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Noninvasive detection of early asbestos-related disease of the thorax: algorithmic analysis of radiographic, nuclear, and serologic tests.

Improved imaging techniques may assist in the diagnosis of early asbestosis, such as could occur from "asbestos in place." These include (1) increased visualization of visceral pleural thickening, (2) high-resolution computed tomography (HRCT), and (3) gallium scanning, combined with evidence of serum markers indicating inflammation-associated pulmonary collagen formation. Combining these imaging and serum test observations with a clinically useful algorithmic approach may permit the diagnosis of "early" asbestosis, which is not now possible from the individual test results or from an unweighted combination of such data.

Asbestos↗

Health effects of tremolite. Now and in the future.

Although tremolite asbestos has been well characterized since 1916, appreciation of its role in disease induction is relatively recent. It has always been understood that the morphology of tremolite is complex, and part of the slowness in recognizing it as a hazard has been definitional in nature. Reduced to simple terms the questions are, when is tremolite "asbestos-like," when is it an innocuous amorphous particle, do these forms occur together, with what confidence can they be separated for regulatory purposes, and what is the spectrum of disease potential for varying exposure? A brake on regulation is partially due to a convergence of opinion of unlikely and unintentional allies: industries producing tremolite-containing materials and some epidemiologists resisting attribution of risk to tremolite on the grounds that its known effects--pleural plaques, asbestosis, lung cancer and mesothelioma--are principally due to chrysotile, which is often contaminated with fibrous tremolite. The latter group concentrate their skepticism on internal-dose biomarker studies associating lung tremolite content with mesothelioma (but not so clearly with lung cancer or asbestosis). They ignore the basic carcinogenic quality of fibrous tremolite, shown in both animal and epidemiological studies. Evidence from the Quebec chrysotile/tremolite mining districts suggests that very low concentrations of tremolite in ambient air can be translated into high concentrations in lung, even in those without occupational exposure. Disease incidence, especially for mesothelioma, seems also to be associated with tremolite air and lung content. The risk associated with tremolite has been demonstrated in Corsica, Cyprus, the United States, and Canada. Of particular importance is an apparent increase in the proportion of mesothelioma risk attributable to tremolite, since the fibers heretofore most responsible for that disease--commercial amphiboles--have been or are being severely regulated or completely eliminated in production and use. Further, amosite and crocidolite, while still a concern, form a small fraction of "asbestos-in-place": most of this material is chrysotile and we do not really know to what degree it is contaminated with tremolite. The available evidence suggests that bulk analysis or airborne fiber analysis will not answer this question, and perhaps only animal bioaccumulation assay is sufficient. Until we know more, it seems prudent for public health to avoid dispersing chrysotile/tremolite into the environment, and, where we can, to regulate all tremolite "fibers" conservatively.

Animals↗

Ventilatory decrements in former asbestos cement workers: a four year follow up.

A four year follow up of the ventilatory function in former asbestos cement workers has been performed to determine whether any further decrease occurred after cessation of exposure. Seventy five of 125 subjects were eligible for re-examination and were compared with local referents. None showed signs of asbestosis but 32% had pleural plaques at the renewed examination. Cumulative asbestos exposure calculated as fibre x years had been estimated individually in the original examination. After adjustment for age, height, tracheal area, and smoking category the FVC and FEV1 for all exposed subjects were on average 7% v 6% less than predicted from the referents and twice as much for the subjects with the highest exposure. The four year declines in FVC and FEV1 were larger than in the referents, significantly so for FEV1. There were no significant correlations between pleural plaque and ventilatory function after adjustment for exposure. Thus the age adjusted reduction in ventilatory function had progressed during the follow up period despite the cessation of exposure and the lack of radiological signs of asbestosis.

Adult↗

Pulmonary fibrosis in asbestos insulation workers with lung cancer: a radiological and histopathological evaluation.

This study was undertaken to determine the relation between radiographic and histological manifestations of pulmonary asbestosis (interstitial fibrosis) in insulation workers who had died of lung cancer. Of 450 confirmed deaths from lung cancer a chest radiograph suitable for determining evidence of pneumoconiosis was obtained in 219. Of these cases, 138 also had a tissue specimen submitted that was suitable for histological study to determine the extent of histological fibrosis. There was a significant albeit limited correlation between the radiographic and histological findings (r = 0.27, p less than 0.0013). All 138 cases had histological evidence of parenchymal fibrosis; in 25 (18%), however, there was no radiographic evidence of parenchymal fibrosis. In 10 cases (7%) both parenchymal and pleural disease were undetectable on the radiograph. Thus a negative chest radiograph does not exclude the presence of interstitial fibrosis (asbestosis) in a substantial proportion of insulation workers previously exposed to asbestos who develop lung cancer.

