Document LK9q5RgzDYLDvOr7j2V0w8NLd

Pulmonary Manifestations of Vinyl and Polyvinyl Chloride (Interstitial Lung Disease)* Newer Aspects . M. Curdasco, XU)., I X X .P.. S. L. Done ter. M.D., J. Kcrka,,. Ph.}).; 11. S. \ 'an Ordstrand. M l).. I'X'.C.P.. V. Lucas. M.D.; T. Chen, Ph.D and}. A. Colish. M.D.. I'.C.C.P. Newer varieties of occupational lung diseases primarily due to the vast increase in industrial technology has c been reported recently. Preeminent among such newer agents are vinyl chloride (VC) and polyvinyl chloride. Very few cases have been reported, in Kurope only, with descrip* the histopathologic changes. To our know ledge, no path* ologic studies of VC exposure have been described in the American literature. The biopsy abnormalities in our patients disclosed desquamation of alveolar macrophages into the ah cotar lumina and minor interstitial and alveolar inflammatory changes. Pulmonary function ab normalities included restrictive insufficiency. Preventive therapy consists of the avoidance of further exposures, frequent industrial hygiene monitoring, and total avoid ance of tobacco smoke, as well as associated atmospheric pollutants. Thus far. none of ihexe patients has exhibi ted evidence of pulmonary neoplasm. AH three patients survived their occupational injuries, and (wo are still disabled to varying degrees. L'rine and blood levels of phthalic acid derivatives were elevated in two patients, the exact significance of which is not fully known. !l probably represents a toxicologic response, but must be further pursued before conclusions can be reached. TV" ewer varieties of nccupntinn.il lung <1 isenses- have been reported recently, primarih dm to pro found advances in industrial teclmologv Preeminent among such newer agents are vinyl chloride (VC) For editorial comment sec page 826 and poly vinyl chloride i l'Y< ! t. substances used r\. tensively in the plastics indiMr.. \|utc than 1 S bil lion lbs were produced ill 1972 vs itli appmscnati |v 25 percent produced in the Minted States lii iumi 36.000 and ">0.000 workers u en exposed at that time to VC or PYO in mi's, either du: mg the p d \ ; n< ! i/alion process or dining the processing o! finished products.` The number til people exposed. owing either to alteration of (lie finished product or dc- *Kmm the Cli-seLim! ('turn J'lint.daf: >n and f'I-*s > I.i>;I Male Tniv ersity (lies eland, a ml Nortin a -11 ri i 1'inu rate ' V liool of Me<lu llll'. It.lM'lllU Oil 1.1 Mj miser ijlt let ets cd \ mMisI g I. r. \ i..< r i< i . pi- .1 |,i n:.1 r\ 2'l Jh / 0)1/1 Ji i)U( \ti. f if t 'll!.: Ln.il 14 Mi'i C < i.ia . t.; i i . stmetion of these products, or .simple to ]j\ jug near a plant where any of those diverse processes mu\ take place, is unknown. However, evidence lias been piesented that such exposures may be harmful. Accord ing to a recent Knvironmeiilul Protection Agency report, approximated 00 million kg of PVC! are discharged uimuaJly into the atmosphere.' The emergence in 1074 of VC as a new occupa tional carcinogen, producing augiiisarcoma of the liver, focused atteiilnm on other tnvindngic manifestations of this group of chlorinated hv dr<u arlions. Pulmonary effects were first described in 197(1, but few cases have been reported characterizing the histopathologic changes of the human respiratory tract, all published from abroad. Three patiYnls with extensive exposure to the fumes of either V( i monomer or P\'C are herein reported. Lung biopsy results and the implications of their exposures are discussed. In addition, ultra* microscopic findings are included, and new b:o* chi tmeal analyses ale i> ported in two patients, A sumiiiarv on this subject of PVCbinducrd disease was presented hv liie authors at a s\ mposium in the Soviet L'nion in October 197S.' Mvri an vt.s v.M) Mt'/nnms Our c\pci ii'lHinsulsrs tin duirii.ois ahd IIU 1.1 :Jt ment of tlircr p.itunis \s il!i a }i.ii!i'>lo"a di.iL'uo-is uf ini'"'- t'jl fihro* sis and \s urk related rs))-isii i . (., 11) n : \ ft o: !'\(. Jits of Mill.I, \11 l(iM . Ji.iln-nls li.il] a Inn;: Inop-a. 11:i !r,Ill-In.111- 1 lil.ll Jm! dll'' I >\ up.'ll )ln llri.l t'lllln. in.ns tlimlinii studies VMir il.ili.- !> I1.. Ns stems It.-sc .1 i l 11 | .jla U ,il 'll \ III. I In a! .11 a i II k luilstl tola! 1 11. l! 1 ap.lC- il\ til.mm! s It..! raJJa. it>. fl"'S r*U\ JTTvf fT:f!i.s: >1. capacity with . .ulioii ii i< u.