Document 2Jo3rwMdJ0zK3B1B96aDGMLYL

R&S 113211 * t bio-medical research document description form 63 68 69 76 Duplicate in all cards: --> year as-1961- File number [Right justify [Numeric only] Author(s), as Last Name FS (No Punctuation) and coden for journal as JAMA preceeded by one blank space 1 AKA/At/n. AC/ZAPPzM j 20 21 nr $fA/r/, a a / 40 41 ___________ 77_______78 l/C- Sub-Index Code 60 61 62 _____ Title of Report; end with space-hyphen-hyphen-space. Follow with Index Terms, separated from each other with comma-space. Avoid other punctuation; do not abbreviate. 1 pzc. avst: -- 21 22 23 24 Source (Journal, Vol., Number, Pages, Date) 12 f /7/ff/Hx " \3,, ff-rT ff?-r 61 62 31 32 Brief Summary 12 10 SUMMARY: 61 62 61 62 63 64 I APPENDIX 3 Thorax, 1978, 33, ly 25 z\.ZZVV Polyvinyl chloride pneumoconiosis1 0000420 A. ARNAUD, P. POMMIER DE SANTI, L. GARBE, H. PAYAN, AND J. CHARPIN From the Clinique de Pneumo-phtisiologie, Hdpital Saints Marguerite, Marseille and the Laboratoirc d'Anatomie Pathologiquc. Hdpital dela Conception, Marseille, France Arnaud, A., Pommier dc Santi, P., Garbc, L., Payan, H., and Charpin, J. (1978). Thorax, 33, 19-25. Polyvinyl chloride pneumoconiosis. A 53-ycar-oId 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 with human lung macrophages in vitro showed that the macrophages engulfed the powder to give a similar ultrastructural appearance. Pneumoconiosis due to polyvinyl chloride (PVC) tuberculin skin test was weakly positive. Sputum was first described by Szcndc 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: 4-19X10V1; chloride (VC) inhalation may be responsible for haemoglobin 13`2 g/dl; leucocyte count 6-6X lO^/l abnormalities of pulmonary function and chest with 40% lymphocytes and 60% neutrophils; radiograph (Lilis et al,, 1975, 1976; Miller et al., platelets 294X109/1; erythrocyte sedimentation 1975; Suciu et al,, 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/J; SGPT 39 U/l. Pulmonary ultrastnicture of a lung biopsy specimen. function tests showed forced vital capacity 3-82 1 Case report (expected value 5-29 I); forced expiratory volume in 1 second 2-32 1 (expected value 3-89 1). 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 31-75/mI/min/ graphic abnormalities (Fig. 1). He gave a history mmHg) (10-7 mmol/min/kPa; 10-6 mmol/min/ of chronic productive morning cough for three kPa). No abnormality was seen on bronchoscopy. yenrs, 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 1968 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. Physical examination was negative. A scratch 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; a few smooth muscle fibres were Supported tit part by the Frtititut NAtioruldc fa Same ct dc fa Rcihenrhc Mtdicalo also seen. 19 " J. 20 A. Arnuud, {', I't'innih-r lie Santi. I.. Garbe, //. 1`ayan. and J. Cluirpir. Fig. 2 Lung biopsy showing diffuse infiltration with histiocytes. (Haetnatoxylin and eosin X3S) I R&S 113213 Polyvinyl chloride pneumoconiosis Fig. 3 ' dumps of histiocytes end some giant celts showing a finely vacuolated cytoplasm. ELECTRON MICROSCOPY The specimen was fixed with 3-4% giutaraldehydc 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 ultramicrotome, then stained with uranyi acetate and lead citrate. Examination and photographs were obtained by Philips EM 300 electronic microscope. The cytoplasmic membrane of the macrophages hud 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 size 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 37-5C in a mixture of 20% of compound 1991 and 80% of fetal calf serum1. The macrophages were then treated and examined with the electron microscope according to the method previously described. The absorption of the PVC panicles 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 microfilaments, and multiple lysosomes. Electron