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I EXHIBIT SP*. 23>3 Asbestos Pleurisy H. B. Eisenstadt, m.d., f.c.c.p. Port Arthur, Texas \ SBESTOSIS IS A DISEASE OF THE RES- ~3^ oiraiory svstem caused bv inhalation of asbestos material. The latter name is applied to a group of minerals occurring naturally in the form of fiexible fibers. Of the more than 30 known substances with such properties, only six have a commer cial value.1 Each asbestos mineral has a different composition determining its phys ical and chemical properties. However, all of them are characterized by incombustibil ity, flexibility, tensile strength and resist ance to heat and chemicals.1 Due to these peculiar properties, asbestos has more than 3.000 different industrial applications.1 This widespread use accounts for the great number of workmen coming in contact with the material. Recently it has been stated that "silicosis is not just one disease but many, all of which we may call with this name because of lack of a better term."* A similar state ment seems to be applicable to asbestosis. Differences of mining and milling proce dures, manufacturing and usage of the end product may easily explain the varieties of the clinical appearances of this pneu moconiosis. The classic form of pulmonary asbestosis is described as a bilateral fibrosis which progresses over a number of years and leads to a shrinkage of lung and pleural spaces. From the clinical point of view there is an initial asymptomatic stage lasting a long time: this is followed bv the gradual appearance of shortness of breath, anorexia, weight less, weakness, dry or pro ductive cough, rhonchi. decreased breath sounds, cyanosis and clubbing of fingers. Finally, respiratory failure appears, fre quent:;.' associated with cor pulmonale and right-sided heart failure. Corresoonding to this clinical appearance, the x-ray dims of the chest are initially negative. However. Fr-t-n the Medical Clinic. gradually fine bilateral reticulation ar.ij stippling may be noted, particularly in th middle and the lower lung fields. This pic ture is followed by a diffuse ground-gi^ haziness and by coarse streaking of prac tically all lung portions except the apic^ In the final stage, pulmonary contraction may be seen with fibrothorax. Diaphra2 matic and pleuropericardial adhesions, aj well as parenchymal densities, are respon sible for blurring and irregularity of hean margins and diaphragm characterizing the terminal state. These various x-ray change so well described by Pendergrass3 have been correlated by Lynch4 and others with the pathologic findings. During the first stage, only asbestosis bodies are observed in the otherwise normal appearing tissue section. These club- or spear-shaped bodies renresenting asbestos fibers covered with protein aceous material must be present to make the pathologic diagnosis of the disease. Later, various degrees of pulmcnarv Lnflammation follow, terminating in com plete disappearance of lung structures with formation of hyaline and fibrous masse:. Sometimes, however, asbestosis does not how these typical features. For instance, an interesting case study has been presented by Castleman.5 where asbestosis involved rr.ainiv the upper lobe of the left lur.j This author assumed that an associated burned-out oneumonin was responsible ir: -uch an unusual localization. However, he was unable to establish the exact mechan ism producing the lesion ev en after necrccsy. A completely different form cf asbestos:? presenting itself mainiy as pleural disease has rarely been mentioned in the literature. To be sure, involvement cf the pieura hu: been described in a number of cases. How ever. this has been considered to be a iat: and insignificant complication associated with extensive pulmcnarv disease. The following or. ptosis appearing Pleurisy "'hich dm classic picture. In September. 1961. 3?besos insulator^ V acute pan in lhc ! aggravated by cou. isart from simp.e co: to* any respiratory ' U* patient did not so elev2:ion ' ` 'Jd be detected in r. Vis a dullness to pen V brea'b sounds in ths Vvture demonstrated a Icmpatible with a d,aT tang* and heart appt -pc^nal on the chest pi icos included a siight tim rate and a norm; ah,is. Skin tests for .-.sections were negam *-d electrophoresis we ctjII amount of muc .-rated: it did not con: robercle bacilli or othe ams. No paracentesis ' tie excellent general .Viter two weeks of be -Cctelv and his chest > Hi-wever. six months : crnilar episode in his r: r-e. the onset of the c -uh soreness, nausea. S?