Asbestos↗

Abnormal pulmonary function associated with diaphragmatic pleural plaques due to exposure to asbestos.

Pulmonary function was measured in 79 men with diaphragmatic pleural plaques (DPP) as the only abnormality characteristic of asbestos disease on chest radiographs. They were selected from 4572 construction and shipyard workers exposed to asbestos. Abnormalities of pulmonary function in 21 non-smokers and 43 current smokers were compared with referent values adjusted for height, age, and duration of cigarette smoking. In the non-smokers, flows (FEV1) FEF75-85 and FEV1/FVC) were reduced and TGV and RV/TGV were raised. Current smokers had similar significant reductions. Thus by contrast with some current opinion that plaques are "an index only of past asbestos exposure," workers with plaques, even limited to the diaphragm, have functional impairment typical of pulmonary asbestosis. This suggests that they have pulmonary asbestosis, which is below the threshold of radiographic recognition.

Aged↗

Study of occupational lung cancer in asbestos factories in China.

A retrospective cohort study (1972-81) of occupational cancers in asbestos (chrysotile) factories has been previously published. In this paper the results of continued tracing and interviewing of members of this cohort from 1982 to 1986 is reported. The cohort included 5893 persons (45,974 person-years for men and 39,445 person-years for women). Malignant tumours played a large part in causes of death (36.9%). There were 183 cancers and 67 lung cancers among 496 deaths. The mortality due to lung cancer had a tendency to increase. By comparison with a control group, the RR of lung cancer was 5.32 (p < 0.01), and the SRR of lung cancer was 4.2 (p < 0.01), significantly higher than those of a control group. Among 148 cases of death from asbestosis there were 33 cases complicated with lung cancer (22.3%). The dose-response relations between exposure to asbestos and incidence of asbestosis and lung cancer were also studied in one asbestos factory. There was a positive correlation. A synergistic effect was found between cigarette smoking and lung cancer. Preventive and control measures and exposure limits for asbestos dust in the air of workplaces were recommended.

Asbestos, Serpentine↗

Relation of spirometric function to radiographic interstitial fibrosis in two large workforces exposed to asbestos: an evaluation of the ILO profusion score.

OBJECTIVES: To analyse quantitatively the relations of spirometric lung function (forced vital capacity (FVC)) to radiographic interstitial pulmonary fibrosis (assessed by the International Labour Organisation (ILO) profusion score of small irregular opacities) in two large workforces exposed to different intensities of asbestos. These analyses consider the question whether a similar profusion score n differently exposed workers is associated with a similar effect on lung function. METHODS: Surveys of two workforces, insulators (n = 2611) and sheet metal workers (n = 1245), by the same investigators allowed comparison of the effects of the two levels of exposure to asbestos. The two groups were of similar age and had similar percentages of non-smokers and smokers. All radiographs were read by the same expert reader. RESULTS: Consistent with their less continuous and less intense exposure to asbestos, metal workers had: (a) far less frequent radiographic asbestosis (profusion score > or = 1/0, 17.5% v 59.6% for insulators): (b) less severe radiographic asbestosis (only 1.1% had scores > or = 2/1 v 13.3% of insulators); (c) a similar slope to that seen in insulators for the relation between FVC and profusion score when pleural thickening was absent; (d) less frequent pleural fibrosis (36% v 75%); and (e) less frequent restrictive impairment (23% v 33%). In both insulators and metal workers, lung function was below normal even when lung fields were normal, FVG fell with increasing profusion, it was lower in smokers and in those with pleural thickening at comparable profusion scores, and these was no difference in FVC between scores 0/1 and 1/0. CONCLUSION: The decrease in FVC with increasing profusion score in both workforces as well as the similar slopes for the relation between FVG and profusion score and the similar FVG at similar scores in the absence of pleural thickening confirm the ILO profusion score as an acceptable assessment of pulmonary fibrosis.

Adult↗

Increased serum concentrations of growth factor receptors and Neu in workers previously exposed to asbestos.