< >> i Jcf Arterial t il< iorl u.is tii Jl riiun.it if ms Wi u ]k ilinin. i| i.y 4VI .islnitni ntatiuli l..d>Mf.' : y mclllild. ami hist i'it ill t < mi studies si i ii tic .him i! with the nitmgcn is as!c nit method Iti.iiline m r.-ciiitit' tests included compliti: Mead counts ifiHC uriii.ih sis. scruln"'. SAIV-I2 i!.viii'lr> profile, |.n:> alld 'pnllini studies far routa.- I..1I N ff ] !\1\ MuC.lfs and c-idhires of sjiiitmu far fmO and \| seal ..r. leriun. were also ji. if.inni d f'.uli p.ili, nt also liat! a -pefcm isiolo.jie I S Ii;i .11 . ., 111 .. 11 ill I^>. Ii-I i '.M v, !I i! . I! Is ! i pal !<-1.1 am! e d. fait I I| mlei l!n i't <! . n - `a >:. 23 COF.DASCO ET AL CST n i DC:VE[R 1920 URL 07815 URL G7816 Case 1 > ""-year-old w inn.in h.ul an I`'in. mill history of tongl, uic ^guc and a six-month history of progressive rkspni .1 and digital cyanosis. At the piesont time tin1 cough " drv. occurring in paroxysms. it in.iy In- initiated by breathing (Wply nr changing jmsitions. Medical history, family history. travel history. ant! review of systems were tmncimtrihiitory. SI it* li.nl never smoked or had any pulmonary symptoms until the onset of her present illness. For fin- lust 2ft years tin- patient lias liern employed us a Ficure 1A. X-ray of chest. Diffuse nodular pneumonitis. --" Figure IB and JC. Diffuse fibrosing pneuninnitis with inter stitial thickening and det(|uamatinn of crib into alveolar lumen. 1111 .11 " ' appe1 t lie pi or v.s tliv n|\ rs tut I mi: ,11 i'l sealing tf < | ji.isl n w I .ip i ' Iih 11111 g It 011 .1 hot v 'll 01 hot I .T I ti.. tsl 11 ;,)M, v\ 111 k 1 1 i vs 11) 1 .idiiesne l.iiwl sl-iinpinj dining 1 i- past yi.e Sill his nevri < vpei inn i'll cough or sbiiitnrss ot breath Jh rel.itmii In her work esp.isme. llimrviT, she i| ,es st.iir th.il lu r l.itigm- ts more piiiliimii! as the week goes on and tli.J < '.nli Siiml.iy night is her licsl time. 'I 1 *< faligMi has lessened mm that site limits her work to two-day periods. Physical e\.mini.il urn ii Mills wi n- noiinal except lor (he longs and hands. There were fine inspiratory craekdcrx heard diffusely met (In linn: lielils hot .......... pr oiinm 'lit !v at tin bases Their wen no vvliei/c.s. All (miters showed clubbing, tins .ippar- fiitlv had nciiirred met the lost sl\ liionllis. I lei toes were normal. I..dim.lion \ allies, which "ere iKinual. in- hided CBC. h\er ami renal futulmu tests, urmalysis and hkO. A liypcisinsitivjlv siii-en lor various limit: "as negative. The sedi mentation rate, latex fixation, rapid plasma r-agin ( Ill'll 1, iintiiiiieli ar antibody 1 \\.\l, and <Th| wen- ah noim.i]. C1re11l.il mil immune complexes hy < Mi phindi nc uss.iv were negative. The Ivmplux v le traiislorm.ition test ag.inisl |`\ C "as also negative. 'I he chest \-r.iy film revijletl dill use rctu ulnnndlil.ir ill.mues. Doppler ultrasound ev.im i nation of tin- fi 11 iters, demonsl rated decreased blood flow, more pm- nuiiiifal alter enhl exposure. I'uliimiiiiiy film tioii study dis clos'd .1 restriitivr alilionnalitv (the vital cap-nils ".is Bl percent oi pirdnted in.iiu.iM, with a dilliismi! i .ipaiily (DI.iiii of 11.2. ()li>er new lests inilmled a blood level for the measurement ol plithalu arid derivatives, namely phthulii anhydride. J decomposition product nf PVC, which measured S2 S tig/inl, which is considerably elevated. The urine test for thermoplastic products revealed a remarkable elevation ol two components--the phlhahe anhydride deriva tive diethv Ihevvl phllmlntc known as Infill', mil another component that has been unidentified to dale ami j> probably u laity acid ester. These tests were jicrlonned at the Cleve land State l llivi-rsity Biochemical laboratories. It is tllO opoiii in of the biochemists that these lev els are significant and have been demonstrated in animal studies using P\'C tubing when the F factors are at a range assi^-iatod " ith the release of thermoplastic resins and deriv ntiv-v This aspect of the study is still being assessed. and a luturv report i- planned for publication. It vv.is thought that interstitial fibrosis act minted for the patient's signs, symptoms, and lalnimtorv abnoinuilitii's. It was fiiithei thought that she also showed signs of J'VC exposure tnvii its vv itll digital angiitis. \\ V postulated tli.it the interstitial fibrosis may have been induct'd by her P\ C exposure. Accordingly, she underwent an open lung biopsy of the right lower lobe for pathologic confirmation x-ra> film of the eliest ihselosed a diflnse nodular pneumonitis without Joiah/erl disease ( l'ig 1 \ 1. 