-. -&f .- - ; vL:.;' :-V * Benign : rulation and :uiarly in the ids. This pic. ground-glass ;>ng of pracv, the apices. c contraction \. Diaphragadhesions, as . are respon.rity of heart icterizing the .-ray changes >s3 have been ers u'ith the :e first stage, erved in the issue section. todies reprewith proteinent to make * * disease. /iary in- ng in comuctures with rous masses, is does not or instance, en presented 'is involved left lung. . associated oonslbie for however, he : ct mechan:ter necrc-p- d asbestosis iral disease literature, pleura has ases. Hcw be a iate associated i ) > ' ) ( ;1 ; t ii \ ] 1 . i ; V.iium* 46. No. I ASBESTOS PLEURISY 79 The following case illustrates a form of -vsbestosis appearing primarily as idiopathic pleurisy which differs greatly from the classic picture. In September, 1961. a 34-year-o'id white man, 3n asbestos insulator, was seen suffering from 3n acute pain in the left hemichorax. The pain was aggravated by coughing and deep breathing. .Apart from simple colds, he had never suffered from any respiratory disorder before this time. The patient did not look seriously ill. He had a lemoerature elevation of 9$.ST. No abnormality couid be detected in his nose and throat. There was a dullness to percussion and a suppression of breath sounds in the left lower chest. An x-ray picture demonstrated a density over the left base compatible with a diagnosis of pleural effusion. Lungs and heart appeared otherwise perfectly normal on the chest plate. Laboratory examina tions included a slightly accelerated sedimenta tion rate and a normal blood count and urin alysis. Skin tests for tuberculosis and fungus infections were negative. Studies for L.E. cells and electrophoresis were non-revealing. Only a small amount of mucoid material was expec torated: it did not contain pus cells, eosinophiles. tubercle bacilli or other pathogenic micro-organ isms. No paracentesis was performed because of the excellent general condition of the patient. After two weeks of bedrest, he recovered com pletely and his chest x-ray film looked normal. However, six months later, he suffered from a similar episode in his right side (Fig. 1). At this time, the onset of the disease was more insidious with soreness, nausea, anorexia, 'weakness and weight loss. There was a splinting of the right hemithorax; a loud friction sound couid he heard on respiration. Thoracentesis was performed and 550 ml. of brown-colored fluid were aspirated. The fluid contained red cells, lymphocytes and reticulocytes in the sediment: no tumor cells and no pathogenic organisms couid be detected. A culture of the fluid showed no growth. The mucoid sputum contained staphylococci and streptococci, but no tubercle bacilli. The sedi mentation rate was 83 mm. per hour (Westergreen). A latex agglutination test was positive in a 1:80 dilution. The blood count revealed a moderate eosinophilia. but was otherwise normal. The patient was placed on a medical treatment with antituberculosis drugs and bed rest. How ever, he showed little progress after a period of one month when the pleural tap had to be re peated. It yielded 450 ml. of fluid similar to that previously encountered. Finally, after an additional month of waiting, thoracotomy was carried out. Extensive pleural adhesions were found obliterating part of the pleural cavity. There was considerable thickening of the visceral pleura (Fig. 2). Decortication was performed Figure lBenign pleural asbestosis rieht;. Figure 2: Dense connective tissue with infiltrates of lymphocytes and eosinophiles. removing ait the abnormal tissue, (r. addition, a specimen of the adjacent iung was obtained tor microscopic examination. The latter revealed thickening of the aiveoiar walls with rr.acrcohaees and asbestosis bodies Tig. 5 . The pa tient recovered compiereiy after the operation: he has remained in good health ever since this time. T.-^erp .`I t i So H. 3. EI3E.VSTADT OcishfitsCeshfojff Volume -i<\ No. 1 lul'- E'^-t Comment Asbestosis presenting itself clinically and roentgenoiogicaliy primarily as a pleural disease has apparently not been described in the literature. Such a form of asbestos disease has not been mentioned in the re cent textbooks on this subject.