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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experimental studies on particle-induced pulmonary fibrosis have not provided consistent evidence for the specific induction of fibroblast-regulating cytokines by pulmonary macrophages in response to fibrogenic as compared to non-fibrogenic particles. Using an optimized, wholly serum-free bioassay, we assessed mitogenic activity for pulmonary fibroblasts in supernatants of short-term cultures of alveolar macrophages exposed to either fibrogenic silica or non-fibrogenic titanium dioxide ducts. The responses to these supernatants were influenced by the replicative status of the target cells, in that samples which stimulated non-cycling fibroblasts caused inhibition of DNA synthesis by cycling cells when tested at the same concentration. However, both silica and titanium dioxide elicited comparable secretion of growth factor activity by macrophages, following either in-vitro or in-vivo administration of particles. In contrast, bronchoalveolar lavage fluids from animals that received intratracheal injections of silica, but not from those that received titanium dioxide, exhibited a sustained reduction in fibroblast-stimulating activity. We conclude that secretion of growth factor activity by alveolar macrophages in culture is induced by particles in a non-specific manner. However, alterations in mitogenic activity in bronchoalveolar lavage fluid may constitute a biological marker of the pattern of pulmonary injury which progresses to fibrosis.
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PMID:Mitogenic activity for fibroblasts induced by silica and titanium dioxide particles in vitro and in vivo. 132 13

A short-term toxicological test has been developed using a calorimetric method. The metabolic activity, observed as the heat exchange rate, was monitored from alveolar rabbit macrophages in monolayers exposed to different metal and non-metal particles. Calorimetric activity indices and viability indices were introduced, from which toxic effects could be assessed. Manganese dioxide particles were found to be cytotoxic. In contrast, titanium dioxide particles seemed to be harmless. The results were in accordance with the cell survival found by use of a fluorescein ester staining method and measured by an image analyzer. Toxic effects from quartz in the form of increased metabolic activity of exposed cells could be detected by the calorimeter in contradiction to the use of the image analyzer. This latter result supports the hypothesis that silica particles cause chronic modification of the macrophage function and that this change in the alveolar macrophage function may be the first of a series of processes leading to pulmonary fibrosis.
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PMID:Calorimetry: a new quantitative in vitro method in cell toxicology. A dose/effect study of alveolar macrophages exposed to particles. 150 65

A study was done to examine whether workers exposed to titanium tetrachloride had significantly higher risks of lung cancer, chronic respiratory disease, pleural thickening/plaques, or pulmonary fibrosis than referent groups. A total of 2477 employees from two titanium dioxide plants were studied. Of that group, 969 employees exposed to titanium tetrachloride were observed from 1956 through 1985 for cancer and chronic respiratory disease incidence and from 1935 through 1983 for mortality. A cross-sectional sample of 398 employees was evaluated for chest roentgenogram abnormalities. Cohort analyses showed that the risk of developing lung cancer and other fatal respiratory diseases was not statistically significantly higher for the titanium tetrachloride-exposed workers than for the referent group. Nested case-control analyses found no statistically significant association between titanium tetrachloride exposure and risk of lung cancer, chronic respiratory disease, and chest roentgenogram abnormalities. No cases of pulmonary fibrosis were observed among titanium tetrachloride-exposed employees. Smoking was found to be a strong predictor of lung cancer mortality in the nonexposed employees with an increased risk of dying from lung cancer up to 7-fold higher in current smokers than in nonsmokers.
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PMID:Epidemiologic study of lung cancer mortality in workers exposed to titanium tetrachloride. 159 72

Exposure of phagocytic cells to asbestos in vitro results in an augmented production of reactive oxygen metabolites and increased peroxidation of lipids. The aim of this investigation was to assess the extent of lipid peroxidation both in cells and fluid obtained from bronchoalveolar lavage (BAL), and in lungs of rats exposed to crocidolite asbestos or titanium dioxide (TiO2), a nonfibrous particulate control. In comparison to sham and TiO2-exposed rats, the BAL fluid and cells of crocidolite-exposed animals contained significantly elevated levels of malondialdehyde (MDA), a breakdown product of lipid peroxidation detected using high-pressure liquid chromatography (HPLC). In contrast, no significant differences in MDA were detected in lavaged lung tissue from these animals. Inhalation of crocidolite caused an early inflammatory response characterized by elevated numbers of polymorphonuclear leukocytes and lymphocytes, as well as enhanced total protein in BAL. Pulmonary fibrosis and increased lung hydroxyproline also were observed after 20 days of exposure. Exposure to TiO2 did not cause inflammation, pulmonary fibrosis, or elevated amounts of hydroxyproline in the lung. Our results show that exposure to the fibrogenic and inflammatory mineral, crocidolite, results in an enhanced lipid peroxidation in BAL cells and fluid not observed after inhalation of the particulate TiO2. These novel observations suggest that MDA in BAL may be useful as a biomarker of exposure to inhaled asbestos or other oxidants.
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PMID:Enhanced lipid peroxidation in lung lavage of rats after inhalation of asbestos. 166 39