'I'here were no pleural or hilar abnormalities. I.ight microscopy (fig IB and 1C) ilunonsti.iti d dilluse filuosmg pileimiomtis with prominent tcrmnul lirnm luolar cell hyperplasia of the alveolar lining or ilesipia- matiom limiiniiolluoreset'iui' was negative for eonipk'rncnt and immmiogl. ibiilios. barge niimlvrrs of alveolar macro phages containing ph.igoi y t i/ed material of undetermined l oil 1 posit imi was seen on electron niiimSi o]'\ (l'ig 2). All inllmi s ol lung tissue were negative. The special blood and mine studies for (het niopl.ist ic resins w ere posit tv e and w ill In- lot tlier pm sued. I hr jv.it l< lit vv ,ts disth.il ged invu mg H) nig o| pi ednisi me per vlav . Cr `lu i;i eu/ This patient showed in msjve, il; sign- and symjvtoins of lilirn.smg uiteisliti.il jmeumomti' v>|iith was CHEST, 78. 6, DECEV.SER, 193D PULMONARY MANIFESTATIONS OF VINYL AND POLYVINYL CHLORIDE 629 Figure 2. Alveolar macrophages with phagocytized ma terial ^electron micrograph). confirmed by biopsy specimen. There 'vj> .ipp.irenib riti evidence of a hypersensitivity reaction either l>y history (ty-pr II). laboratory' (type IV). or immunupathology (type' II or 111), according to (he criteria proposed by McCornlri as a modification of the Gel] and Coombs classifi cation. Digital angiitis. its demonstrated here. cun be a manifestation of l'VC toxicity. Case 2 A fl-year-nhl man complained of "not foehns; well." For the past Ti years he had experienced \ague fechngs of not being in good health, with weakness, faticue, diffuse arthalgtas. ansi myalgias. In the hist eight months he had noticed an accentuation of his symptoms as we)! as dv spne.i on exertion, v'liec/ing .mil a productive morning cough, A diagnosis of asthmatic biombith vv.i made at tliat time, and he w.ls given multiple drug' without linpnwi-ment. Three months before referral, lie was hospitalized at another institution for further evaluation. A bromhoscopy was nega tive. and transbronehial long biopsy uf the right lower lolse was reported to show pigmented mac roph.iges in the air spaces. The chest x-ray film showed men .i-ed interstitial markings Sputum examination showed mode 'ate WRCN and alveolar macrophugi s I .aln >i utnix ti st results, winch were normal, included latex fixation, A\A, \ DHL. KCC*, and sputum cytology. Serum mimnimcleetrophorcsix revealed dp. creased lgM. slightly decreased IgA. and normal IgG. Tulmon.irv funetmu shnbes showed a decreased 1'aO with small airway- di'r.i'0. An rvrro'C tulet.inu' li'st wa perforuu d and itldiuled tliat the patier:t was lape-le of m -iier.ilc ewnisr. tic u.o given broiH )'.! l.ifo;- jr? .ir,!-'- -. w,!b in' r<'. 830 CGRDASCO ET AL sjinhw , ami later, eortiv osti-r,,i(h z f.<r .sn-sjhft ? cnnriectivc t issue disease : veil li a f ,iv orable iespouse. Me returned to work after two weeks and again noticed myalgias rind arthralgias, easy fatigability, exhaustion toward the end of the day, and 'tiffness in his joints. Mu was referred to this institution for further ex aluation. For the past 1-5 years he hud been employed in the dental mold industry and had extensive daily use of VC spray paint. Hex iew of sy stems, family history, medical history, and expo sure history were otherwise negative, lie had smoked one half pack of cigarettes per day for the last five years. The initial ph'sica! examination result' were normal. The lungs were clear. A rheumatology consultation revealed nn cv idel tee of connective tissue diseaw. I .a I xiratury and roelitCenographic examinations wire positive for osteoarthritis. Normal nr negative laboratory tests included all hCXl. scrum T,, T,, anti-thyroid binding globulin, VDRL. sedimentation rate, l.iley fixation, J,K cel) prep. A\A, urinalysis. CBC, SMA-18. and seruin protein electrophoresis. The chest x-ray film showed diffuse, small, interstitial, and nodular densities siattirecl throughout both lung'. The patient returned to work. Mis symptoms were stable over the next two months; hnvvrver, (wo days before his admission, he complained of a ''flu-like" syndrome. with un ifu rra'i- in his generalized aching, a slight, dry cough, "an increase in shortness of breath, and chest tightness. On examination he was afebrile, wit It few hihasdar erepitant rales and a palpable lymph node in the right suprael.iv ieulaf fo'sa An iimminoglohuhn elec ti ophoresis now showed in creased IcA ( T><). normid, l5fi *12 ), low normal IgM <51; normal, MS ^ 105), and decreased IgG (050. normal, 1,'JSO 2: 255 I. The remainder of Jaliorafury and physical examina- I'l'i 'U 5 Thitkinid .ibenlar septum with accumulation nf nit.i nui Ie.tr eel!