*" However, it is not difficult to understand why the condition could have been overlooked. Be fore the advent of modem thoracic sur gery, any idiopathic pleurisy was consid ered to be caused bv tuberculosis until proved otherwise and* treated routinely with an antituberculosis regimen. Benign asbestos pleurisy resembles tuberculosis closely in its appearance; it is apparently a self-limited disease of several weeks' or months' duration and therefore, may give the erroneous impression of being benefited by antituberculosis therapy. Apart from the history of exposure, nothing distin guishes this disease from pleurisy of any other etiology. Surgical exploration with pleural and pulmonary biopsy is needed to verify the diagnosis. Marked pleural thick ening, hyaline and fibrous plaques, non specific granulomas and extensive adhesions may alert the experienced investigator to consider the. disease. However, the final diagnosis rests in the demonstration of asbestesis bodies in the lung parenchyma. Unfortunately, these needle- or club-like formations are hardiv ever found in the pleural specimen. Our own patient would probably have completely recovered with prolongation of this conservative management. However, the exact etiology of his pleurisy would never have come to light without thoraco tomy. Our suspicion of primary pleural asbesrosis in this case was partly aroused by the history of prolonged exposure to this material. In addition. \e were alerted bv our previous experiences with two case? of malignant pleural asbestosis. i.e.. with ma lignant pleural mesothelioma associated with and probably caused by asbestos dis ease. One of these patients suffered from unilateral pleuritic pains for a period of 12 years prior to the development of the ma lignant growth. These pains must have been caused by a benign process preceding the malignancy. Another case of asbestosis and malignant mesothelioma5'* previously described by the author had benign bi lateral pleural effusions ten years before his terminal illness. His chest roentgenogram revealed bilateral streak-like basal calcifica tions of the pleura considered characteristic of asbestos disease. At necropsy, both pa tients had shown pulmonarv and pleural changes typical of benign pleural asbestosis (Figs. 2 and 3) in those portions of the I i { tti, j j d!& ~ AY ;t ^7% V -A '*** U3. l K fit* f absence of anv s>\normaiity. A grea are clinically encir chest x-ray films pulmonarv functi Affair, another or co oresent themseh. toms of acute, suba Si: ' A case of benig been described. Th from the classic pi bestosis. It is proba jt would appear fro tn the literature. As not recognized be self-limited course therapy. Ic can be having been expose prolonged period o; have taken place r years ago. The cc not only pleural, V the demonstration bestosis must be c encial diagnosis cf pleurisy. Acknowledgment: appreciation to Dr. E. to report his patient. 9b K*? A., Fjgcrs 3: Alveolar walls chickened and ir.nitraced with inflammatory cells. Asbestosis body in center. lungs not involved by the malignancy. Sim ilar patients suffering from seif-limited pleural effusions many years prior to the ' development of a -pieural mesothelioma have been observed among the asbestos miners of South Africa.1* However, the proof of benign asbestos pleurisv has been lacking in these cases. . Ic stands to reason that only a minoriev of the persons exposed to asbestos develop ' mesothelioma as a terminal event. How ever, there seems to be a large group of: persons exposed to the mineral suffering from benign pleural involvement in the R: Se describe ur. caso Esta enfermeebd din;, riisico a'e ia anAvccomo p2rec:a secun . de cajos en hi iiterar. no es habituai;:;<?nce nirr.a. y curse- oce tratamjenso esoecidcr persona q:ie ha es:a largo tiempo. Ta: haber teaido Lisar c: r.1 cAc'.'.ojvno corre: pse-ra! sino puimana. i? asses: os. La ashee. c:agros::cv driere: Sieursiia idicpadca. _ i-aate-ar deer:; a.-. -'C~cne. Ce::e anea: tatneau cA-sicue de procabiemsnt p serr.bierai: d'aores 'T i f NVk ! ASBESTOS PLEURISY Si -iavc tos "iousiv ^ hi. 