OBJECTIVES: Epidermal growth factor receptor (EGFR) and oncogene Neu belong to a family of growth factor receptors which may play a part in carcinogenesis. Although increased serum concentrations of Neu and EGFR have been shown in several patients with asbestosis who later developed cancer, serum concentrations have not been studied in workers exposed in the past to asbestos but without asbestos related diseases. METHODS: Serum concentrations of secreted growth factor receptors were studied in 300 workers exposed in the past to asbestos and the results were compared with those of 70 controls. RESULTS: In the controls 4.3% (3/70) had EGFR values > 912 units/ml, compared with 39% (117/299) of the exposed group (p < 0.001). The difference in high values was even more pronounced for Neu with 4.3% of controls having Neu values > 2580 fmol/ml compared with 72% (216/299) of the exposed workers (p < 0.001). Pleural plaques predicted lower serum concentrations of EGFR but not lower Neu concentrations, and this finding remained significant after adjustment for age, exposure time, smoking, and time from initial exposure. CONCLUSIONS: Enhanced secretion of EGFR and Neu was found in a large cohort of retired asbestos workers with a wide range of exposure and latency periods. They did not have asbestosis or cancer and their EGFR values were higher in those without plaques. Further studies are needed to confirm our results, to determine the source of the secreted growth factor receptors, and to study their possible value as risk factors in the development of cancer.

Adult↗

Redistribution of pulmonary EC-SOD after exposure to asbestos.

Inhalation of asbestos fibers leads to interstitial lung disease (asbestosis) characterized by inflammation and fibrosis. The pathogenesis of asbestosis is not fully understood, but reactive oxygen species are thought to play a central role. Extracellular superoxide dismutase (EC-SOD) is an antioxidant enzyme that protects the lung in a bleomycin-induced pulmonary fibrosis model, but its role has not been studied in asbestos-mediated disease. EC-SOD is found in high levels in the extracellular matrix of lung alveoli because of its positively charged heparin-binding domain. Proteolytic removal of this domain results in clearance of EC-SOD from the matrix of tissues. We treated wild-type C57BL/6 mice with 0.1 mg of crocidolite asbestos by intratracheal instillation and euthanized them 24 h later. Compared with saline- or titanium dioxide-treated control mice, bronchoalveolar lavage fluid (BALF) from asbestos-treated mice contained significantly higher total protein levels and increased numbers of inflammatory cells, predominantly neutrophils, indicating acute lung injury in response to asbestos. Decreased EC-SOD protein and activity were found in the lungs of asbestos-treated mice, whereas more EC-SOD was found in the BALF of these mice. The EC-SOD in the BALF was predominantly in the proteolyzed form, which lacks the heparin-binding domain. This redistribution of EC-SOD correlated with development of fibrosis 14 days after asbestos exposure. These data suggest that asbestos injury leads to enhanced proteolysis and clearance of EC-SOD from lung parenchyma into the air spaces. The depletion of EC-SOD from the extracellular matrix may increase susceptibility of the lung to oxidative stress during asbestos-mediated lung injury.

Animals↗

Interstitial pulmonary fibrosis induced in hamsters by intratracheally administered chrysotile asbestos. Histology, lung mechanics, and inflammatory events.

The development of interstitial pulmonary fibrosis (IPF) is associated with persistent cellular infiltration and progressive connective tissue accumulation in the alveolar walls. To develop and characterize an animal model of IPF in which pulmonary fibrosis evolves slowly, as well as to develop an inexpensive, easily produced, model of asbestosis, Syrian golden hamsters received single intratracheal injections of either UICC chrysotile asbestos or saline. Animals were then examined at time points up to 180 days for pulmonary histologic and physiologic changes, cytologic characteristics of cells recovered by bronchoalveolar lavage, and spontaneous release of neutrophil chemoattractant activity by alveolar macrophages. Within days after asbestos treatment, hamsters developed a patchy bronchopneumonia centered around terminal airways, which progressed peripherally with time to involve the alveolar walls with persistent inflammation and the gradual development of interstitial and peribronchiolar fibrosis. These histologic changes were accompanied by physiologic findings of air-flow obstruction with air trapping. Bronchoalveolar lavage revealed a persistent neutrophilia that began within 24 h of asbestos treatment; this was associated with the spontaneous release of neutrophil chemotactic activity by cultured alveolar macrophages. In this animal model, pulmonary inflammation and fibrosis can be predictably produced by a single intratracheal instillation of chrysotile asbestos. It represents a useful tool for studying both asbestosis and pulmonary fibrosis in general.

Animals↗

Talc: understanding its manifestations in the chest.