- al'-eo).,r macrophages .niih'acotic pig- TT:i * it CHEST. 78 6, DECEV.BEfi. 1980 URL 07817 {ion results cn* unchanged- The chest x-ray film un- . i f :nill m as uiti r pn ti il by tlir 1J.( )/1 C classification j* l/1 'n biop'y. tin* lymph node showed lustioey ton consistent Ath chronic inllanim.ttion. lie underwent a trephine June biopsy, which was reported to show large numbers of aKi olar macrophages in the alveolar air spaces, thickening of the peribronchiolar connective tissue, and al veolar septa with accumulation of mononuclear cell. and anthracitic pigmentation, hypertrophic hronchiolar epithe lium. and macrophages containing large amounts of hemo siderin and j few untilracoLii jiigiiiiiits ( I* g -3 ). The patient was dist barged nt-iiviug curt lorstcruicls, with gradual clearing of his symptoms over the next 2'j years. F<>|lnw-iip laixualory exanunalion results have remained un changed. The chest x-ray film has rciiiained abnormal. Comment: The bmp-y speunuu showed changes con sistent with interstitial fibrosis; no immunologic testing was performed on the tissue. This pjticnt differs from patient 1 in that his exposure was to the \'C. monomer as opposed tn PVC fumes, Cask 3 This 55-year-old man was exposed to PV'C dust during a jr~ - - " .-* - r:~ -> .if ' t . - -J*. *7-.CS.sWl i' ..i, V'f=*--. -j " . -. t'-- Y r v---- ; -V~* --- JVciu: 4A. Chest x-rjy film abnormality; interstitial infil trates. l i'. i I " e |*i;s >,* j5 fa -\Vt V PJa /???& .Jgr 1`ic.vnc 4B 1 )esi|oam.ition of cells into alveolar lumen reactor eli aning ujxTation. lie was a nonsmnker. His initial esposuie in nirred over a five- to six-week period, resulting in the development of continuous and progressive dyspnea of approximately ten days' duration. He had severe dyspnea in the 24-hour period InTore admission. Air samples of PVC in the immediate operational area varied between 2(X) and 315 parts per million. Examination of the chest showed hihasilar course, inspiratory, crepitant r.des Bemuse he initially failed to respond to oral aminophy'lline therapy piescrilied by his local physician, steroids and Ingli-flow oxygen with a Veiitnri-ly p* mask were added, with considerable suliNcipK-iit iinpms niieot user the next 45 tu 72 hours. There was a gradual reduction of the steroid dose over the next txvo-werk petiod a> the pahent slimvril progressive iniprnvi nieiit. Omcomituntlv. there was complete resolution of the mcnlgcnugruphic lesimis. The pulmonary function tests m tliis perM m disc loved a moderate reduction of \ ital capacity anti in the mid-expiratory How rates and moderate impair ment of diffusion capacity to 12 8. The arterial PaO, mea sured (it) nun llg at ri>nni air. The remainder of the routine laboratory studies, which included an SMA-12 chemistTy profile, urinalysis, serology, and tlllC. were normal, except for imniiua! leukiK > tosis nl 12,200 cells. Figure 4b shows his chest x-ray film at the time of (lie six-week exposure. The histopathologic changes were compatible with a desquama tive interstitial pneumonitis. T1c section of his lung biopsy disclosing tin s* findings is shewn in Figure 4a. Discussion Vinyl chloride (CH.- = CHC1} is a monomer used as a chemical intermediate in the polymerization of PVC resin in the prodviction of copolymers such as Saran, and as a solvent.5 VC monomer under normal temperature ami pressure is a gas (BP 13.5 C). It readily polymerizes under pressure at a temperature of -10 |o 70 C to form PVC. a white, solid material. Although the pnlvmerization process xvas discovered in tlie ISOOx. 