're his ^gram ;ci5ca. "Eristic pa- ?!ural *stosis of the 1 f i j / ..n:;r2tdv in . Sim;rr::ed :o the Toma i :he ; betr. ! r-eicD nowup cf ucrinz :r. the thence of any significant pulmonary ab,ormtaIity- A great number of such cases .ire clinically entirely asymptomatic. Their x-rav film? appear negative: their ..jpicnarv function tests are norma!, ^.in. another group should be expected jo'present themselves with signs and svmptoms of acute, subacute, recurrent or chron ic unilateral or bilateral pleurisy. Summary case of benign asbestos pleurisv has been described. This disease differs greatly from the classic picture of pulmonary asbestosis. It is probably not as uncommon as It would appear from the sparsity of reports in the literature. Asbestos pleurisy is usually not recognized because it has a benign, self-limited course requiring no specific therapv. It can be suspected in a person having been exposed to this substance for a prolonged period of time. Such contact may have taken place recently or a number of vears ago. The correct diagnosis requires not only pleural, but also lung biopsy for the demonstration of asbestos bodies. Asbestesis must be considered in the differ ential diagnosis of any form of idiopathic pleurisy. Acknowledgment: The author expresses his appreciation to Dr. E. C. McRee for his permission to report his patient. Resumen Se describe tin caso de pieuresia por asbestosis. Esta eni'ermedad difiere grandemente dei cuadro ,:isko de `.a asbestos;?. No :> tan poco mmur, como parecia segtin ia escasez tie informacioncs de casos er. !a iiteratura. La pieuresia asbesiosica no es habituainiente descubiena porque es be- ngr.a. y su curso. que se iirr.ita por si. no requiere tratamiento esoecinco. Puede sospecharse er. ur.a persona oue ha estado expuesta a asbestos por iargo tiempe. Tai contactc puede ser recicnte o haoer :enido lugar c:erto rtumero de a.oos antes. El dlasTiOsvico correctc requiere no kr-i .'-''-a. oieursl sine puimonar par: : " . ;r- de asbestos. La asbesv . ei diagrtestico dirsren . ... - . u . pieuresia idiopacica. Rzscmz L auteur decrit ur cas de oieuresie asoestosicue benigr.e. Cette anection differs crandemen: du tableau ciassique de i'asbestcse puimor.aire. Eile nest probabiement pas aussi exceptionneile qu'ii le sembierait d'apres la rarete aes rapports cans !a Httcrnture. La pleurcsie asbestosique n'est habitueilement pns reconmic parcc qu elle a une evolution benigne. en elle-meme limitce. qui ne necessite pas de traitement specifique. E!Jo peut Hue sv.socctee c'nez une personae avant ere exposee a cette substance pendant une periode de temp? prolongee. L*n tel contact pent avoir pris place recemmer.t ou on certain nombre d'annees auparavant. Le diagnostic correct necessite une bic-psie non seulement pleurale. mais egaiemem putmor.aire. pour ia mise en evidence de corps asbestosiques. L'asbestose doit ecre considerce dans le diagnostic differentiel pour touie forme de pleuresie idiopathique. Z C SAHM E N FAS SUNG Beschreibung eines Failes von beniener Asbestose-Pleuritis. Diese Erkrankung weicht erheblich von dem plastischen Bild der pulmonalen Asbestosis ab. Sie ist wahrscheinlich nicht so ungewohnlich. wie es nach der geringen Zahi von Literacurberichten den Anschein haben konnte. Die Asbestose-Pleuritis wird gewohniich nicht erkanm. weil sie gutartig ist und Dank ihres umschrieoenen Ablaufes keine spezifische Therapie erforderlich macht. Man kann daran denken. bei Personen. die gegeniiber dieser Substanz wahrend einer langeren Zeitspanne exponiert waren. Solche kontakte konnen kiirziich oder auch eine Anzahl von Janren zuvor erfolgt sein. Die korrekte Diagnose erfordert nicht nur eine pleurale. sondern auch eine Lungen-Biopsie turn Nachweis der Asbestose-Korper. Die Asbestose muJS bei der Diffenrential-Diagnose in jeder Form der idiopathischen Pleuritis in Erwagung gezogen werden. References ! Section on Nature and Prevalence. Com MITTEE ON GcCVFaTIONaL DISEASES OF THE'. Chest ;A.C.C.P. "Asbesrosis." Da. Che<t. 45:10/. : 964. . Schepers. C. H.: "D'.ffuse Pulmonary Lesions." The P'ublem! oi Difeter.z-.n: Diag nosis o' :he Chest. 41:155. 1963. 4 Pendergrass, c. ?_: The P-.eum&r. -contosis Problem. Charies C :homas. Speir.gr.eid. 1956. 4 Lvnch. K. M.: Arch. Ir.suu. neai:h. 1955. 5 Castleman. 3. j. ano Kisist. B, ,\.: "Case "-1961. 'A'eeklv Patroioeica! Exercises" '.Vx _ zr.gi. }. y:ea.. 155: 745. l'?5!. 6 3anva:. A. L.: S:mbercuious Disease; jf the Chess. Charies C Thomas. Sprir.er.eid. '.934. ' ?*'*sxn. E. H. and Rubin. >.L: Thor.ici; D:s- Saunders C' .. Philadelphia. Ifol. __ : Tl_pp K. S. and 'a'/lson. ?. \V : "Pri- - .....e--. Mesotheiioma ->: the Pleura." :?6C. u'uZt-TTtwy. H. 3.: "Pleura! Asbestos;'." Amer. ,~--caor.es. 13:5*3. :963. 10 'A'aCNE.R. j. C-. SLEGOS. C. A.. AND MaRCKaNO. "Difruse Pleura: Mesothelioma and .Asbestos E.VDosur? or. the Northwestern. Caoe Province." Sr::. ;. f-iu.x. Med.. IT: 250. :9oC. For reprints, piease write Dr. Eisenstact. 330! Procter Street. Port Arthur. Texas. T I' V .VA ; -TVy' ~ s\mi- Vz&Zt;- yyyiy-W'