Document MGdBZjr5OXNQzJ1yB5rq35eDL

R&S 114263 1 . , ^ -'V ^ BIO-MEDICAL*research /DOCUMENT DESCRIPTION FORM 63 68 69 ^1^76 Duplicate.in all cards:--> \ Ltfff 1 <v year as--1961-- File numbex [Right justify [Numeric only] ' Author (s), as Last Name FS (No Punctuation) and coden for journal as JAMA preceeded by one blank space 1 20 21 40 41 N. __ ________ - --------- 7778 I !/- 1 Sub-Index Code 60 51 62 11 12 13 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. 12 ' - : * 61 62 21 . ; 22 --- D iy'dL 23 24 Source (Journal, Vol., Numberj Pages, Date ) *1 62 ~3l" 32 Brief Summary 12 10 SUMMARY: 61 62 61 62 63 64 COMMENTARY This commentary provides editorial perspectives on the report which follows Vinyl Chloride and Polyvinyl Chloride Exposure and Occupational Lung Disease Ruth Lilis, M.D." NOTICE; THIS MATERIAL MAY SE PROTECTED BY COPYRIGHT LAW (TITLE 17, U. S. CODE) --------- 33 fio W -* ^ Several recent reports,1,2 and one in this issue (see page S-S), have contributed new observations on pulmonary disease in vinyl chloride (VC)-and polyvinyl chloride (PVC)-exposed patients. Earlier reports, a few even preceding the identifi cation in 1974 of vinyl chloride as a human car cinogen (with hemangiosarcoma of the liver tire marker tumor, but most probably not the only tumor), had centered on the rather unexpected oc currence of roentgenographic abnormalities^ or pulmonary function impairment,3,710 or had indi cated dyspnea as a prominent symptom9,11 in VCand/or PYC-exposed workers. The roentgenographic pattern described was es sentially that of reticular-linear and/or nodular (small rounded) opacities, involving both lungs, predominantly in the lower zones. Pulmonary func tion abnormalities, both restrictive and obstructive dysfunction, have been observed, with diffusion de fects and arterial desaturation in some cases. - Two recent reports, one a case report,1 the other an epidemiologic survey,2 seem to identify PVC dust as the etiologic agent in a peculiar type of pulmonary fibrosis associated with a granulomatous reaction. Electron microscopic examination showed the giant multinucleated cells to contain a non- -- homogenous material in their cytoplasm, which was identified to be PVC. A similar pattern was repro duced by incubation of human macrophages ob tained by bronchial lavage, with PVC powder: ab sorption of PVC particles in the cytoplasm was rapid, with thinly granular lysosomal material de posited against the PVC particles. Similar histologic lesions had been previously de scribed in a human case3 and in an experimental study in guinea pigs and rats.12 Exertional dyspnea, diffuse micronodular chest roentgenographic abnormalities, and restrictive pul monary dysfunction were the main characteristics in the case of PVC pulmonary fibrosis associated with granulomatous lesions.1 Experimental intratracheal administration of PVC dust in rats13 has been From the Environmental Sciences Laboratory, Mount Sinai School of Medicine, New York. Reprint requests: Dr. Lilis, Environmental Sciences Labora tory, Mt. Sinai School of Medicine, New York City 10029 shown to result in an increase in the activity or lysosomal enzymes, interstitial fibrosis, and granu lomatous lesions surrounded by fibroblasts, reticulin, and collagen fibers. An epidemiologic study of a large group of PVCand VC-exposed workers2 detected 20cases--of "typical pneumoconiosis." ie, chest roentgenogram changes consisting of irregular opacities or micronodular shadows of at least class 1 profusion, accord ing to the ILO U/C classification. All these cases were found among PVC-exposed employees. The pattern of roentgenographic abnormalities de scribed is very similar to that reported in the case in which the lung biopsy specimen revealed fibrosis and granulomatous reaction, with inclusion of PVC particles. The same study reported the presence of less marked roentgenographic abnormalities, of the linear-reticular type, in a much larger proportion (32 percent) of the population examined; these changes were present in VC monomer-exposed and in PVC-exposed employees. While the prevalence was higher in smokers than nonsmokers, 65 of the 388 abnormal x-ray films were found in individuals who had never smoked. This observation is relevant since the pulmonary efFects of vinyl chloride monomer per se are of great interest. In the context of the multiorgan effects of vinyl chloride, including the peculiar syndrome of acroosteolysis, scleroderma-like skin changes, vascular changes affecting the arteries, arterioles, and capil laries of hands and fingers, liver and spleen capsular fibrosis, liver fibrosis, abnormalities of the sinusoidal vessels in the liver, and portal hypertension. Ward et alM investigated the immunologic status of 58 work ers from a VC polymerization plant The find ings included hyperimmunoglobulinemia, cryoglubulinemia, eryofibrinogenemia, in vivo complement activation via the classic pathway, with C* and Cj conversion and an increase in the B cell lymphocyte population. Immunofluorescent examination of skin, muscle, and lung biopsy specimens revealed the presence of circulating immune complexes, with de position on vascular endothelium and occlusion of small vessels. In areas with subintimal proliferation 826 RUTH LILIS CHEST, 78: 6, DECEMBER, 1980 Rid luminal occlusion, there was immunoglobulin, complement, and fibrinogen deposition in the subintimal regions of the vessel wall. The presumed sequence of changes was thought to be