1JVC production did not 1>cgin in the LDited .States until 192.S.C The list of materials made from PVC is extensive ami includes foils, films, tapes. tubing. fiber, cables, artificial leather, foam rubber, paint, varnish, toys, and automobile up holster. coverings. Tin- acute, toxic effects of \'C gas (anesthesia and narcotic-effect) were* quickly discovered and were thought to represent the onlv toxic effect of exposure until 1949. when Tribukh et al`; in Russia reported a hepatitis-like effect following long-tern) exposure. Other toxic manifestations were reported during the 196<lx ('fable 1), and in 1974, tike association be tween VC exposure and angiosarcoma of the liver was made, further toxic manifestations "ere discov ered tluring epidemiologic sludies that were per formed both on production workers and on popula tions living near the plants. Tin' clinical spectrum of FVO-indneed toxic organ damage is broad (Table 11. The most widely reported manifestation is a scleroderma-like syndrome, and tlu- most widely dis cussed is the angiosarcoma of the liver. Table 2 lists C-'LST. 75 . DECEV.9ER. 1989 PULMONARY MAK1FE.STATIOKS OF VINYL AND POLYVINYL CHLORIDE 831 t8 L 0 a u o CD TfiMf 1 -- To.xie KfTert* ttf I C. ami I't (' f.vftomre It? Organ Orpin T<>\ir liff-ii . IJ< f< i< :: - Liver H-paliti- :r li'ViiUii in/vinr-i nr almiiiiii.il liv<i scan Hepai i<- litirniis Antio-ati uiiia :u,:<2 :tn :ui.:n Skin Oi-rm:U il i- i Ti'-cinl i|.' - I. T"' f1 ! m. t 2 2`` Vos.-nlar Dicif.'il aneiiti' ri-niiil'I. Haynan-i'-i Hemal nl< ifrii Tiirmiiliiic \ i.ipi iiia Skeletal Am kiiUiiIv si- x mi 2-1.20 Pulmormrv Aeiita nl >-1 m"' > in Clironi'' airll.i" >1 i-i ru< i u>n Inicr.-ii:al lilir-n-i* 1 2 0,7 21 22.:t2 other manifestations of PYC toxicity. Other than the acute narcosis, the diseases on this list were discos ered by epidemiologic studies and were thought to represent statistically significant association. The teratogenctie effect applies to communities sur rounding PYC production plants. The effects of YC am! PYC exposure on the pul monary system include both acute and chronic air flow obstruction. "Meat wrapper's asthma" is a syn drome of acute bronehospasm tine to the inhalation of PYC fumes from melted plastic wrap It closely resembles an acute h\ pcrseiisith ity response that can be seen with other industrial exposures. but no documented immunologic complexes have been re ported to date,7 with one exception: a report from abroad.* Deereast*d flow rates are also seen with chronic exposure. One studs found a decreased FEVj/FYC ratio in 30 percent and 50 percent of nonsmohers with one to 20 \ears and more than 20 years of exposure, respectively." Another study found decreased How rates in 50 percent of PYC production workers who were older than 30 years.*0 Others have disputed such claims.11 \Vc base re cently encountered three patients with PYC-induced asthma. This is the subject of a separate report. Table 2--\onorfan System Toxic WunifcutatinnM of VC and PVC Kxposure I ,iT< i*l Acute naTcn-is Incre.'Lsrcl rnnrralify Incrcjisfii caiu-iT rail's Chrottm.su!'>:0 aliiinrin.-ilii irs Irirrr.-wsrti i,r:is^ri:',riiv and fi i .' ..r,ii'\ lt.-f.-n in - 1 <.:i t in. I a, l.`i. In.d.' .S.an.aS. ci a*. .<7. m f32 CORDASCD ET AL Tin risk nl pnlnHitiars ni iiphiMiis nia\' ahu !>, highi-r in YC and l`\C prinlm. tinn workers. Animal data aiv liighh i\< ,but the slandai di/ed moitality ratios (SMKs) var\ from 112,In 156,17 100.'' tn IfiS.'0 and other studies could find no intreair in the expected amount nf cancer20 -- Another strnh supports a carcinogenic ellect be- cauxe ot differences in expected cell types (with no increase in the total number of lung canerrs }.-:i In addition, the efleet o! concomitant cigarette smoking is unknown hot probahh additiv. Other industrial cxpoMiies eg. asbestos. chromimii. and chloro- methv I etlvr imlu ate a probable synergism in r.tr- cinogenie efleets. The cell types of lung neoplasms reported hv Waxweilrr are shown in Table 3. Intel M iti.if fibrosing pneumonitis due to PYC or YC exposure lias been irporled onK ravels primal ih from the foieign literature, although nodu lar infiltrates on chest \-rav film haw been described in 3/37 svorkers in one report.*'7 Of 9S5 workers in another study, 13.3 percent showed a similar ahnor- malits (l/d or 1/1, I LO/UO classification ).10 Inter stitial changes have also been delineated in experi mental animals.