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id the Thorax, 1978,33, 19-25 -1' have t%a. .eh rc- rublcm dies in i by C 1 aorta It with uplion. le and . arious on the s may counts e des erfect Polyvinyl chloride pneumoconiosis' A. ARNAUD. P POMMIER DE SANTI, L. GARBE, H. PAYAN, AND J CHARP1N From the Clinique de Pneumo-phtisiologie, Hopital Sainte Marguerite, Marseille and the Laboratoire d'A natomie Pathologique, Hopital 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-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 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. rector. 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; 4 19XI0-/I; t , chloride (VC) inhalation may be responsible for haemoglobin 13 2 g/dl; leucocyte count 6-6X10V1 " ' abnormalities of pulmonary function and chest with 40% lymphocytes and 60% neutrophils; radiograph (Lilis et pi.. 1975, 1976; Miller et a!. platelets 294X10!'/I; erythrocyte sedimentation ' 1975; Suciu et a!.. 1975). However, histopathc- 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 hiopsv specimen. function tests showed forced vital capacity 3 82 1 Case report (expected value 5 29 1)^ forced expiratory volume in 1 second 2-82 1 (expected value 3 89 I). 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/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 kPa). 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 f radiographs were said to have been normal. vhich Physical .examination was negative. A scratch ' f- - f Tir- ' ' " v 'Sup^yrteU in pari b> the Inailut Njiicinjl de Ij Sente ei de le $ Rirv^crche Mtdicale 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 fihres were also seen 19 ------ - .'.___ ~T- .;' -.' -- - -------- `itii*--'gL"--r--' -*" ^ -'- --r "- ~ - - 20 A Arnaud, P. Pommier de Santi, L. Carbe. H. Pavan. and J. Charpiti ^ Polyvinyl chi p,--? f ; r' **_ '} T.- r? V-- M Fig. 1 Chest radiograph showing diffuse p-~ micronodular infiltrate. .* -r -tr !:- Ft R. , ' t ,^ Fie. 2 Lutu* biopsy shim mu diffuse mfn'trafion with iu^tunytts. (ffartnataxvlin and rosin * .M) 1. ' . >- -). ' r >3 < .Fig. 3 i - e. V*ih :/ *' / r- *rv,, o; ;:* ELECTRON MM The sped me i in a cacod\L osmium-tetri i hydrated in The section microtome, i lead citrate obtained by l` ; The cytop! had thin exp chromatin v clumps in i; nuclear men major part, material sun brane, whose was either gi granules wei and 5). Betw layers cover, were small n The Golgi s> Electron mu The PVC pwhose size n AFCOVYLn i*. DTH 000042444 Polyvinyl chloride pneumoconiosis 21 ELECTRON MICROSCOPY The specimen was fixed with 3 4% glutaraiJehyde 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 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 04 microns in size (Figs 4 and 5) Between the phagosomes, thin cytoplasmic layers covered the organelles; the mitochondria were small in si/e and had well convened cristi. The Golgi system 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 02 ml of PVC powder for 90 minutes at 37 5C 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 of PVC powder The PVC powder1 was composed of oval grains. whose si/e variedTr>'in ii s iH io I o 7 microns 'AFCOVYLIi, Pechmej, S-iirw Auhan. France Discussion In this case of discrete pulmonary fibrosis associ- Irisiiiut P^Mcur. 75 Paris, France f- tvr*** : .v. ^V**i$ "Mi .*: ' *e*#w?%y*>f : f7o . Polyvinyl chi ,v\s?l9 '. --'. -i/ .+ .4f *. a. >> -, ^ .7. *w * iC V :v, x- r ; '^' :4r waan j*': i'->S85 ' "-f- -af 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 (O. (EM X13 900) * A '<-.. * ated with ;j ! - contained it- by the us pneumoo Fig. 5 Biopsy specimen; fluffy, s -pj,e c|, material with irregular outlines , ftients i surrounded by a dense membram '1 C.Z ). 