Document rxb46g2m13j72pyjQVmLQxjLG

Thorax, 1978, 33, 19-25 Vi 1 aorta ,lt with uption. le and arious on the s may counts e descrfect Polyvinyl chloride pneumoconiosis' A. ARNAUD. P POMMIER DE SANTI. L GARBE, H. PAYAN, AND J CHARPIN From the Clinique de Pneumn-phtisiologie. Hopiial Sainte Marguerite, Marseille and the Laboratoire d'Anatvmte Pathologique. Hopiial de la Conception, Marseille, France Arnaud, A., Pommier de Santi, P., Garbe, L., Payan, H,, and Charpin, J. (1978). Thorax, 33, 19-25. Polyvinyl chloride pneumoconiosis. A 53-year-o)d man, who had been exposed for 23 years to polyvinyl chloride (PVC) in the bagging area of a vinyl chloride polymerisation plant, presented with a diffuse micronodular infiltrate on his chest radiograph. Light microscopy of lung obtained by drill biopsy showed a diffuse infiltration with histiocytes and multinucleated giant cells, with some collagen formation. Ultrastructural studies showed foreign particles in the macrophages, which were identical with PVC powder viewed under the electron microscope. Incubation of PVC powder w ith human lung macrophages in vitro showed that the macrophages-engulfed the powder to give a similar ultrastructural appearance. i1j*f4'Ji A.j : v 'Vi k > *-rtr:? fjai fector. niver- Pneumoconiosis due to polyvinyl chloride (PVC) tuberculin skin test was weakly positive. Sputum was first described by Szende et at. (1970). Several examination for Mycobacterium tuberculosis on epidemiological studies have since been made, three specimens was negative. which tend to demonstrate that PVC or vinyl The red blood cell count was: 4I9XI0"/I; chloride (VC) inhalation may be responsible for haemoglobin 13 2 g/dl; leucocyte count 6 6X 10"/1 ' abnormalities of pulmonary function and chest with 40% lymphocytes and 60% neutrophils; radiograph (Lilis cr pi.. 1975, 1976 Miller et al, platelets 294XI0"/I; erythrocyte sedimentation 1975; Suciu et ul. 1975). However, histopatho- rate 6 and 20 mm/h; cholesterol 2 11 g/1; total ., logical descriptions of this disease are infrequent. bilirubin 6 mg/1, serum alkaline phosphatase 53 We describe here one such case and a study of the U/l; SGOT 25 U/l; SGPT 39 U/l. Pulmonary ultrastructure of a lung biopsy specimen. function tests showed forced vital capacity 3 82 1 (expected value 5 29 Deforced exniratnrv volume Case report in 1 second 2 32 1 (expected value 3 89 IV Arterial blood gases: Pao. 84 mmHg: Paco, 40 mmHg; A 53-year-old man was referred in April 1974 for pH 7 39 Carbon monoxide transfer factor 32 14 investigation of diffuse micronodular chest radio- ml/min/mmHg (predicted value 3! 75/ml/min/ graphic abnormalities (Fig. I). He gave a history mmHg) {10-7 mmol/min kPa; 10 6 mmol/min/ of chronic productive morning cough for three kPal No abnormality was seen on bronchoscopy. years, and for three months he had noticed mild A lung biopsy using Steel's pneumatic trephine was weakness and slight exertional dyspnoea. He had performed. smoked 20 cigarettes a day since age 22. The patient had worked from November 1945 . until December 1968 in the PVC bagging area of a vinyl chloride polymerisation factory. Since 1969 he had worked as a shepherd A chest radiograph performed in 196S as a routine factory check-up showed the same micronodular shadows. No fur ther investigations were done. Previous chest ( radiographs were said to have been normal. .^'.bf.ich, P.h-ysi.c.a..l....e..x..a..m...ination was neejtive. A scratch fr 'nr" ' ` " V S. pjvncU in part bs ibe (nvtaut SimmJ U< S.nlc et at U * Recherche M*du:ale LIGHT MICROSCOPY The lung specimen was, for the most part, diffusely infiltrated by histiocytes, in which were seen a few alveolar ducts (Fig 2). The cytoplasm of these histiocytes contained clear vacuoles. Giant multi nucleated cells with vacuolated cytoplasm were also present (Fig. 3). PAS and alcian blue stains were, negative Polarised light revealed no intra vascular birefringent particles The cells were arranged in a collagen matrix, which was of thinly fibrillar aspect; u few smooth muscle fibres were also seen 19 f*\ ir <*) A 3 DTH 00004343:. > ` ll yf/4. Arnaud. P. Pommier de Santi, L. Garhe. H. Payan. and J. Charpin 'V-* . i -; Fig 3 n-.. - V ? \ i t i.