-* \Yc report three further eases of histologically prosed interstitial fibrosing pneumonitis in patients exposed to either VC or PVC fumes. Signs, symp toms. and laboratory abnormalities do not differ significantly in patients with interstitial disease asso ciated with VC or PVC exposure from those with idiopathic interstiti.il fibrosis. Usual symptoms in clude the insidious onset of dyspnea, exertional weakness, and dry cough. Physical examination re veals fine bibasilar inspirators- crackles. Other signs of PYC toxicity may be seen as well. The chest x-ray Tnltli' 3--I.ittig Cancer Case* HistnluKicatly Canfirmed .Imong Cohort Worker* Cxftnsed in \ ittyl ('hlnritlr! Pntyi'inyt Chloride"11' ( No Hi-m|. >cif 1 linen' >- i- A trrii D-alli, 1Ksi'ii'iirf, L;if "Tn Y, \r \r \r i l.arji- It iiik1i(T< n inini-d 2 l.nrtii- -i'll illn MTiTi-iiI i;U nil 40 11 j:$ fa 18 "A l.aip- i i ll uinltfTi n nr ian-.l A Larin .-i'll iiinliiTi n ininn d 3 l.ariji- ..-!! int< 1 ilTiTi-fjt i:ti fit ">2 Id r, i 22 Hi K 22 17 17 i. A!<-mn ar' iimiiia -t.r> 10 10 7 Adi nn.-.in in.ima >7 12 12 # V<l> in>.-,-in inujua a Ml -Ml Ill-Ill >111.1 " . | i. >- - H !> . Mill | ml It'll 1 72 la 12 22 CHEST. 7S 6. DLCLMCEv !;0 URL 0^819 URL 07820 !m `Vi^ws (lifTnret it u' 1 .' ir infilt i .,h s. pnh o- n ^function testmc dm.- des a r< strictne pat tern ami depression in r he I '>1 t \ wiih \ .triable lex el s of PaOj. TairilJ hiopsv spm - mi -i discloses iulcrsl it ial infiltration with rnonminrh :r <ells. fibrosis. alveolar hvporplasia. an'l drsqu.e i! m into I In* alveolar lumin.L Diagnosis is best e> nfirim'd by lung biopsy. At present it is highly p esumptixo. I>ni strnnglv indicated, that (lien- is e o- 'i-iatimi Ih'Uviv'i the exposures ami tin* develop ant of ii itei shtidl fibiosinj pneumonitis. No c.nn -ciiirt n latinnship can catecoricallv ho proved v. th ecitaintv in such a small series. Hiihcut. lln Mlient with a histnrv <f exposure in the polvmet'i/.dt'nn process coupled with the clinical studies o| min r authors > I .ills Melmti. at id S/.emle ) almost < rr! aii !\ stil isl anl iates tin diag nosis. at least in tin* one pat at it. The mechanism of tin- response remains specula tive. although a (|\ sfuiKtim m the innnuiic s\ stem is probably implicated Of -JI 1 workers in a VC jxK nirri/ation plant. 2s wen- :. mud to has < has nan Is phenomenon. and J!) of (h- 2s wore found to base circulatin'.: immune i'i'ii]uv> * Circulating ervoirmnunoglolmlitis are found u 11 percent of patients with usual interstiti.il fibo-os and pla\ an dialogic role.-y In addition, marhin* *( almormalities of the immune sxstem ( Ian \ f:\atiou. sedimentation rate 1 are found in approxiv aielv 2o to `>0 percent of patients with fibrosing ao<-oi:tis. " It is tempting but purely hvpothx-Jical In 'peculate on an immuno logic basis for tills respnn-< despite the lotal ab sence of these markers in our patients. The other mpehanis'in is foxicologk. uamelv. dose-rfiert nlationship to exposure. In bis review of iili''p..-hT puhnonarv fibrosis. CrvstaP1 points to several \ lues" in attemptin'.: to answer the question "Wh .t tuggers the disease.'" Some "triggers" (or etinlniV I actors 1 found in pa tients with interstitial fihro-t' max include: ( ] in fection (25 to -JO percent d patients antedate their illness to a vital ihest w: bmne': (2' hcreditarv fact'ijs (familial clustering- ami relative inerc.iM in HI.A-12 ami Hl.A-21)' e 1 3 ` i ell-mediated inmuni' reactions {direct'd .igiinst 1mm eollagi u ' Perhaps toxic exposure' i .. nluath ss 111 hint ll ii plats' in this list as more a--m iat ions of the (\pe we have just presented are hnngl.t to light. The identification nt 'a 'lit Ihcv. 1 phlhalate (DEIIIM in the serum mine of imviu' amount (]fx> fillies llj.it o' 'he control ) in one pa tient is itiU'l'rshng and p;. u>alI\ significant, beCvntlv, similar ilexatinu* > liie substance m bolii semm and uiim wen ><L `ti'd in tin- second ;m- tie'it. TIj<' sn1"! iimv i' ipoMliou produ'' < >f l'Vf ` i In 'linealI\ s m lil.ir ' < V ! , v \ I .u h j > C I * .i' 1 1 anp.Mii' ' dies 111iIh \\ 1 ad jmlr a p. (| ,r ciia--siiit( dunn" hot-wire slitting of neat wr.p plastic, as another plastiei/er [iresent in I'\'C. It max also occur as a decomposition product ilnrin^ the adhesive st.jmp-IabeJmtf process The major inun dient of th<` l.itler pi i icrss is dii v eloliexx 1 pl itlialale Four major thermal decomposition products of dies elohexx I phtllalate are cx clohcxanol. dic\ clo- b'X\l other, phthalic anhvdnde. and cvc-lohrvv] ben zoate. 