Faculty Bibliography

The pneumoconioses, interstitial lung disorders resulting from the inhalation of inorganic dusts, are associated with chronic inflammatory processes in the lower respiratory tract. To characterize these inflammatory processes in relation to the pathogenesis of these disorders, we studied 39 nonsmoking individuals with long-term occupational exposures to inorganic dust and functional evidence of interstitial disease (asbestosis, n = 18; coal workers' pneumoconiosis, n = 15; silicosis, n = 6). In all 3 disorders, the inflammation was dominated by alveolar macrophages. Because a common feature of these interstitial lung diseases is concurrent injury and fibrosis of alveolar walls, we assessed whether these alveolar macrophages were spontaneously releasing mediators capable of giving rise to these changes. Alveolar macrophages from the study population were spontaneously releasing increased amounts of superoxide anion and hydrogen peroxide (both p less than 0.01 compared to normals), oxidants capable of injuring lung parenchymal cells. The alveolar macrophages were also spontaneously releasing significantly increased amounts of fibronectin and alveolar macrophage-derived growth factor (both p less than 0.01 compared to normals), mediators that act synergistically to signal fibroblast replication. Taken together, these findings define a major role for the alveolar macrophage in mediating the alveolar wall injury and fibrosis that characterize the common pneumoconioses and suggest that the alveolar macrophage is an important 'target' for developing strategies designed to prevent loss of lung function in these individuals

Idiopathic pulmonary fibrosis is a fibrotic lung disease characterized by an increased number of mesenchymal cells in the alveolar walls. Alveolar macrophages constitutively express low levels of c-sis, the protooncogene coding for the B chain of platelet-derived growth factor, a protein with chemotactic and mitogenic activity toward mesenchymal cells. We therefore hypothesized that alveolar macrophages in patients with idiopathic pulmonary fibrosis may release increased amounts of platelet-derived growth factor, which might help to explain the accumulation of mesenchymal cells and the fibrosis of the lower respiratory tract in the disease. Evaluation of alveolar macrophages recovered from the lungs of patients with idiopathic pulmonary fibrosis demonstrated that these cells spontaneously released four times more platelet-derived growth factor than did alveolar macrophages recovered from normal persons (P less than 0.01). That the platelet-derived growth factor molecules were potentially active was shown by their chemotactic activity for smooth-muscle cells and their ability to act as a 'competence' factor for fibroblast growth. These observations suggest the possibility that the accumulation of mesenchymal cells within the alveolar walls in patients with idiopathic pulmonary fibrosis may result partly from the exaggerated release of the potent mitogen platelet-derived growth factor by mononuclear phagocytes in the lower respiratory tract

Although acute tropical pulmonary eosinophilia (TPE) is well recognized as a manifestation of filarial infection, the processes that mediate the abnormalities of the lung in TPE are unknown. To evaluate the hypothesis that the derangements of the lower respiratory tract in this disorder are mediated by inflammatory cells in the local milieu, we utilized bronchoalveolar lavage to evaluate affected individuals before and after therapy. Inflammatory cells recovered from the lower respiratory tract of individuals with acute, untreated TPE (n = 8) revealed a striking eosinophilic alveolitis, with marked elevations in both the proportion of eosinophils (TPE 54 +/- 5%; normal 2 +/- 5%; P less than 0.001) and the concentration of eosinophils in the recovered epithelial lining fluid (ELF) (TPE 63 +/- 20 X 10(3)/microliter; normal 0.3 +/- 0.1 X 10(3)/microliter; P less than 0.01). Importantly, when individuals (n = 5) with acute TPE were treated with diethylcarbamazine (DEC), there was a marked decrease of the lung eosinophils and concomitant increase in lung function. These observations are consistent with the concept that at least some of the abnormalities found in the lung in acute TPE are mediated by an eosinophil-dominated inflammatory process in the lower respiratory tract