- >i \ ELECTRON Mil The specime. in a cacochh. osmium-tetro hydrated in The section microtome i lead citrate obtained by l' . The cytor! had thin exy chromatin * dumps in t nuclear met' major pari, irate rial sun brane, whose was either gi granules wei and 5). Bet* layers cover, were small r The Golgi sv Electron mil The PVC r> whose size v. AFCOVYU h DTH 000043432 ............... Polyvinyl chloride pneumoconiosis 21 Fig. 3 Clumps of histiocytes and some giant cells slmwing a finely vacuolated cytoplasm. ELECTRON MICROSCOPY The specimen was fixed with 3-4% glutaraiiJehyde in a cacodylate buffer; post-fixation was with 2% osmium-tetroxide. The specimen was then de hydrated in acetone and embedded in Araldite. The sections were cut by a Reichert ultra microtome, then stained with uranyl acetate and lead citrate. Examination and photographs were obtained by Philips EM 300 electronic microscope. The cytoplasmic membrane of the macrophages had thin expansions; the nuclei were small, and chromatin was either irregularly disposed in clumps in the cytoplasm or placed against the nuclear membrane. The cytoplasm was. for the major part, infiltrated by a non-homogenous material surrounded by an electron dense mem brane, whose outlines were irregular. This material was either granular or of a fluffy appearance; the granules were 0 3 to 0 4 microns in size (Figs 4 and 5) Between the phagosomes, thin cytoplasmic layers covered the organelles; the mitochondria were small in sire and had well conserved cristi. The Golgi system was normal. These grains were connected by PVC bridges or by the interposition of smaller granules of 0 1 micron diameter (Fig. 6). Phagocytosis of PVC powder by alveolar macrophages Human alveolar macrophages were obtained by bronchial lavage. About 2 to 3X10" macrophages were incubated with 0 2 ml of PVC powder for 90 minutes at 37 53C in a mixture of 20% of compound 199- and 80% of fetal calf serum-. The macrophages were then treated and examined with the electron microscope according to the method previously described. The absorption of the PVC particles in the cytoplasm of these cells was rapidly accomplished. The particles appeared in the phagosomes as either oval corpuscules or clusters which were variable in size (Figs 7 and 8). At this stage, the particles showed no evidence of degradation. Thinly granular lysosomal material was deposited against them. The cytoplasm of the macrophages contained mitochondria, bundles of microlilaments. and multiple lysosomes. Electron microscopy nf PI C powder The PVC powder* was composed of oval grains. whose sire varied fr-m o 5 o t |0 | n t microns 'AFCOVYU:, HciJjHiey, tu Sjint Aubjn, France Discussion In tins case of discrete pulmonary fibrosis associ- Insiitut Fjxicur, 75 !\ins, France I > ; s* -r* ti Fig. 5 Biopsy specimen; fluffy material with irregular outlines surrounded hv a dense membrant ('.Z ). I'hagosumes are confluent in places ( . I. (hM XJ7 000) . ated with contained by the us pneumoo The cl patients > ef of. (H workers < least 20 > chest to lesions corded >' case of . 12 morn DTH 000043434 j Polyvinyl chloride pneumoconiosis 23 Fig. 6 PVC powder made of oval subunits of variable size; they are linked together by smaller particles (_). (EM X46 000) Fig. 7 In-vilro study of PVC particle phagocytosis by an alveolar macrophage showing oval bodies of uneven size with irregular outline, sometimes surrounded by finely granular lysosomal material (--); microfilaments (m F). (EM X 37 000) ated with a granulomatous reaction the lesions contained panicles which could not he identified by the usual stains. We suggest that this may be pneumoconiosis induced by PVC inhalation. The chest radiographic abnormalities in our patients are the same as those described by Lilis et at. (1975); these authors showed that 48 6% of workers exposed in their work to PVC dust for at least 20 years have reticular and/or micronodular chest radiographic .shadows. The histological lesions we describe are identical with those re corded by Szende et at. (1970), who reported the case of a 31-xear-old man who had worked for 12 months in an environment containing high levels of PVC. This patient had severe respiratory failure. Pulmonary biopsy