microscopy of PVC powder Discussion The PVC powder' was composed of oval grains, whose size varied from O-5X0-3 to 1X0-3 microns. In this case of discrete pulmonary fibrosis associ- `ATCOVYLU, Pcchincy, 04 Saint Auban, Franco Mnilitul paiteur, 75 Paris, France R&S 113215 i // Fig. 4 Histiocyte with a small eccentric nucleus (N); the,cytoplasm is mostly occupied by irregularly outlined phagosomes containing a fluffy granular substance. Collagen fibres (C)- (M X13 900) Fig. 5 Biopsy specimen; fluffy material with irregular outlines surrounded by a dense membrane ("). Phagosomes ere confluent in places (*-). (EM X37 COO) Polyvinyl chloride pneumoconiosis 23 Fig. 6 PVC powder made of oval subunits of variable size; they are linked together by smaller particles (*-). {EM X46000) Fig. 7 In-vitro 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 X37000) ated with a granulomatous reaction the lesions contained particles which could not be 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 al. (1970), who reported the case of a 31-year-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 are the same as those experimentally pro voked by Frongia et of. (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 multinucleated cells. These cells con tained minute intracytoplasmic granules, which were not stained by the usual methods. On later examination, these lesions became focal granulo- 24 .4. Arnaud. P. Pomtnicrdc Santi, L. Garhe, H. Payan, and J. Churpin Fig. 8 In-vitro study of an alveolar macrophage in contact with PVC for90 minutes. Particles of PVC are accumulated in a phagosome, which occupies almost all of the cytoplasm (--X Smaller phagosomes engulf oval corpuscules and small granules of PVC. 0EM xmo) 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 FVC 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 yet of much functional significance; on the other hand, Szende and co-workers (1970) reported a case with severe respiratory impairment. Occupa tional exposure to PVC dust may have been dif ferent in these two cases. Our patient was exposed to PVC dust only, while Lilis et at. (1975, 1976) showed that PVC dust inhalation induced less severe respiratory function abnormalities than simultaneous inhalation of vinyl chloride monomer and PVC. This must be compared with the results described by Prodan et al. (1975), who showed that, in the guinea-pig, two hours' inhalation each day of air containing 10% vinyl chloride monomer over two weeks could produce diffuse pulmonary fibrosis. Further studies of the mechanisms of this pneumoconiosis are in progress. We thank Dr. Allan Towne and Dr. Christian Capo for their help. References Frongia, N.. Spinazzola, A., and Uucarcili. A. (1974). Lesion! polmonari sperimentali da inalazione prolungata di PVC in ambiente di lavoro. Medicina del Lavoro. 65, 321-342. Lais, R., Anderson, H., Nicholson. W. J.. Daum, S,. Fischbein, A. S., and Selikoff, 1. I. (1975). Prcva- R&S 113217 VS'M.mw Polyvinyl chloride pneumoconiosis 25 lcnco of disease among vinyl chloride and poly. I chloride workers. Aimak n( the New York demy of Sciences, 246. 22-41. l.ilis, R.. Anderson, 11., Miller, A., and SelikofT, I. J. (1976). Pulmonary changes among vinyl chloride polymerisation workers. Chest, 69, 299-303. Miller, A., Tirxtcin. A. S._ Cliuang, M., Selikoff, I. J,, 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, 246, 42-52. Prodan, L., Suciu, I., Pislaru, V,, Ilea, ., 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 Annul. of the AVtc York Academy of Sciences, 246, 53-69. Szende, B,, Lapis. K,, Nemes. A., and Pinter, A. (1970). Pneumoconiosis caused by the inhalation of polyvinvl chloride dust. Medicines del Lavoro, 61, 433-436. Requests for reprints to: Dr. A. Arnaud, HApital Sainte Marguerite. BP29-13274, Marseille Cedex 2, France. R&S 113218 c