Studies comparing pulmonary responses to crystalline silica (SiO2) and titanium dioxide (0.3 microns diameter, TiO2-F) demonstrated a positive correlation between alveolar macrophage (AM) release of interleukin-1 (IL-1), tumor necrosis factor (TNF) and fibronectin and, pulmonary granuloma formation, inflammation and fibrosis, respectively. AM IL-1 release was associated with the development of pulmonary granulomas after SiO2 exposure. AM release of TNF positively correlated with the degree of neutrophil recruitment after SiO2 or TiO2-F exposure. A persistent increase in AM fibronectin release consistently correlated with the development of pulmonary fibrosis after SiO2 or TiO2-F exposure. Studies comparing pulmonary responses to ultrafine TiO2 (TiO2-D; particle diameter, 0.02 microns) with TiO2-F demonstrate that ultrafine particles have a relatively greater toxicity on a mass/lung basis. Exposure to TiO2-D resulted in a persistent increase in AM TNF and fibronectin release which was associated with neutrophil recruitment and fibrosis, respectively. TiO2-D did not stimulate AM IL-1 release and this was consistent with the absence of a granulomatous response to TiO2-D. In light of the known bioactivities of IL-1, TNF and fibronectin, these correlative findings suggest that these mediators play significant roles in pulmonary responses to mineral dust exposure and may serve as potential early biomarkers of pulmonary toxicity.
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PMID:Cytokine and growth factor release by alveolar macrophages: potential biomarkers of pulmonary toxicity. 166 54

Rats were exposed for 1 year, with a 2-year follow-up, to dust clouds consisting of a mixture of amosite or chrysotile asbestos with either titanium dioxide or quartz. The addition of titanium dioxide to asbestos did not increase levels of pulmonary fibrosis above the amounts produced by chrysotile or amosite alone. Quartz, however, greatly increased fibrosis above that produced by the asbestos types alone. Both particulate dusts caused an increase in the numbers of pulmonary tumours and mesotheliomas compared to asbestos alone but while tumours in animals treated with asbestos and quartz tended to occur earlier than tumours with asbestos alone, in animals treated with dusts containing titanium dioxide, tumour production occurred later than with asbestos alone. In animals treated with mixtures of asbestos and quartz, there was evidence of increased transport of fibres across the visceral pleural surface and this may be associated with the finding of a higher proportion of pleural mesotheliomas than previously reported in experimental inhalation studies from any laboratory using the main asbestos varieties. The presence of particulate dusts made little difference to the amounts of amosite fibre retained in the lung tissue but, with chrysotile, titanium dioxide appeared to increase retention while quartz reduced it.
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PMID:Experimental studies in rats on the effects of asbestos inhalation coupled with the inhalation of titanium dioxide or quartz. 174 4