Four distinct forms of pulmonary disease caused by talc have been defined. The first form, talcosilicosis, is caused by talc mined with high-silica-content mineral. Findings in this form are identical with those of silicosis. Talcoasbestosis closely resembles asbestosis and is produced by crystalline talc, generally inhaled with asbestos fibers. Pathologic and radiographic abnormalities are virtually identical with those of asbestosis, including calcifications and malignant tumor formation. The third form, talcosis, caused by inhalation of pure talc, may include acute or chronic bronchitis as well as interstitial inflammation; radiographically, it appears as interstitial reticulations or small, irregular nodules, typical of small-airway obstruction. The fourth form, due to intravenous administration of talc, is usually associated with abuse of oral medications and production of vascular granulomas manifested by consolidations, large nodules, and masses. Radiographic abnormalities associated with talc can be predicted when there is sufficient history of the nature of exposure, including the region of origin of the talc in cases of inhalation. Radiographic changes, such as diaphragmatic plaques, often attributed to both talc and asbestos have not been documented to be caused by talc alone. The author provides review of 18 well-documented cases.

Adult↗

A patient with asbestos-induced lung cancer complicated by silicosis.

A 76-year-old male died of lung cancer. At first, he was diagnosed as a silicosis, because he had worked for 30 years as a caster in shipyard and large opacities detected by chest x-ray and CT scanning. After the operation of lung cancer, numerous asbestos bodies were observed in the operated lung tissues. The detailed occupational inquiry revealed his asbestos use as a caster in shipyard. Early stage of asbestosis was suspected by chest CT scanning, but not definitely diagnosed in premortal examinations. Asbestosis, pleural plaques, silicosis and large cell carcinoma of the lung were histopathologically confirmed at the autopsy. A patient with asbestos-induced lung cancer complicated by silicosis was rarely published in the literature.

Aged↗

The effects of asbestos on macrophages.

The exact role of the alveolar macrophage in the pathogenesis of asbestosis is not known. Most studies of the effect of asbestos on macrophages have been concerned with the in vitro biochemical or cytotoxic properties of the dust and have made use of peritoneal macrophages. In general, chrysotile had a toxic effect on the macrophages, whereas amphibole varieties did not. Most forms of absetos, however, are actively fibrogenic in man and animals, and there is no clear correlation between in vitro cytotoxicity of various forms of asbestos and their fibrogenicity. Recent experiments in which animals are exposed to asbestos in vivo provide evidence of alteration of macrophage activity, as demonstrated by changes in surface morphology and IgG receptor sites, as well as released of various secretory products. Deposition of complement components found on the surface of alveolar marcophages from animals exposed to asbestos could be a manifestation of a humoral immune response directed against an altered cell. The capacity of macrophages to participate in inflammation, tissue repair, and immunity suggests an immunopathogenic concept for the development of asbestosis.

Animals↗

Interspecies comparisons of lung responses to inhaled particles and gases.

Two important challenges for inhalation toxicologists involve the elucidation of mechanisms of lung toxicity caused by inhalation of chemicals or particulate materials, as well as the extrapolation of animal data to humans. Because risk estimates of toxicity generally are dependent upon experimental data for which a variety of species are utilized, a fundamental knowledge of species similarities and differences in lung anatomy, physiology, biochemistry, cell biology, and corresponding disease processes is essential. In the present review, the known mechanisms of particle deposition and clearance among various species have been highlighted and related to structure/function relationships and pathogenetic responses to some selected inhaled toxicants. In the aggregate, there is remarkable homogeneity in form and function among the species. Morphologic aspects of the respiratory tract and lung defense mechanisms are qualitatively similar among species. On the other hand, quantitative differences between humans and experimental animals are known to exist with respect to deposition and mucociliary clearance of inhaled particulates, and these factors are likely to influence the dose that is delivered to specific target sites in the lung. It is interesting to consider that pathologic cellular events following asbestos, ozone, and nitrogen dioxide exposure are likely to occur at similar sites in humans, nonhuman primates, and rodents. In this respect, it has been demonstrated that the early lesions of asbestos-induced lung disease in both rats and humans are initiated at similar anatomical sites, i.e., the junctions of terminal airways and alveolar regions. PMs and complement-mediated mechanisms have been implicated in the development of asbestosis in rats; however, it remains to be determined whether complement activation plays an important role in human asbestosis, although pulmonary and interstitial macrophages clearly are associated with the fibrogenic process associated with this restrictive lung disease. The toxic pulmonary effects following ozone exposure have been well studied in rodents and nonhuman primates. It has been established that distal airway and alveolar epithelial cells are principal targets of oxidant pollutants, and this is well supported by dosimetry considerations, morphologic observations, and morphometric analyses. Chronic ozone exposure in rats and monkeys causes epithelial injury at the level of the terminal bronchiole and proximal alveolar regions of the lung.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Inhalation↗

[High resolution computerized tomography in the diagnosis of silicosis and mixed dust pneumoconiosis].