showed diffuse fibrosis associated with focal granulomatous lesions whose cells contained ovoid or polygonal particles. These lesions arc the same as those experimentally pro voked by Frongia et at. (1974), who exposed guinea-pigs and rats from two to seven months in a room where PVC powder was bagged. Exam ination of the guinea-pigs showed an earlier reac tion at alveolar level composed of macrophages and giant multinucleuted cells. These cells con tained minute mtracyloplasmic granules, which were not stained hx the usual methods. On later examination, these lesions became focal granulo- ufc 'J& A 24 /(. Arnaud. P. Pommier de Santi, L. Carbe, H. Payun, and J. Charpin Polyvinyl a r- jj lence of '. vinyl . A cademy Lilij, R,, Ai ], (1976). Pi polymeris. Miller, A., 1 * j and Want i; j tion in v ! chloride. Ll . Sciences, 7 Prodan, L., L. <197? > vinyl chlo Fig. 8 In-vilro studv'&f an alveolar macrophage in contact with PVC for 90 minutes. Particles of PYC are accumulated in a phagosome, which occupies almost all of the cytoplasm ( _V Smaller phagosomes engulf oval corpuscules and small granules of PI C. (EM X6800) c c. i"' t W;. V. A * >% f. Kl y Vi : /, mas. Examination of rats showed more pro nounced initial fibrotic lesions but later lesions were comparable with those observed in the guinea-pigs. The identical morphology of the intracellular foreign particles observed in our patient, and the microscopic appearances of the PVC powder and of the inclusions in human macrophages which have engulfed PVC powder in vitro, are convinc ing evidence that our case can be considered to be that of PVC pneumoconiosis Clinically, the evolution of PVC pneumoconiosis is uncertain. Our patient had only a slight reduc tion in vital capacity with no reduction in gas transfer factor, suggesting that the fibrosis was not as set of much functional significance, on the other hand. Szende and co-workers (I970> reported a case with severe respirators impairment. Occupa tional exposure to PVC dust max have been dif ferent in these two cases Our patient wax exposed to I'VC dust only, while I ills a ul i I*>75. lh7(o showed that PVC dust inhalation induced les severe respiratory function abnormalities thu simultaneous inhalation of vinyl chloride monomer and PVC. This must he compared with the resultl I-5_ described by Prodan et at. (1975), who showed that, in the guinea-pig. two hours' inhalation ead day of air containing 10% vinyl chloride monomaj over two weeks could produce diffuse pulmoi fibrosis. Further studies of the mechanisms of this] pneumoconiosis are in progress. We thank Dr. Allan Towne and Dr. Christie! Capo for their help. References Froneia. N . Spinuiiolu. A., and Itucarelli. A. (1974) , Lt'ioni poltmuiari spcrimeiuali da inalazione p ^ luneala di PVC in ambienle di lawiro. Medicine i I uiora. 65, ? 21 - .'4 2. I ills It., Anderson. II.. Nicholson, \V. Daum, S. iI isilihein. \ S.. and Sclikoll. I. J (I97J). Prev* Jp-.. DTH 000043436 Hi V tfi*"-'*-'-----*- --\ -------mi "harpin i i Polyvinyl chloride pneumoconiosis 25 lence of disease among vinyl chloride and poly vinyl chloride workers. Annals of the New York Academy of Sciences, 246. 22-41. Lilis, R., Anderson, H., Miller, A., and Selikolf, I. J j (1976). Pulmonary changes among vinyl chloride ! polymerisation workers. Chest, 69, 299-303. j Miller, A., Tirstein, A. S., Chuang, M., Selikolf, I. J.. t and Warshaw, I. (1975). Changes in pulmonary func tion in workers exposed to vinyl and polyvinyl chloride. Annals of the New York Academy of * Sciences, 216, 42-52. * Prodan, L., Suciu. 1., Pislaru, V., Ilea, E.. and Pascu, * L. (1975). Experimental chronic poisoning with ; vinyl chloride (Monochloroethene). Annals of the New York Academy of Sciences, 246, 159-163. Suciu, I., Prodan, L., Ilea, E., Paduraru, A., and Pascu, L. (1975). Clinical manifestations in vinyl chloride poisoning. Annals of the New York Academy of Sciences, 246, 53-69. Szendc, B., Lapis, K., Ncmcs, A., and Pinter, A. (1970). Pneumoconiosis caused by the inhalation of polwinvl chloride dust. Medicina del Laioro, 61, 433-436. Requests for reprints to: Dr. A. Arnaud, Hopital Sainte Marguerite, BP29-13274, Marseille Cedex 2, France. t 1 ! 1 i ) i i i !