'I he presi nee of tlx-se compounds alon^ with DEMI', was n .idilx demonstrated in llic scrum nnd ui'iiu- of fxx o patients. In adihtion, urine samples also contained sejnilicant amounts of MEIIP (mnno- etlnllu'wl ])lithal.ite j. phthalic acid, benzoic acid, and O and IMixdm.sy hen/nie acid. These urine c> n 11 j >' > i icnts arc probably metal ml it es of DICIIP and other plasticizers present ill l'V(). (annpleti' ex.diia- tion of the metabolism oi decomposijion products of l'\ < ' in man is preseiifls beiui; jmrsix'd at Cleveland Stale l Iliv < l'sitv. I ri -at 11 ii -rif is primarily prophclaetic, with imme diate removal of fix' affected patients from the of- feiidiire fmiH's beimi of jiaramount importance. ( aiifiensleiunls max be helplul in tin- treatment of tin e.uK sieves ol lliis discasx'. Other immunosup pressive a'^enls h.ivi- not been used, to our knowl edge. Tlx- edicaev of steroids was verified in one of our patients and is In'^hlv probable in our second patient \')m had lom'-lerm exposure to ]'V(! fumes. 'I he use of oilier iiimilniosiippressiv e a'ientv has not been re]>orted In mir knoxx letl'^r*. I'ropbx lactii allv. f 11 ( jtlent indnsh ia! h\''ii'tie monitorim; is of utmost importance lor the earlv deteetiou of abnornnil at- inosplierie levels in the occupational environment, (ilose medical sum illaiiee of suxli persons exposed W i\ [)i < \ iiit I he oi < in iriKr i il sr\< t< adverse ht alt h i Ih vis. rosra.r.sioNX I he awareness nf ncxur hazards of chemical sub stances ini n usin^lx presenl in mir cm ironment is of paramount in ipm tancc to ev crx ci nplovee, as well as t'> the ei 11 11 i cm Ml an I ril X . bee.ilisi- oi lln- obvious o( , up.il i<n i.d and 'public licaltb iiuplii at ) ms. Fxatnp!' s oi siioh newer .ilu iiK have bt'-u reported. Ni-vxi'i lilm In inieal studies of botli lie sellim .Did 11: [in . ijol.ibK i |i eoi i iposi li on pi'oiliii [s n| IjiiihkU plaslii n-suis of tin plillialie aeid Croup, weie abi r >i n ill a , ' 'v i patients The I < it ,il el lin< il si Cl ii fir.i I iee ol these f.ietovs is vet unknown and will be further pi 11 sued. Ibis is mil of the fj | ,[ reports in (Ins comillV fo di ilueate lia liislop.il I lolocii < bailees nl the O 'pna!' * i \ 11 a et 111. tt cm i vt: 11111 si i < b r \ e< ss iv i ex posii r< -s of ! ' , \ < I A I _i - op d In i i p> i Mil i1 pb' i! i' ' in- 11 b the 'll > 'Ml'. I >1 I It lit l 11 in! il a! '' i 1 v .'illa'ii * as CnisT. 7s 6. dt::v-r '-i. PUlMGSASr MASIFESTATIONS OF VINYL AND POLYVINYL CHLORIDE 633 w.--1' as tlu* institution of di.mn-''he .mil propin l.a t itij. /.trial hygiene procedure?, on a more fre<juint basis. This is of paramount import.uicv. since XC. and PVC arc toxic agents. Therefore, it is of utmost significance to institute such close medical surveil lance to prevent serious adverse health effects. lU.mtKScrs 1 Berk FD (mod). Vinyl chloride-associated liver disease. Ann Intern Med 1976. #1:717-31 2 Zenz C. Occupational medicine principle* and pmetkes application. Chicago: Year Rook Medual Publishers; 1975:789 3 Cordasco EM, Dctneter S. Pulmonic manifestations of polyvinyl chloride exposures. Presented nt Symposium, Republic Hospital, Dusamhr, Tajiskislan. I'SSR, October 197ff 4 McCoomhs RP. Disease due tu immunologic reactions m the lungs. N Engl J Med 1U72; 28ft:ilK6-<J4, 1215-52 5 Heath C. Klk H. Creech J. Ch araitcristies of cases of angiosarcoma of the liver among \ inyl chloride workers in the United States. Ann N\ Acad Sci 1U75, 2 if) 2.11*36 6 Kramer CG. Mutchler JK. The eorrvlation of clinic.d and environmental measurements for w inkers exposed to vinyl chloride. Am Ind Ilyg Assoc J 1972; 3.1:19-30 7 Sokol WX, Atdony Y. Beull GN. Meat-wrapper's asthma: a new syndrome? JAMA 1974; 222 639-41 8 Ward AM, Udnoon S, Watkins J. Waller AE, Durke CS. Immunological mechanisms in tlic pathogenesis of vinyl chloride disease. Br Med J 1976. 