The clinical observation, the work history, the analysis of pulmonary function tests and, mainly, the conventional x-ray chest radiograms have represented, til now, the diagnostic basis for pneumoconiosis (silicosis, mixed dust pneumoconiosis, asbestosis). Recently, the high resolution chest tomography (HRCT) has been introduced into the diagnostic procedures: such method seems to have its main application in the assessment of incipient clinical pictures of pneumoconiosis, particularly when characterized by normal pulmonary function tests. 75 silica- and mixed dust exposed workers were submitted to both radiologic methods. The great majority of them had already been recognized to be affected by asbestosis. The statistical analysis (Cohen K) showed a satisfactory agreement between radiographic and tomographic I.L.O. classes. However, high resolution tomography appeared to be more accurate in the assessment of less severe clinical pictures. In conclusion, we underline the importance of high resolution chest tomography in the evaluation of individual clinical cases, particularly when forensic problems are involved.

Adult↗

Respiratory conditions in Malaysian asbestos cement workers.

A cross-sectional study was conducted to determine the prevalence and type of respiratory conditions including asbestos-related diseases among Malaysian asbestos cement workers. The study population consisted of 1164 workers who had undergone medical surveillance from 1995 to 1997, including full history, physical examination, chest radiography and spirometry. More than half the male workers were smokers or ex-smokers, with smokers having more respiratory symptoms and signs, and reduced FEV1 compared with non smokers. The five most common respiratory conditions diagnosed were bronchial asthma, chronic bronchitis, pulmonary tuberculosis, upper respiratory tract infections and allergic rhinitis. On follow-up, there were also two cases of asbestosis and one case of bronchial carcinoma. The asbestosis cases were probably related to heavy occupational exposure to asbestos fibres in the past, before governmental regulations were gazetted in 1986. Further follow-up is essential for continued monitoring of the health status of asbestos workers.

Adolescent↗

Expression of antioxidant enzymes in rat lungs after inhalation of asbestos or silica.

Several studies indicate that active oxygen species play an important role in the development of pulmonary disease (asbestosis and silicosis) after exposure to mineral dust. The present study was conducted to determine if inhaled fibrogenic minerals induced changes in gene expression and activities of antioxidant enzymes (AOE) in rat lung. Two different fibrogenic minerals were compared, crocidolite, an amphibole asbestos fiber, and cristobalite, a crystalline silicon dioxide particle. Steady-state mRNA levels, immunoreactive protein, and activities of selected AOE were measured in lungs 1-10 days after initiation of exposure and at 14 days after cessation of a 10-day exposure period. Exposure to asbestos resulted in significant increases in steady-state mRNA levels of manganese-containing superoxide dismutase (MnSOD) at 3 and 9 days and of glutathione peroxidase at 6 and 9 days. An increase in steady-state mRNA levels of copper, zinc-containing superoxide dismutase (CuZnSOD), was observed at 6 days. Exposure to asbestos also resulted in overall increased enzyme activities of catalase, glutathione peroxidase and total superoxide dismutase in lung. In contrast, silica caused a dramatic increase in steady-state levels of MnSOD mRNA at all time periods and an increase in glutathione peroxidase mRNA levels at 9 days. Activities of AOE remained unchanged in silica-exposed lungs. In both models, increases in gene expression of MnSOD correlated with increased amounts of MnSOD immunoreactive protein in lung and the pattern and extent of inflammation. These data indicate that the profiles of AOE are dissimilar during the development of experimental asbestosis or silicosis and suggest different mechanisms of lung defense in response to these minerals.

Animals↗

[Quantitative analysis of pneumoconiosis in standard chest radiographs].

A computerized method to quantify and characterize interstitial diseases by using physical texture measures obtained from an analysis of the power spectrum of lung textures in digital chest radiographs was applied to Japanese standard radiographs of pneumoconiosis. Texture measures were determined from standard radiographs of silicosis, asbestosis, and other types of pneumoconiosis as well as chest radiographs of normal lungs. Our preliminary results indicated that the texture measures obtained from computer analysis corresponded closely with the standard categories of silicosis. However, there was no significant correlation between texture measures and the categories for asbestosis and other types of pneumoconiosis in terms of texture pattern. Japanese standard radiographs of pneumoconiosis are categorized according to the profusion of opacities, without reference to the size and shape of the opacities. Furthermore, in some films the size and shape of the opacities vary considerably within the same category. Therefore, it is considered that these characteristics of the standard films affected the results of our texture measures. It also considered that a large ROI and other texture measures are needed to characterize large opacities and mixed-shaped opacities of pneumoconiosis.

Humans↗