Vinyl chloride and polyvinyl chloride exposure and occupational lung disease.

S everal recent reports,12 and one in this issue (see page 828), have contributed new observations on pulmonary disease in vinyl chloride (VC ) -and polyvinyl chloride (PVC) -exposed patients. Earlier reports, a few even preceding the identification in 1974 of vinyl chloride as a human carcinogen (with hemangiosarcoma of the liver the marker tumor, but most probably not the only tumor), had centered on the rather unexpected occurrence of roentgenographic abnormalities&o or pulmonary function impairment,3’71#{176} or had indicated dyspnea as a prominent symptom9” in VCand/or PVC-exposed workers. The roentgenographic pattern described was essentially that of reticular-linear and/or nodular (small rounded) opacities, involving both lungs, predominantly in the lower zones. Pulmonary function abnormalities, both restrictive and obstructive dysfunction, have been observed, with diffusion defects 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 /ibrosis associated with a granulomatous reaction. Electron microscopic examination showed the giant multinucleated cells to contain a nonhomogenous material in their cytoplasm, which was identified to be PVC. A similar pattern was reproduced by incubation of human macrophages obtained by bronchial lavage, with PVC powder: absorption of PVC particles in the cytoplasm was rapid, with thinly granular lysosomal material deposited against the PVC particles. Similar histologic lesions had been previously described in a human case3 and in an experimental study in guinea pigs and rats.12 Exertional dyspnea, diffuse micronodular chest roentgenographic abnormalities, and restrictive pulmonary dysfunction were the main characteristics in the case of PVC pulmonary fibrosis associated with granulomatous lesions.’ Experimental intratracheal administration of PVC dust in rats’3 has been shown to result in an increase in the activity of lysosomal enzymes, interstitial fibrosis, and granulomatous lesions surrounded by fibroblasts, reticulin, and collagen fibers. An epidemiologic study of a large group of PVCand VC-exposed workers2 detected 20 cases of “typical pneumoconiosis,” ie, chest roentgenogram changes consisting of irregular opacities or micronodular shadows of at least class 1 profusion, according to the ILO U/C classification. All these cases were found among PVC-exposed employees. The pattern of roentgenographic abnormalities described 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 capillaries of hands and fingers, liver and spleen capsular fibrosis, liver fibrosis, abnormalities of the sinusoidal vessels in the liver, and portal hypertension, Ward et al’4 investigated the immunologic status of 58 workers from a VC polymerization plant. The findings included hyperimmunoglobulinemia, cryoglubulinemia, cryofibrinogenemia, in vivo complement activation via the classic pathway, with C4 and C3 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 deposition on vascular endothelium and occlusion of small vessels. In areas with subintimal proliferation