Document 8ynZR4B9vjbg05aL4k6qnD25

BE fciVED 7tzf/k- i1 ti _ Tftorax, 1978,33, 19-25 J T. BARR 7$-a fax. 'll J Polyvinyl chloride pneumoconiosis1 * COS*) (TlUtV U~ A. ARNAUD, P. POMMIER DE SANTI, L. GARBE, H. PAYAN, AND J. CHARP1N From the Clinique de Prteumo-phtisiologie, Hdpt'tal Sainte Marguerite, Marseille end the Lebaratoirt d'Anatomie Pathologique, ffdphol de la Conception, Marseille, France Arnaud, A., Pommier de Sanll, P., Garbe, L., Payan, H., and Charpln, J. (1978). Thorax, 33, 19-25. Polyvinyl chloride pneumoconiosis. A 53-year-old 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 colls, with some collagen formation. UUrastructural 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 Jo polyvinyl chloride (PVC*) ~ tuberculin skin test was weakly positive. Sputum was fba described by Szcnde et a). (1970). Several examination for Mycobacterium tuberculosis on epidemiological studies have since been made, three specimens was negative. which lend to demonstrate that PVC or vinyl The red blood cell count was: 4-I9X10"/!; chloride (VC) inhalation may be responsible for .haemoglobin 13'2 g/dl; leucocyte count 66X10"/! abnormalities of pulmonary* function and chest with 40% lymphocytes and 60% neutrophils; radiograph (Lilis er at.. 1975, 1975; Miller ex al., platelets 294X10V1; erythrocyte sedimentation 1975; Suciu et at., 1975). However, lustopatho- rale 6 and 20 rom/h; cholesterol 2*11 g/l; total logical descriptions of this disease are infrequent. bilirubin 6 mg/I: serum alkaline phosphatase 53 We describe here one such case and a study of the U/l; SCOT 25 U/l; SGPT 39 U/l. Pulmonary ulirastructurc of a lung biopsy specimen. function tests showed forced vital capacity 3*B2 1 (expected value 5*29 1); forced expiratory volume Case report in 1 second 2-82 1 (expected value 3-89 1). Arterial Mood gases: Pao, 84 mmHg: PaC0j 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 mt/min/mmHg (predicted value 31-75/ml/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 bronchdscopy. 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 1988 in the PVC bagging area of a vinyl chloride polymerisation factory. Since 1969 he had worked as a shepherd. A chest radiograph performed in 1963 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 MICftOSCOFY 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 dear vacuoles. Giant multinucleated 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 Snppurud In part by the Imildt National dc to Semi cl Jc to Rccbcrche Midleato also seen. if fofoTlAi-V?- AP00007653 frS9Z0000dV PfJyrinyl chloride fmcumocomosii 21 Fig. 3 Clumps of hhdoeytes mfsome giant cells shotting a finely vai uolated cytopleutt. LLECTRON MICROSCOPY The specimen was fixed with 3-4% glutaraldehyde in a cacodylate buffer; post-fixaiion was with 2% osmium-tetroxide. The meuiimi was then de hydrated in acetone and embedded in ArakJite The sections were cut by a Reichert uferamtcrotorae, then stained with unn\i acetate and lead citrate. Examination and photographs Mere obtained by Philips EM 300 electronic microscope. The cytoplasmic membrane of the macrophages had thin expansions; the nude! 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. Tim material was either granular or of a fluffy appearance: the granules were 0-3 to 04 microns hr 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). P/iotforvros/f of PVC powder by alveolar macrophases Human alveolar macrophages were obtained by bronchial lavage. About 2 to 3X10n macrophages were incubated with 02 ml of PVC powder for 90 minules at 37-5cC in a mixture of 20% of compound 199- and ?0% of fetal calf serum'-1. The macrophages were then treated and examined with the electron microscope according to fhe method previously described. The absorption of the PVC particles in the cytoplasm of these cells was rapidly accomplished. The particles appeared n the phagosomes as either oval corpuscules or clusters which were variable in size (FigsT arid 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 microfilamems. and multiple lysosomes. "Electron microscopy of PVC pokier The PVC powder1 was composed of osal.graim. whose size varied fioni'04KO3 to I XO-j'mfcnms. 'AFCOVyi*, Fatbitwy. 04 Saint AiAun.YWe DfectissJoa - In this case of discrete pulmonary fibrosis assoti- 'Inrtliut Parftvr, 7$ Pirli, Franca AP00007656 AP00007657 24 A. Arnoud. P. Pommitr dv Santi, L, Garbe, H. Paycw, and J. Charptn .jtrficAi TKIS ?A> W4< V :.ir; %.---- _> *&*. [ Fijf. 8 In-vitro study of on alveolar macrophage in contort with PVC for 90 minutes. Panicles of PVC ere accumulated in a phagosome, which occupies almost ail of the cytoplasm (--\ Smaller phagosome* engulf oval corpuscule* and small granule* of PVC. (EM y.680 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 jet of much Functional significance; on the other hand, fraende 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 Lilt's et at. 11975, 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 a!. (1975). who showed that, in the guinea-pig. two hours' inhalation each day of air containing 10"'6 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.. SptnaZ2ola. A., and Bucarclli. A. (1974). Lesion! polmonari sporimenlali da inalazione prolungata di PVC In arribienle di lavoro. Medieina del Lovoro. 65,321-342. Lilts. R.. Anderson. H.. Nicholton. W. J.. Daum, S,, Fiichbein. A. S.. and Sclikoff. I. J. (1975). Prtva- AP00007658 AP00007659