The type of lung disease caused by metal compounds depends on the nature of the offending agent, its physicochemical form, the dose, exposure conditions and host factors. The fumes or gaseous forms of several metals, e.g. cadmium (Cd), manganese (Mn), mercury (Hg), nickel carbonyl (Nl(CO)4, zinc chloride (ZnCl2), vanadium pentoxide (V2O5), may lead to acute chemical pneumonitis and pulmonary oedema or to acute tracheobronchitis. Metal fume fever, which may follow the inhalation of metal fumes e.g. zinc (Zn), copper (Cu) and many others, is a poorly understood influenza-like reaction, accompanied by an acute self-limiting neutrophil alveolitis. Chronic obstructive lung disease may result from occupational exposure to mineral dusts, including probably some metallic dusts, or from jobs involving the working of metal compounds, such as welding. Exposure to cadmium may lead to emphysema. Bronchial asthma may be caused by complex platinum salts, nickel, chromium or cobalt, presumably on the basis of allergic sensitization. The cause of asthma in aluminium workers is unknown. It is remarkable that asthma induced by nickel (Ni) or chromium (Cr) is apparently infrequent, considering their potency and frequent involvement as dermal sensitizers. Metallic dusts deposited in the lung may give rise to pulmonary fibrosis and functional impairment, depending on the fibrogenic potential of the agent and on poorly understood host factors. Inhalation of iron compounds causes siderosis, a pneumoconiosis with little or no fibrosis. Hard metal lung disease is a fibrosis characterized by desquamative and giant cell interstitial pneumonitis and is probably caused by cobalt, since a similar disease has been observed in workers exposed to cobalt in the absence of tungsten carbide. Chronic beryllium disease is a fibrosis with sarcoid-like epitheloid granulomas and is presumably due to a cell-mediated immune response to beryllium. Such a mechanism may be responsible for the pulmonary fibrosis occasionally found in subjects exposed to other metals e.g. aluminium (Al), titanium (Ti), rare earths. The proportion of lung cancer attributable to occupation is around 15%, with exposure to metals being frequently incriminated. Underground mining of e.g. uranium or iron is associated with a high incidence of lung cancer, as a result of exposure to radon. At least some forms of arsenic, chromium and nickel are well established lung carcinogens in humans. There is also evidence for increased lung cancer mortality in cadmium workers and in iron or steel workers.
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PMID:Metal toxicity and the respiratory tract. 217 66

Immunogold-silver staining was used to identify T lymphocytes, T lymphocyte subsets, and B lymphocytes in lung tissue from mice injected intratracheally with silica, titanium dioxide, or saline alone. Morphometric quantitation revealed a marked influx of T lymphocytes in the silica-treated animals during the first 3 weeks after injection. The relative numerical density of these cells remained elevated when compared with saline-treated controls throughout the 12 weeks of the experiment. Cells expressing the CD4 and CD8 antigens were both increased in number, with the former accounting for approximately two-thirds of the T lymphocytes. An increased number of B lymphocytes was also apparent from 6 weeks after treatment with silica. The T lymphocyte response preceded the development of significant pulmonary fibrosis by several weeks. No lymphocyte response was observed in the lungs of mice injected with nonfibrogenic titanium dioxide. These observations are consistent with the hypothesis that lymphokines secreted by T lymphocytes play a role in the pathogenesis of silicotic inflammatory lesions and their progression to fibrosis.
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PMID:Quantitative immunohistologic assessment of lymphocyte populations in the pulmonary inflammatory response to intratracheal silica. 255 10

The objective of this study was to determine whether workers exposed to titanium dioxide (TiO2) had significantly higher risks of lung cancer, chronic respiratory disease, pleural thickening/plaques, or pulmonary fibrosis than referent groups. A total of 1,576 employees exposed to TiO2 were observed from 1956 through 1985 for cancer and chronic respiratory disease incidence, and from 1935 through 1983 for mortality. A cross-sectional sample of 398 employees was evaluated for chest roentgenogram abnormalities. Cohort analyses suggested that the risks of developing lung cancer and other fatal respiratory diseases were no higher for TiO2-exposed employees than for the referent groups. Nested case-control analyses found no statistically significant associations between TiO2 exposure and risk of lung cancer, chronic respiratory disease, and chest roentgenogram abnormalities. No cases of pulmonary fibrosis were observed among TiO2-exposed employees.
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PMID:Epidemiologic study of workers exposed to titanium dioxide. 323 Apr 44

A hygiene study of a hard metal factory was conducted from 1981 to 1984. All workers exposed to hard metal were medically examined and their exposure to cobalt measured. Eighteen employees had occupational asthma related to exposure to hard metal, a prevalence rate of 5.6%. Nine had a positive bronchial provocation test to cobalt and reactions of the immediate, late, or dual type were elicited. Exposure measurements suggest that asthma may be caused by cobalt at a mean time weighted average concentration below 0.05 mg/m3. Only two of the nine individuals with cobalt asthma had a positive patch test to cobalt. Chest radiographs of three workers showed diffuse shadows of category 1 or over. X ray microanalysis of lung biopsy specimens from two of these three workers showed the presence of tungsten, titanium, cobalt, nickel, and some minerals. One of the two was diagnosed as having pneumoconiosis due to exposure to silica in a steel industry and the other was suspected of having pulmonary fibrosis caused by dust generated from the carborundum wheels used to grind hard metal. There were no cases with interstitial pneumonitis in the factory.
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PMID:Respiratory diseases in hard metal workers: an occupational hygiene study in a factory. 371 95


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