1:9.36-38 9 Miller A. Teirstein A, Cbuang M. SehkofT S. Wur-haw R. Changes in pulmonary function in workers exposed to vinyl chloride and polyvinyl chloride. Ann NY Acad Sci 1975; 246:42-52 10 Selikoff S, discussant in Barnes AW. Vinyl chloride and the production of PVC, Proc R Sr>c Med 1976, 69 277- 8) 11 Camble J. Liu S, MtMichaol AJ. Waxweiler PI Effect of occupational and nonoccupation.il factors on tin- icspiratory system of vinyl chloride and other workers. J Oct up Med 1976; 16:659-70 12 Cordasco EM, Demefor S, Lira R, Wagner VS'. Occupa tional asthma updated. J Occnp Health Safety I960. 49.42-45 13 Lee CC, Bharidan JC, Winston JNI. et .d. Carcinogenicity of vinyl chloride and xmylulciir chloride. J Toxicol En viron Health 1978; 4.15-30 14 Viola PL. Bigott) A. Oupnto A. Om-ogciik response uf rat skin, lungs, and bones to vinyl chloride. Cancer Res 1971; 31.516-22 Malloni C, Lefrniine C. Oari inngvnicity hinassoys of vinyl chloride: current results. Ann \Y Acad Sci 1975; 246:195-218 Tulvrsbaw JR. Caflcy WR, Moilabty studies of himt> in the manufacture of vinyl 'liloridc and i(s pub mors, J Occup Med 1974. 16.599-18 Waxweiler RJ, Stringer W, Wagoner JK. el a!. Neopl.islic risk arming workers exposer! I i vinyl chloride. Ann NY Acad Sci 1976; 271.40-48 18 Mci-nsnn RH. Peters JM. Johnson M\. l'roporlion.d mortal ity among vinyl chloride workers. Lancet 1974; 2.597- 98 19 Byrcn 15, Engholin (7 Englund A, V estcrhnhn I' M it>' and i am ei nmrl-i bt \ in a g-uup of Vw i-ddi V f\f i-v? 634 COflOASCO ET AL ITY pro:!' i< t mn work, > | ie, iron He.dtli I'erspcc f | Q7f> 17 167-70 20 Dink DW. Carter 13. Coondics EJ. Mortality study of workers in a pnb s my] rhloridr production plant. Lancet 1975. 2:1197-99 21 Falk 11, Waxweiler R. Epidemiological studies of vinyl chloride health effects in the touted States. Frm. R Sot Med 1976, 69.303-06 22 Sarii M. Kulcar Z. Znrica M, Gclic I. Malignant tumors of the h'er and lungs in an area with a PVC industry. Em iron J Ic.dlli I'erspect 1976; 17.189-92 23 Mason TJ C.uii-cr mortality in U.S. counties with plasties anil related industries. Environ Health IVrspeit 1975, 1E79-K4 24 Armnid A. I'nmnucr D-S. Garlic L, Payan H, Obarprn J. 1'nls \ ins 1 chloride pneumoconiosis. Thorax 1978, 33 1925 25 Darke CS ( discussant ' in Barnes AW Vinyl chloride and the prodiution of PVC. Proc R Soc Med 1976; 69:277- 281 26 S'zrrido R. Lapis K, Nemc< A, Pinter A Pneumoconiosis caused bv the inhalation of polyvinyl chloride dust. Med Lav 1970, 61.433-36 27 Lange CE, Juhe S, Sit-in 0, Wllnun C. Further results in pobviml chloride production workers. Ann NY Acad Sci \ 1975,216:38-2! _' 28 Prodan L, Sutiu J, Pislaru V, Ilea E, Paseu L. Experi mental chiunic poisoning xs it 11 vinyl chloride (monochloTethenc). Ann NY Acad Sci 1975, 246:359-63 29 Fulmer JD. Clinical aspects of idiopathic, pulmonary fi brosis. in Crystal R(i t moderator ). Idiopathic pulmonary fihrmis. Ann Intern Med 3976; 85.770-73 30 Turner-Warwick M, llosbm P. Antibodies in some chronic, fibrosing lung disease: I. Yon-orgaii-specific anti bodies. CJm Allergy )97), 1.83-95 31 Crystal MC. lbochenncal ennevpts and overall perspective of idiopathic pulmonary fibrosis, in Crystal RG. Idiopathic pulmonary fibrosis. Ann Intern Med 3970, 85.763-S5 32 Vcltman (i. I^angr C-K. Juhn S, Stein C. Bachner V. Clinis a! manifestations and course of vmvl chloride dis ease. Arm NY Acad Sci 1975, 216-6-17 33 Lab' R, Anderson II. Nicholson WJ. i:t al, prevalence of efiseasi among sins! chloride and pohsim] chloride w orkers. Ann NY Ac ad S< i 1975. 2 t(> 22-1J 34 Cn-i-ch JN. Industrial scn-cning. in Berk PI) (modera tor' Vinvl chloride-associated liver ebscass. Ann Intern Med 1976. 81:720-22 .35 M.iislrlbr f|J. fx lli.u li VVK Mm Me r. R, (.edic'k P. I'n- usna) splcnoiiiegjlk hxer disease- as evidenced by peri- lonost ups and guided h\ er bio])->y among p:>1 > vinyl i hlor- ule production workers. Ami NY Aiad Sci 3975, 246 95-13-1 36 Wagoner ,!K. Infante PE, Sar.n ei R. \*jnv 1 chloride and nmri.ilits h Lancet 1976, ? 191-95 r>7 Infante l'F, Wagoner J, Waxweiler R Carcinecenic. unit igenie and lei.itiigenii risks .e-wii i.ited with vinyl chloride. Mut.it Res 1976; 11:1 11-12 5fi Purchase II 11, Uleli.irdsuii tilt, Andristin 1) Chrornnsnriia! and ilominant lethal elin Is of x my! chloride. I...met 1973; 2: 110-1 1 39 Eunes-Cr.iv into E, Lambert R, 1 .inihu n ], et a! Chromo some alienations in worker' exposed to \in\l chloride Laiicrf 197.5 1. 159 1(1 Inf.mte I F. U-agonei JK McMnliael M. Waxwtdcr RJ, J'jlk II. (I'lKtic risks of s ms t i-1 jL- l-.iiK-.t 19.6. I 7 ! 1-15 CHE.ST. 7- 6. 1S0 iJRL 07821