structural alteration of protein molecules, as a direct effect of a highly reactive metabolite of vinyl chloride, elicit* ing an immune response, with activation of B cells and hyperimmunoglobulinemia. Cryoprecipitable immune complexes (antigenic altered protein plus immunoglobulin) activate complement, with conse quent vascular occlusion, througli fibrinogen/fibrin conversion and polymerization. Collagen synthesis is stimulated in these ischemic areas. Similar abnonmalities of-the immunologic status were found in another study of 22 workers exposed to vinyl chloride, with Raynaud's syndrome, and in some cases, acroosteolysis. Latent cryoglobulinemia was detected in 18 cases, with increases of immuno globulins, IgA and IgG. Circulating cryoimmunoglobulins are a prominent feature of idiopathic pulmonary fibrosis15 and in creased IgG levels have been shown to be character istic for bronchoalveolar lavage fluid of such pa tients. Interstitial pulmonary fibrosis is a possible effect of vinyl chloride exposure; the occurrence of more dramatic and specific abnormalities in other organ systems--liver, spleen, and peripheral circulationlias probably prevented more focused attention on pulmonary effects of vinyl chloride in the past. Long-term effects of vinyl chloride include welldocumented carcinogenicity. Lung cancer has been found to occur with an increased incidence in sev eral mortality studies.10'18 In experiments on mice, Suzuki13 has described hyperplastic changes of the alveolar lining cells and pulmonary tumors in the majority of exposed animals. The ultrastructure was thought to indicate that the tumors originated in type 2 alveolar cells. Alveologenic tumors were also described in several other experimental studies.20*22 Interestingly, other known carcinogens, such as polycyclic aromatic hydrocarbons, nitrogen mustard, and chromates produce pulmonary tumors in experi mental animals similarly, originating in the type 2 alveolar cell. The effects of vinyl chloridc-nolvvinvl chloride exposure on the respiratory system of exposed work ers seem to indicate two patterns of nonmaJiznant effects: a Rnimilomatousjrcactian. to PVC dust, uyjth inclusion of PVC particles in macrophages and his tiocytes, and associated interstitial fibrosis, and an interstitial pulmonary fibrosis due to vinyl chloride monomer effect on protein molecules and the im munologic mechanisms triggered by the altered pro tein. The long-term carcinogenic effect, with a signifi cant increase in the incidence of lung cancer also is of concern, although the magnitude of this effect has not yet been completely evaluated. References 1 Arnaud A, Ponmiicr de Santi P, Garbo L, et al. Polyvinyl chloride pneumoconiosis. Thorax 1978; 33:19-25 2 Mastrangelo G, Marino M, Marcer G, et al. Polyv inyl chloride pneumoconiosis: epidemiological study of ex posed workers, j Occup Med 1979; 21:540-542 3 Szende B, Lapis K, Ncmes A, et al. Pneumoconiosis' caused by the inhalation of polyvinylchloride dusL Med Lavoro 1970; 61:433-436 4 Lilis R, Anderson 11, Miller A, et al. Pulmonary changes among vinyl chloride polymerization workers. Chest 1976; 69 (Suppl 2):299-303 5 Lilis R, Anderson H, Miller A, et al. Modifications pulmonaires et exposition au chlorure et polychlorure de vinyle. Med Hyg 1977; 35:1542-1545 6 Wegman D. Further results in polyvinyl chloride produc tion workers, discussion. Ann NY Acad Set 1975; 246:1821 7 Miller A, Teirstein AS, Cliuang M, et al. Changes in pulmonary function in workers exposed to vinyl chloride and polyvinyl chloride. Ann NY Acad Sci 1975; 246:4252 8 Berk PD, Martin JF, Waggoner JG.'Persislence of vinyl chloride-induced liver injury after cessation of exposure. Ann NY Acad Sci 1975; 246:70-77 9 Lange CE, Juhc S, Stein G, et al. Die sogenanntc Vinylchloride-Kranheit-einc borugsdebingte Systcmsklerose? Intern Arch Arbeitsmcd 1974; 32:1 10 Walker AE. A preliminary report of a vascular abnormal ity occurring in men engaged in the manufacture of polyvinyl chloride. Br J Dermatol 1975; 93(Suppl 2): 22-23 11 Walker AE. Clinical aspects of vinyl chloride disease; skin. Proc Roy Soc Med 1976; 69:286-290 12 Frongia N, Spinazzola A, Bticarelli A. Lesion! polmonari sperimentali da inahv/.ionc prolungata di polvcri di PVC in Hinhicnte di lavoro. Med Lavoro 1974; 65:321-342 13 Agarwal DK, Kaw JL, Srivastave SP, et al. Some bio chemical and histopaihological changes induced by poly vinyl chloride dust in rat lung. Environ Res 1978; 16: 333-311 14 Ward AM, Udnoon S, Watkins J, ct al. Immunological mechanisms in the pathogenesis of vinyl chloride disease. Br Med J 1976; 1:936-938 15 Crystal RG, Fulmer JD, Roberts WC, et al. Idiopathic pulmonary fibrosis: clinical, histologic, radiographic, physiologic, scintigraphic, cytologic, and biochemical aspects. Ann Intern Med 1976; 85(G):769-788 16 Tabershaw 1R, Galley WIl. Mortality study of workers in the manufacture of vinyl chloride and its polymers. J Occup Med 1974; 16(8):509-518 17 Ott MG, Langner RR, Holder BB. Vinyl chloride expo sure in a controlled industrial environment. Arch Environ Health 1975; 30:333-339 18 Waxwciler RJ, Stringer W, Falk II, ct al. NIOSH--Neo plastic risk among vinyl chloride polymerization workers. Ann NY Acad Sci 1970; 271:40-48 19 Suzuki Y. Pulmonary tumors induced in mice by vinyl chloride monomer. Environ Res 1978; 16:285-301 20 Keplingcr ML, Coodc JW, Gordon DE, "ct al.`Interim CHEST, 78: 6, DECEMBER, 1980 VINYL CHLORIDE AND POLYVINYL CHLORIDE EXPOSURE 827 R&S o>