestos minerl fiers. Both studies showed high lung fier urdens in ptients with histologic sestosis s defined y the 1982 CAP NIOSH study, thus confirming the utility of these histologic criteri. 1 In ddition, oth studies showed strong nd sttisticlly significnt correltion etween the severity of firosis s ssessed histologiclly using the CAP Arch Pthol L Med Vol 134, Mrch 2010 Asestos Fier Content Schneider et l 459

4 Figure 1. Liner regression nlysis of the reltionship etween firosis score (x) nd sestos ody count y light microscopy (y) (regression eqution log 10 (y) 0.144x 4.05). The upper nd lower lines represent the 95% prediction intervl of the model (ornge, sestosis cses; lck, diffuse pulmonry firosis [DPF] cses). Seven DPF cses fll into the sestosis intervl. At firosis score 3, two cses overlp t 3.01, nd t firosis score 4, two cses overlp t Figure 2. Liner regression nlysis of the reltionship etween firosis score (x) nd totl commercil mphiole fier count (y) (regression eqution log 10 (y) 0.131x 5.06). The upper nd lower lines represent the 95% prediction intervl of the model (ornge, sestosis cses; lck, diffuse pulmonry firosis [DPF] cses). Three DPF cses fll into the sestosis intervl, two t firosis score 3, nd one t 4. The 2 filled squres together represent the 42 DPF cses for which the fier count ws elow the detection limit. Tle 4. Chrcteristics of the 3 Mle Ptients Whose Amphiole Fier Count Fell Into the 95% Rnge of Tht Seen in Asestosis Ptient No. Age, y Dignosis Exposure, Durtion 1 75 Pulmonry firosis, lung crcinom, Sheet metl worker, Smoking History Pleurl Plques Firosis Grde Totl Uncoted Yes sttus post rdition therpy shipyrd, 24 y pck-yers 2 59 Diffuse interstitil firosis Foundry worker, ND ND No ND Diffuse interstitil firosis ND, ND ND ND Arevition: ND, not documented. Firosis grde ccording to Tle 1. Fiers 5 m or greter in length per grm of wet lung tissue. NIOSH criteri nd the lung fier urden s determined y SEM, consistent with oservtions from prior studies Our liner regression nlyses in oth studies showed wide sctter of the dt, consistent with individul vrition in response to given fier lod. In our prior study, the est correltion of histologic firosis ws with uncoted fiers detected y SEM. The present study further exmines this reltionship with respect to fier types. The min fier type in the popultion studied ws commercil mphioles (mosite or crocidolite), nd the est correltion with severity of firosis ws found for uncoted commercil mphiole fiers (P.01). As with our prior study, there ws lso significnt correltion with totl uncoted fiers. Unlike our prior study, there ws significnt correltion etween firosis nd sestos ody counts y light microscopy (P.05 versus P.03). These results re not surprising ecuse most of the uncoted fiers in our sestosis popultion were commercil mphioles, nd commercil mphioles constitute most of sestos ody cores. We found no correltion etween firosis score nd noncommercil mphioles, chrysotile, or nonsestos minerl fiers. These oservtions re similr to those reported y Churg nd Vedl 15 in study of workers with hevy mixed mosite nd chrysotile exposure. In 5 of our sestosis cses, the noncommercil mphiole fier count ws 36 to 230 times (medin, 38) greter thn tht of the commercil mphioles (Tle 3). Hence smll percentge of our cses of sestosis re cused y exposures to noncommercil mphiole fiers. The 460 Arch Pthol L Med Vol 134, Mrch 2010 Asestos Fier Content Schneider et l

5 sources of these noncommercil mphioles vried nd included tremolite contmintion of chrysotile (cses 1 nd 4, Tle 3), tremolite nd ctinolite contmintion of vermiculite (cse 5, Tle 3), environmentl exposure to tremolite nd ctinolite (cse 2, Tle 3), nd exposure to nthophyllite during the mnufcture of cement pipes (cse 3, Tle 3). We excluded these cses from our nlysis of the reltionship etween firosis score nd commercil sestos fier count. As in our prior study, the current nlysis shows tht DPF cses tht do not meet histologic criteri for the dignosis of sestosis hve in the vst mjority fier urdens elow the 95% prediction intervl for sestosis, despite exposure history. Thus, the fier urden nlysis supports the interprettion tht these cses re not sestosis. Although one might rgue tht chrysotile my e the culprit in some of these cses, this is unlikely ecuse on fide cses of sestosis cused y chrysotile hve redily detectle chrysotile (nd tremolite) fiers y electron microscopy nd lso meet histologic criteri for sestosis in finding sestos odies in histologic sections. 16 Similrly, it is lso unlikely tht the firosis ws cused y fiers shorter thn 5 m in length, s fiers in this size rnge hve not een demonstrted to e firogenic. 17 Contrry to our prior study, there ws some overlp etween the DPF group nd the sestosis group in the current nlysis. This is of prticulr interest for the 3 cses with commercil mphiole fier urdens overlpping with the 95% prediction intervl for sestosis. Such rre cses proly re true exmples of occult sestosis s originlly proposed y Churg. 18 Possile explntions for such cses not meeting histologic criteri for sestosis include poor coting efficiency (ie, sestos ody formtion) for some individuls nd smpling error relted to vriility of sestos odies in histologic sections. 