1`liagosnnies are confluent j, ' ,n places (. ) (EM X37 000) -I . ^risers < least 20 > chest r.i lesions vv corded F case of . 12 mow 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-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 X 37 000) ated with a granulomatous reaction the lesions contained panicles 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 al. (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-vear-old man who had worked for 12 monihs 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 al. (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 b> the usual methods. On later examination, these lesions became focal granules- 24 A. Arnaud. P. Pommier de Sartti, L. Carbe, H. Pavan, and J. Charpiti Polyvinyl a Sc. t . I fence of ' MiqyLsklu I A cademy *- lilis, R.t Ai * 1. (I97). P> || , polymeris. U. Wilier, A., 1 '.. ] and Warsl . j tion in v t J chloride. ;; Sciences, 2 :.. Prodan, L., 5 i L. (1975) j, vinyl chlo f-l: t %' jk f-r: ' ' i .. i Fig. 8 In-vitro study'&f an alveolar macrophage in contact with PVC for 90 minutes. Particles of PVC are accumulated in a phagosome, which occupies almost all of the cytoplasm (,_). Smaller phagosomes engulf oval corpuscules and small granules of PVC. (EM X6800) ** - 11 f / 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 >et of much functional significance, on the other hand. Szende and co-workers (19701 reported a case with severe respirators 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 I ibs ct u/ i 1975. 197(0 showed that PVC dust inhalation induced li severe respiratory function abnormalities the simultaneous inhalation of vinyl chloride monomtr and PVC. This must be compared with the result! described by Prodan et at. (1975), who showed that, in the guinea-pig. two hours' inhalation ead' day of air containing 10% vinyl chloride monomer] over two weeks could produce diffuse pulmom fibrosis. Further studies of the mechanisms of this k pneumoconiosis are in progress We thank Dr. Allan Towne and Dr. Christiu Capo for their help. References "t Frnneia, N.. Spinaiiolu. A., and Mucarelli. A. (1974) r LcMoni polnuinari spenmeniali dj inalazione pm *: luneata di PVC in ambiente di lauiro. Medicina k 1 / uvoro. 65. 321 -542. I ills R., Anderson, II.. Sichnlsnn. \V. J., Daum, S. 'I iselibe'in. A S.. and Selikoll. I. J. (1975). PrtVI !' C 4 "hatpin i , Polyvinyl chloride pneumoconiosis 25 lence of disease among vinyl Chloride and poly vinyl chloride workers. Annals of the New York Acoilemy of Sciences, 246, 22-41. Lilis, R., Anderson, H., Miller, A., and Selikoif, 1. J. i (1976). Pulmonary changes among vinyl chloride polymerisation workers. Chest, 69, 299-303. j Miller, A., Tirstein, A. S., Chuang. M., Selikoif, I. J.. i and Warshaw, I. (1975). Changes in pulmonary func tion in workers exposed to vinyl and polyvinyl chloride. Annals of the New York Academy of i Sciences, 246, 42-52. | Prodan, L., Suciu. I., Pislaru, V., Ilea, E., and Pascu, j L. (1975). Experimental chronic poisoning with ; vinyl chloride (Nlonochloroethene). Annals of the New York Academy of Sciences, 246, 159-163. Suciu, 1., Prodan, L., Ilea, E., Paduraru, A., and Pascu, L. (1973). Clinical manifestations in vinyl chloride poisoning. Annals of the New York Academy of Sciences, 246, 53-69. Szende, B., Lapis, K., Nemes, A., and Pinter, A. (1970). Pneumoconiosis caused by the inhalation of polyvinyl chloride dust. Medicina del Lavoro, 61, 433-436. Requests for reprints to: Dr. A. Arnaud, Hopital Sainte Marguerite, BP29-13274, Marseille Cedex 2, France. j i itI i ed less s than momer results showed n each momer nonary of this -ristian (1974). ne pro mo del am, S., Preva- t