From 1973 to 1974, a longitudinal study of pulmonary function in 113 Utah copper smelter workers reported significant declines in FVC and FEV1 related to sulfur dioxide exposure. In 1980, we performed a 7-yr follow-up study, finding significant increases in FVC and FEV1. The 66 follow-up participants were similar to those 47 lost to follow-up with regard to age and initial pulmonary function. Subgroups of smelter workers with initial higher exposures to sulfur dioxide and FEV1 less than 90% predicted did not show an accelerated rate of decline. To reconcile these differences between the 2 studies, we reevaluated the spirometry curves from 1973 and 1974. All had short expiratory times, with none 6 s or longer, whereas all of the curves from the spirograms obtained in 1980 exceeded 6 s. In addition, from 1980 to 1983, we performed a longitudinal study of 48 of the original workers, finding small annual mean declines for FVC of 6 ml and FEV1 of 5 ml. Personal exposures to sulfur dioxide were not significantly different in 1982 than in 1976; thus, we were unable to corroborate the findings of the initial longitudinal study

Refrigeration repair workers may be intermittently exposed to fluorocarbons and their thermal decomposition products. A case of peripheral neuropathy (distal axonopathy) in a commercial refrigeration repairman prompted an epidemiological investigation of the health of refrigeration repair workers. No additional cases of peripheral neuropathy were identified among the 27 refrigeration repair workers studied. A reference group of 14 non-refrigeration repair workers was also studied. No differences were noted between groups for the ulnar (motor and sensory), median (motor and sensory), peroneal, sural, or tibial nerve conduction velocities. Refrigeration repair workers reported palpitations and lightheadedness significantly more often than workers in the reference group. No clinical neurological or electroneurophysiological abnormalities were detected in eight refrigeration repair workers followed up for three years during continuous employment

Circulating immune complexes, rheumatoid factor, and antinuclear antibodies were evaluated in 25 asbestos insulation workers and 32 brick mason controls. There were 10 asbestos workers with radiographic parenchymal or pleural changes, consistent with their asbestos exposure. There were no differences in antinuclear antibodies or rheumatoid factor between asbestos workers and controls. The asbestos workers had significantly increased levels of IgG and IgA circulating immune complexes. There was a significant correlation between IgA circulating immune complexes and radiographic changes

Naturally occurring zeolite minerals are aluminum silicates widespread in the earth's crust. Several of these minerals have fibrous forms and have been implicated as a possible cause of benign and malignant diseases of the lung and pleura in Turkey. This report describes a patient, living in an area of Nevada rich in zeolites, who presented with idiopathic pleural thickening and pulmonary fibrosis associated with extensive pulmonary deposition of zeolites

Twenty-two underground coal workers with 27 or more years of coal dust exposure were studied with gallium-67 citrate (Ga-67) imaging. Radiographic evidence of coal workers pneumoconiosis (CWP) was present in 12 subjects. The Ga-67 scan was abnormal in 11 of 12 with, and 9 of 10 without, CWP. The Ga-67 uptake index was significantly correlated with total dust exposure (p less than 0.01) and approached significant correlation with the radiographic profusion of the nodules (0.10 greater than p greater than 0.05). There was no correlation between Ga-67 uptake and spirometric function, which was normal in this group of patients; furthermore, increased lung uptake of gallium did not indicate a poor prognosis in subjects no longer exposed to coal dust. While coal dust exposure may be associated with positive Ga-67 lung scan in coal miners with many years of coal dust exposure, the scan provided no information not already available from a careful exposure history and a chest radiograph. Since Ga-67 scanning is a relatively expensive procedure we would recommend that its use in subjects with asymptomatic CWP be limited to an investigative role and not be made part of a routine evaluation

The health status of 325 oil shale workers employed at the Anvil Points, Colorado, demonstration facility from 1948 to 1969 was evaluated. As a comparison population, 323 Utah coal miners frequency matched for age were studied. The prevalence of respiratory symptoms among oil shale workers who smoked were similar to the coal miners who smoked, although nonsmoking oil shale workers had fewer symptoms compared to nonsmoking coal workers. Four cases of skin cancers were found on the oil shale workers and eight cases in the controls. Similar numbers of nevi, telangiectasiae, possible pitch warts, pigment changes (solar/senile lentigo), and papillomata (seborrheic keratoses and skin tags) were seen in both groups, while actinic keratoses were more frequent in the oil shale workers. The prevalence of actinic keratoses was significantly associated with oil shale work after allowing for age, sun exposure, and other exposures. The prevalence of pulmonary cytology metaplasia was associated with years of production work in oil shale among both smokers and exsmokers. More of the oil shale workers had atypical cells in the urine, but the excess was mostly found among exsmokers. Although these workers had short-term and limited oil shale exposure work exposure, we recommend that medical surveillance of oil shale workers consider the skin, respiratory, and urinary systems for special observation