19,20 None of the DPF cses in the present study hd noncommercil mphiole fier levels pproching those seen in noncommercil mphiole-relted sestosis (Tles 2 nd 3). In ddition, there were 7 cses with sestos ody counts (s determined y light microscopy) overlpping with the 95% prediction intervl for sestosis. None of these 7 cses hd commercil mphiole fier levels within the 95% prediction intervl for sestosis. Some individuls re prticulrly hevy coters (eg, welders with hevy lung urden of iron oxides) so tht high percentge of their commercil mphiole urden consists of sestos odies. 19 We do not ccept such DPF cses in which only the sestos ody counts (ut not commercil mphiole fier counts) overlp with the sestosis group s true exmples of sestosis. Indeed, flse-positive dignoses of sestosis my result from lortories using light microscopy sestos ody counts lone in the nlysis of cses tht do not otherwise meet histologic criteri for dignosis of sestosis. In summry, most DPF cses studied here did not contin sestos fiers in numers within the rnge typiclly oserved in cses of on fide sestosis. We conclude tht strict histologic criteri such s the Helsinki criteri re useful for the positive identifiction of sestosis mong cses of dvnced pulmonry firosis. A history of sestos exposure lone is not sufficient for dignosis of sestosis in ptients with DPF. 21 If sestos odies cnnot e detected y light microscopy in cses with compelling exposure history, fier nlysis y electron microscopy nd energy-dispersive x-ry nlysis my help void flse-negtive dignoses, nd its use should e considered in these uncommon cses. Tissue sestos nlysis is not necessry in cses with clssic histologic fetures of usul interstitil pneumoni (ie, honeycom chnges, firolstic foci, nd sence of sestos odies). References 1. Crighed JE, Arhm JL, Churg A, et l. The pthology of sestos ssocited diseses of the lungs nd pleurl cvities: dignostic criteri nd proposed grding schem: report of the Pneumoconiosis Committee of the College of Americn Pthologists nd the Ntionl Institute of Occuptionl Sfety nd Helth. Arch Pthol L Med. 1982;106(11): Wrnock ML, Wolery G. Asestos odies or fiers in the dignosis of sestosis. Environ Res. 1987;44(1): Roggli VL, Prtt PC. Numers of sestos odies on iron-stined tissue sections in reltion to sestos ody counts in lung tissue digests. Hum Pthol. 1983; 14(4): Roggli VL, Shrm A. Anlysis of tissue minerl fier content. In: Roggli VL, Oury TD, Sporn TA, eds. Pthology of Asestos-Associted Diseses. 2nd ed. New York, NY: Springer Science nd Business Medi; 2004: Asestos, sestosis, nd cncer: the Helsinki criteri for dignosis nd ttriution. Scnd J Work Environ Helth. 1997;23(4): Trvis WD, King TE, Btemn ED, et l. Americn Thorcic Society/Europen Respirtory Society Interntionl Multidisciplinry Consensus Clssifiction of the Idiopthic Interstitil Pneumonis. Am J Respir Crit Cre Med. 2002;165(2): Sporn TA, Roggli VL. Asestosis. In: Roggli VL, Oury TD, Sporn TA, eds. Pthology of Asestos-Associted Diseses. 2nd ed. New York, NY: Springer Science nd Business Medi; 2004: Roggli VL, Prtt PC, Brody AR. Asestos content of lung tissue in sestosssocited diseses: study of 110 cses. Br J Ind Med. 1986;43(1): Roggli VL. Tissue digestion techniques. In: Roggli VL, Oury TD, Sporn TA, eds. Pthology of Asestos-Associted Diseses. 2nd ed. New York, NY: Springer Science nd Business Medi; 2004: Roggli VL. Scnning electron microscopic nlysis of minerl fier content of lung tissue in the evlution of diffuse pulmonry firosis. Scnning Microsc. 1991;5(1): Wgner JC, Moncrieff CB, Coles R, Griffiths DM, Mundy DE. Correltion etween fire content of the lungs nd disese in nvl dockyrd workers. Br J Ind Med. 1986;43(6): Whitwell F, Scott J, Grimshw M. Reltionship etween occuptions nd sestos fire content of the lungs in ptients with pleurl mesotheliom, lung cncer, nd other diseses. Thorx. 1977;32(4): Wrnock ML, Kuwhr TJ, Wolery G. The reltion of sestos urden to sestosis nd lung cncer. Pthol Annu. 1983;18(2): Ashcroft T, Heppleston AG. The opticl nd electron microscopic determintion of pulmonry sestos fier concentrtion nd its reltion to the humn pthologicl rection. J Clin Pthol. 1973;26(3): Churg A, Vedl S. Fier urden nd ptterns of sestos-relted disese in workers with hevy mixed mosite nd chrysotile exposure. Am J Respir Crit Cre Med. 1994;150(3); Holden J, Churg A. Asestos odies nd the dignosis of sestosis in chrysotile workers. Environ Res. 1986;39(1): Agency for Toxic Sustnces nd Disese Registry. Report on the expert pnel on helth effects of sestos nd synthetic vitreous fiers: the influence of fier length. Octoer 29 30, 2002; New York, NY. 18. Churg A. Occult sestosis. L Invest. 1982;46:13A. 19. Roggli VL. Asestos odies nd nonsestos ferruginous odies. In: Roggli VL, Oury TD, Sporn TA, eds. Pthology of Asestos-Associted Diseses. 2nd ed. New York, NY: Springer Science nd Business Medi; 2004: Morgn A, Holmes A. Distriution nd chrcteristics of mphiole sestos fires, mesured with the light microscope, in the left lung of n insultion worker. Br J Ind Med. 1983;40(1): Jones RN. The dignosis of sestosis. Am Rev Respir Dis. 1991;144(3, pt 1): Srero SH, Roggli VL. Asestos-relted disese ssocited with exposure to sestiform tremolite. Am J Ind Med. 1994;26(6): Arch Pthol L Med Vol 134, Mrch 2010 Asestos Fier Content Schneider et l 461